Hábitos de consumo de medicamentos de venta libre por estudiantes del área de la salud en Cartagena-Colombia / Over-the-counter medication consumption habits in health students from Cartagena-Colombia / Hábitos de consumo de medicamentos isentos de prescrição por estudantes de saúde em Cartagena-Colômbia

Introducción: Los medicamentos de venta libre (OTC por su sigla en inglés Over The Counter), son ampliamente usados por la mayoría de las personas a nivel mundial, sin embargo, solamente son usados de forma responsable en países donde existe una farmacia comunitaria profesional legalizada. Objetivo: Describir los hábitos de consumo de medicamentos de venta libre por estudiantes universitarios del área de la salud. Materiales y métodos: Estudio descriptivo transversal, desarrollado en tres universidades de Cartagena. Se aplicó un instrumento tipo encuesta a 140 estudiantes acerca de hábitos de consumo y conocimiento sobre OTC, creencias, actitudes y prácticas. Resultados: El cuestionario presentó una consistencia interna alta con Alfa de Cronbach'sde 0,77. El 59% fueron mujeres, las en edades entre 16-30 años, el 91% estuvo de acuerdo que la automedicación es perjudicial. Sin embargo, 61% asegura automedicarse porque los padecimientos son menores y frecuentes. Los medicamentos de mayor consumo, fueron el acetaminofén 52,9% y los medicamentos antiinflamatorios no esteroides (AINES) con 16,48%, incluyeron en sus respuestas medicamentos de no venta libre. Conclusión: Los estudiantes son conscientes del riesgo de la automedicación, sin embargo, la practican de forma frecuente. Muchos reportaron consumo de medicamentos como amitriptilina, antibióticos, opiáceos, furosemida y corticoides.

Introduction: Over-the-counter (OTC) medications are widely used worldwide, however they are responsibly used only in countries with legalized professional community pharmacies. Objective:To describe over-the-counter medication use habits in university students from health programs. Materials and methods:Descriptive cross-sectional study carried out in three universities from Cartagena. A survey-type instrument was applied to 140 students, asking about their use habits and knowledge regarding OTC, beliefs, attitudes and practices. Results:The questionnaire showed a high internal inconsistency, with a Cronbach's alpha of 0.77. 59% of participants were women aged between 16 to 30 years old and 91% agreed that self-medication is harmful. Nevertheless, 61% self-medicated because of minor and frequent conditions. OTC medications with the highest use were acetaminophen (52.9%) and NSAIDs (16.48%). Conclusions:Even though students are aware of the self-medication risks, they still practice it frequently. Many participants reported the use of medications such as amitriptyline, antibiotics, opioids, furosemide, and corticosteroids.

Introdução:Os medicamentos isentos de prescrição (OTCOver The Counter) são amplamente utilizados pela maioria das pessoas em todo o mundo, porém somente são usados de forma responsável em países onde existe uma farmácia comunitária profissional legalizada. Objetivo: Descrever os hábitos de consumo de medicamentos isentos de prescrição por universitários da área da saúde. Materiais e métodos: Estudo descritivo transversal, desenvolvido em três universidades de Cartagena. Foi aplicado um instrumento do tipo inquérito a 140 alunos sobre hábitos de consumo e conhecimentos sobre OTC, crenças, atitudes e práticas. Resultados: O questionário apresentou alta consistência interna com Alfa de Cronbach ́sde 0,77. 59% eram mulheres, com idades entre 16 e 30 anos, 91% concordaram que a automedicação é prejudicial. No entanto, 61% dizem que se automedicam porque os males são leves e frequentes. Os medicamentos de maior consumo foram o acetaminofeno 52,9% e os anti-inflamatórios não esteroidais com 16,48%, incluindo medicamentos isentos de prescrição em suas respostas. Conclusão: Os alunos estão cientes do risco da automedicação, porém isto é praticado com frequência. Muitos relataram consumo de medicamentos como amitriptilina, antibióticos, opioides, furosemida e corticosteroides.

Prospective Protective Effects of Arthrospira platensis Against Acetaminophen Induced Hepato-Renal Toxicity in Rats / Efectos Protectores Prospectivos de Arthrospira platnesis Contra la Toxicidad Hepatorrenal Inducida por Paracetamol en Ratas

SUMMARY: The toxic effects of acetaminophen appear primarily in the liver and kidney. The protective effect of blue green alga Arthrospira platensis on hepato-renal toxicity caused by acetaminophen was evaluated in male rats. The obtained results showed that subcutaneous injection of acetaminophen at a dose 120 &240 սl acetaminophen/kg by weight resulted in an observed elevation in the enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Alkaline phosphatase (ALP), serum total lipids, total cholesterol, creatinine, total bilirubin, urea, nitric oxide (NO), L- malondialdehyde (MDA) and interleukins (IL-2 &IL-6). However, there is a decrease in the serum total protein, albumin and loss in antioxidant enzyme activities in liver including; superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSH). This effect was found to be dose and time dependent. In spite of, pre- oral administration of Arthrospira platensis 1000 mg/kg .b. wt. prior acetaminophen injection succeeded to modulate the effect of the observed abnormalities caused by acetaminophen. Moreover, there were no remarkable changes in serum biomarkers of rats received Arthrospira platensis only at a dose of 1000 mg/kg by weight (group 2). The histopathological findings confirm the biochemical results that indicates the safety use of Arthrospira platensis at the selected dose in this study. Therefore, the present results clarified the protective effect of blue green alga Arthrospira platensis on oxidative stress, hepatic and nephrotoxicity induced by acetaminophen in male Wister rats.

Los efectos tóxicos del paracetamol aparecen principalmente en el hígado y el riñón. Se evaluó en ratas macho Wistar el efecto protector del alga verde azulada Arthrospira platensis sobre la toxicidad hepatorrenal causada por paracetamol. Los resultados obtenidos mostraron que la inyección subcutánea de paracetamol a dosis de 120 y 240 µl de paracetamol/kg, resultó en una elevación en las actividades enzimáticas de la aspartato aminotransferasa (AST), alanina aminotransferasa (ALT) y fosfatasa alcalina (ALP), lípidos séricos totales, colesterol total, creatinina, bilirrubina total, urea, óxido nítrico (NO), L- malondialdehído (MDA) e interleucinas (IL-2 e IL-6). Sin embargo, hay una disminución en la proteína sérica total, albúmina y pérdida en las actividades de las enzimas antioxidantes en el hígado, incluyendo; superóxido dismutasa (SOD), catalasa (CAT) y glutatión reductasa (GSH). Se encontró que este efecto era dependiente de la dosis y el tiempo. A pesar de la administración preoral de Arthrospira platensis 1000 mg/kg, la inyección previa de acetaminofeno logró modular el efecto de las anormalidades observadas causadas por el acetaminofeno. Además, no hubo cambios notables en los biomarcadores séricos de ratas que recibieron Arthrospira platensis solo a una dosis de 1000 mg/kg (Grupo 2). Los hallazgos histopatológicos confirman los resultados bioquímicos que indican la seguridad del uso de Arthrospira platensis a la dosis seleccionada en este estudio. Por lo tanto, los presentes resultados aclararon el efecto protector del alga verde azulada Arthrospira platensis sobre el estrés oxidativo, la toxicidad hepática y la nefrotoxicidad inducida por paracetamol en ratas Wistar macho.

Múltiples reacciones adversas graves a fármacos en un paciente luego de la infección por COVID-19: informe de un caso / Drug-induced severe cutaneous adverse reactions in a patient after COVID-19 infection: case report

Durante la pandemia por COVID-19 se observaron diversas reacciones adversas a fármacos. Esto pudo haber estado relacionado con una mayor susceptibilidad inmunológica de los pacientes con SARS-CoV-2 a presentar este tipo de cuadros, así como también con la exposición a múltiples medicamentos utilizados en su tratamiento. Comunicamos el caso de un paciente con una infección respiratoria grave por COVID-19, que presentó 2 reacciones adversas graves a fármacos en un período corto de tiempo. (AU)

During the COVID-19 pandemic, various adverse drug reactions were observed. This could have been related to a greater immunological susceptibility of patients with SARS-CoV-2 to present this type of symptoms, as well as exposure to multiple drugs used in their treatment. We report the case of a patient with a severe respiratory infection due to COVID-19, who presented 2 serious adverse drug reactions associated with paracetamol in a short period of time. (AU)

Quercetin and resveratrol are associated with the downregulation of TNFalpha/NF-kB/inos axis-mediated acute liver injury in rats induced by paracetamol poisoning / La quercetina y el resveratrol están asociados con la regulación decreciente de la lesión hepática aguda mediada por el eje TNF-alfa/NF-kB/inos en ratas inducida por envenenamiento con paracetamol

SUMMARY: Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

El envenenamiento por paracetamol (conocido como acetaminofeno o APAP) causa daño hepático agudo que puede provocar una insuficiencia orgánica y la muerte. El objetivo de este trabajo fue determinar si la sobredosis de APAP puede aumentar la hepatotoxicidad mediada por el eje del factor de necrosis tumoral alfa (TNF-α)/factor nuclear kappa B (NF-kB)/óxido nítico sintasa inducida (iNOS) en ratas, y si el polifenólico antiinflamatorio compuesto por quercetina (QUR) más resveratrol (RES) pueden mejorar estos parámetros. Por lo tanto, inducimos hepatotoxicidad aguda en ratas usando una sobredosis de APAP (2 g/kg, por vía oral). El grupo protector de ratas se trató con 50 mg/ kg de QUR más 30 mg/kg de RES durante una semana antes de la ingestión de APAP. Los animales se sacrificaron el día 8. El envenenamiento con APAP en el tejido hepático provocó la inducción de niveles de TNF-α, NF-kB e iNOS, que se redujeron significativamente (p<0,05) con QUR+RES. QUR+RES, también inhibió los biomarcadores de daño hepático, la alanina aminotransferasa (ALT) y el aspartato aminotransferasa (AST). Además, se observó una relación entre la lesión hepática y la hepatotoxicidad mediada por el eje TNF-α /NF-kB/iNOS. Por lo tanto, los datos presentados respaldan la conclusión de que la intoxicación por paracetamol aumenta la hepatotoxicidad mediada por el eje TNF-α /NF-kB / iNOS, y está protegida por una combinación de quercetina y resveratrol.

Sobredosis de acetaminofén y comportamientos relacionados con suicidio / Acetaminophen overdose and suicide-related behaviors / Overdose de paracetamol e comportamentos suicidas

Objetivo: este trabajo busca caracterizar el comportamiento relacionado con el suicidio en la población admitida al Hospital San Vicente Fundación, Rionegro, con sobredosis de acetaminofén entre enero 2019 y diciembre 2020 y detectar factores asociados con la dosis tóxica. Metodología: análisis descriptivo con información obtenida de historias clínicas. Resultados: 63 individuos presentaron ingestión aguda de dosis tóxica de acetaminofén como comportamiento relacionado con suicidio. Cuarenta y tres eran mujeres, 60% tenía antecedente de enfermedad psiquiátrica, 35% reportó al menos un intento suicida previo y 22% consumieron 25g o más. La lesión hepática aguda se asoció con una dosis tóxica. Conclusiones: evidenciamos una alta prevalencia de antecedente de enfermedad psi­quiátrica y comportamiento relacionado con suicidio y casi un tercio de los pacientes ingirió dosis mayores al umbral de riesgo para falla hepática. Además, la impulsividad e ingesta en casa sugiere que políticas públicas restrictivas pueden no impactar en la reducción de estos eventos en la población.

Objective: this work seeks to characterize the behavior related to suicide in the po­pulation admitted to the Hospital San Vicente Fundación, Rionegro, with an overdose of acetaminophen between January 2019 and December 2020, and to identify factors associated with the toxic dose. Methodology: descriptive analysis with information obtained from medical records. Results: 63 individuals presented acute ingestion of a toxic dose of acetaminophen as behavior related to suicide. Forty-three were women, 60% had a history of psychiatric illness, 35% reported at least one previous suicide attempt, and 22% consumed 25g or more. Acute liver injury was associated with a toxic dose. Conclusions: we evidenced a high prevalence of a history of psychiatric illness and beha­vior related to suicide; almost a third of the patients ingested doses greater than the risk threshold for liver failure. In addition, impulsiveness and eating at home suggests that res­trictive public policies may not have an impact on reducing these events in the population.

Objetivo: Este trabalho busca caracterizar o comportamento relacionado ao suicídio na população internada no Hospital San Vicente Fundación, Rionegro, com overdose de acetaminofeno entre janeiro de 2019 e dezembro de 2020 e detectar fatores associados à dose tóxica. Metodologia: análise descritiva com informações obtidas dos prontuários. Resultados: 63 indivíduos apresentaram ingestão aguda de dose tóxica de paracetamol como comportamento relacionado ao suicídio. Quarenta e três eram mulheres, 60% tinham histórico de doença psiquiátrica, 35% relataram pelo menos uma tentativa de suicídio anterior e 22% consumiram 25g ou mais. A lesão hepática aguda foi associada a uma dose tóxica. Conclusões: evidenciamos alta prevalência de história de doença psiquiátrica e com-portamento relacionado ao suicídio e quase um terço dos pacientes ingeriu doses superiores ao limiar de risco para insuficiência hepática. Além disso, a impulsividade e a alimentação em casa sugerem que políticas públicas restritivas podem não ter impacto na redução desses eventos na população.

Effectiveness of resveratrol as a hepatoprotector in a rat model of paracetamol-induced liver injury / Eficácia do resveratrol como hepatoprotetor em modelo de rato com lesão hepática induzida por paracetamol

Objective: Evaluate the effectiveness of resveratrol as a hepatoprotector in a rat model of paracetamol-induced liver injury and its biodistribution to understand its pharmacokinetics. Methodology: As an experimental approach, animals were divided into the test group with 4 subgroups and the control group with 4 subgroups. Animals of the "treated" group were subjected to resveratrol pre-treatment for eight days, followed by intoxication with a high dose of paracetamol on the 8th day. Animals were euthanized to collect the blood and liver tissue samples 24 and 72 h after the last administration. Hepatoprotective activity was evaluated through serum levels of glycogen and hepatic enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), histological and morphometric analysis of the liver tissue. For biodistribution analysis, different organs (organs, kidneys, heart and lungs) were collected and macerated, and resveratrol was quantified using high-performance liquid chromatography. Statistical analyses of morphometry, transaminases and alkaline phosphatase measurements, and biodistribution results were performed using GraphPad Prism® 3.0. Differences between groups were compared using ANOVA, followed by the Bonferroni test. Statistical significance was set at p < 0.05. Results: Resveratrol has a hepatoprotective action against acute intoxication by paracetamol, as evidenced by the histological decrease in necrosis and inflammatory foci, preservation of glycogen and other 1,2-glycols in zone 3, and reduction of serum ALT and AST levels. An increased presence of collagen was observed in acinar zones 1 and 3 with picrosirius red staining; therefore, quantification was performed in these regions showing smaller collagen areas in the R and RP groups than in the PC and NC groups Paracetamol caused a significant reduction in the resveratrol concentration in serum and the organs studied, indicating that the antioxidant activity of resveratrol is related to its hepatoprotective action. Conclusion: Resveratrol has hepatoprotective properties and can mitigate some of the liver damage caused by high doses of paracetamol, as indicated by changes in tissue characteristics and liver enzyme levels.

Objetivo: Avaliar a eficácia do resveratrol como hepatoprotetor em modelo de rato com lesão hepática induzida por paracetamol e sua biodistribuição para compreender sua farmacocinética. Metodologia: Como abordagem experimental, os animais foram divididos em grupo teste com 4 subgrupos e grupo controle com 4 subgrupos. Os animais do grupo "tratado" foram submetidos ao pré-tratamento com resveratrol durante oito dias, seguido de intoxicação com alta dose de paracetamol no oitavo dia. Os animais foram eutanasiados para coleta de amostras de sangue e tecido hepático 24 e 72 horas após a última administração. A atividade hepatoprotetora foi avaliada através dos níveis séricos de glicogênio e de enzimas hepáticas, como aspartato aminotransferase (AST), alanina aminotransferase (ALT) e fosfatase alcalina (ALP), análise histológica e morfométrica do tecido hepático. Para análise de biodistribuição, diferentes órgãos (órgãos, rins, coração e pulmões) foram coletados e macerados, e o resveratrol foi quantificado por cromatografia líquida de alta eficiência. Análises estatísticas de morfometria, medidas de transaminases e fosfatase alcalina e resultados de biodistribuição foram realizadas utilizando GraphPad Prism® 3.0. As diferenças entre os grupos foram comparadas por meio de ANOVA, seguida do teste de Bonferroni. A significância estatística foi estabelecida em p < 0,05. Resultados: O resveratrol tem ação hepatoprotetora contra a intoxicação aguda por paracetamol, evidenciada pela diminuição histológica da necrose e dos focos inflamatórios, preservação do glicogênio e outros 1,2-glicóis na zona 3 e redução dos níveis séricos de ALT e AST. Foi observada presença aumentada de colágeno nas zonas acinares 1 e 3 com coloração picrosirius red; portanto, foi realizada quantificação nessas regiões mostrando menores áreas de colágeno nos grupos tratados com resveratrol e resveratrol associado com paracetamol do que nos grupos controles positivo e negativo. O paracetamol causou redução significativa na concentração de resveratrol no soro e nos órgãos estudados, indicando que a atividade antioxidante do resveratrol está relacionada à sua ação hepatoprotetora. Conclusão: O resveratrol possui propriedades hepatoprotetoras e pode mitigar alguns dos danos hepáticos causados por altas doses de paracetamol, conforme indicado por alterações nas características dos tecidos e nos níveis de enzimas hepáticas.

Intoxicación intencional por paracetamol en adolescentes: un problema de salud creciente: a propósito de un caso / Intentional paracetamol poisoning in adolescents: a growing health problem: clinical case study / Intoxicação intencional por paracetamol em adolescentes: um problema de saúde crescente: relato de caso

La intoxicación por paracetamol de causa no intencional en niños pequeños, e intencional en adolescentes es un motivo de consulta cada vez más frecuente en los servicios de urgencia. La gravedad y el pronóstico de esta intoxicación están dados por el riesgo de falla hepática. Ante la sospecha de ingesta de paracetamol, se debe conocer el tiempo transcurrido, la cantidad de ingesta del fármaco, estimar la toxicidad de la dosis ingerida para predecir hepatotoxicidad, determinar las medidas de contaminación necesarias, dosificar paracetamol en sangre y evaluar la necesidad de administración de antídoto. Se describe el caso de una adolescente que con intención suicida presentó una intoxicación aguda por paracetamol con riesgo de daño hepático requiriendo decontaminación digestiva, administración de antídoto y abordaje interdisciplinario de sus problemas psicoemocionales.

Paracetamol intoxication due to an unintentional cause in young children, and intentional in adolescents, is an increasingly frequent cause for consultation in emergency services. The severity and prognosis of this poisoning is due to the risk of liver failure. Given the suspicion of paracetamol ingestion, the time passed since the ingestion, the amount of paracetamol ingested, the estimate of the dose ingested to predict hepatotoxicity, we must determine the necessary decontamination measures and the paracetamol dose in blood and evaluate the need to administer a paracetamol antidote. We describe the case of an adolescent who presented acute paracetamol poisoning with risk of liver damage resulting from a suicide attempt and who required digestive decontamination, antidote administration and an interdisciplinary approach to her psychological and emotional problems.

A intoxicação não intencional por paracetamol em crianças pequenas e a intoxicação intencional em adolescentes é um motivo cada vez mais comum de consulta em serviços de emergência. A gravidade e o prognóstico desse envenenamento são dados pelo risco de insuficiência hepática. Quando há suspeita de ingestão de paracetamol, o tempo decorrido desde que é ingerido, a quantidade de paracetamol ingerida, a estimação da dose ingerida para predizer hepatotoxicidade, utilizamse para determinar as medidas de contaminação necessárias, dosar paracetamol no sangue e avaliar a ne- cessidade de administração de antídoto. Descrevemos o caso de uma adolescente com intenção suicida que apresentou intoxicação aguda por paracetamol com risco de lesão hepática com necessidade de descontaminação digestiva, administração de antídoto e abordagem interdisciplinar de seus problemas psicoemocionais.

Investigation of antioxidant activity of ethanolic extract of the bark of Caesalpinia ferrea in Swiss mice exposed to paracetamol / Investigação da atividade antioxidante do extrato etanólico da casca de Caesalpinia ferrea em camundongos Swiss expostos ao paracetamol

Aims: it was evaluated the antioxidant effect of the ethanolic extract of Caesal-pinia ferrea bark in a model of oxidative stress induced by paracetamol (PCM). Methods: male Swiss mice were subdivided into four groups (control; PCM; PCM+extract; extract; n=8) in which a dose of paracetamol (250 mg.kg-1) was administered and after 3 hours the treatment with the extract (100 mg.kg-1/day) was administered for seven days, via gavage. Oxidative stress biomarkers were determined, such as catalase, glutathione-S-transferase, reduced gluta-thione, ascorbic acid, thiobarbituric acid reactive substances and carbonylated proteins of liver, kidneys and brain and plasma parameters through the dosage of glucose, cholesterol, triglycerides, aspartate aminotransferase and alanine aminotransferase. Results: the Caesalpinia ferrea extract was able to reverse the lipid and protein damage caused by the drug in the liver tissue and caused the same effect in the renal and brain tissues in the carbonylated proteins. The extract alone decreased liver glutathione-S-transferase and increased catalase and brain glutathione-S-transferase activity, in addition to lowering glucose and cholesterol, but without altering the triglycerides. Conclusions: it was possible to conclude that the ethanolic extract of the bark of Caesalpinia ferrea has a good antioxidant activity, probably due to dose of paracetamol in the samples investigated. However, more studies are needed for a better understanding of the effects of this extract compared to the effects found in this research

Objetivos: foi avaliado o efeito antioxidante do extrato etanólico da casca de Caesalpinia ferrea em modelo de estresse oxidativo induzido por paracetamol (acetaminofeno, PCM). Métodos: camundongos Swiss machos foram subdivididos em quatro grupos (controle; PCM; PCM+extrato; extrato; n=8) nos quais foi administrada uma dose de paracetamol (250 mg.kg-1) e após três horas foi administrado o tratamento com o extrato (100 mg.kg-1/ dia) por sete dias, via gavagem. Foram determinados biomarcadores de estresse oxidativo, como catalase, glutationa-S-transferase, glutationa reduzida, ácido ascórbico, substâncias reativas ao ácido tiobarbitúrico e proteínas carboniladas do fígado, rins e cérebro, além de parâmetros plasmáticos através da dosagem de glicose, colesterol, triglicerídeos, aspartato aminotransferase e alanina aminotransferase. Resultados: o extrato de Caesalpinia ferrea foi capaz de reverter os danos lipídicos e proteicos causados pela droga no tecido hepático, e também causou o mesmo efeito nos tecidos renal e cerebral nas proteínas carboniladas. O extrato sozinho diminuiu a atividade da glutationa-S-transferase hepática e aumentou a da catalase e glutationa-S-transferase cerebral, além de diminuir a glicose e o colesterol, mas sem alterar os triglicerídeos. Conclusões: foi possível concluir que o extrato etanólico da casca de Caesalpinia ferrea apresenta uma boa atividade antioxidante, provavelmente devido à presença de taninos, tendo em vista os danos causados pela alta dose de paracetamol nas amostras investigadas. Entretanto, mais estudos são necessários para um melhor entendimento dos efeitos deste extrato frente aos efeitos encontrados nesta pesquisa

Rapid determination of acetaminophen in plasma by LC-MS/MS / 中华劳动卫生职业病杂志

Objective: To establish a method for the rapid determination of acetaminophen (APAP) in human plasma by LC-MS/MS. Methods: The plasma samples were extracted by methanol and acetonitrile (1: 1) and purified directly. C(18) column was used for sample separation. The mobile phase were methanol (5 mmol/L ammonium acetate) and water (5 mmol/L ammonium acetate). Samples were analyzed by LC MS/MS with the electrospray ionization multi reaction monitoring (MRM) mode. Results: The calibration curves of APAP was linear in the concentration range of 0~10 mg/L, the correlation coefficient (r) was greater than 0.999 0. The relative standard deviation within and between batches was less than 10%. The recovery rate were 96.81%~101.7%. The detection limit of the method was 0.1 μg/L and the lower limit of quantification was 0.3 μg/L. Conclusion: This method has strong specificity, high sensitivity and reliable determination results. It is suitable for the rapid analysis of clinical plasma samples.

Discovery of miRNA and target signal molecules involved in inhibition of chlorogenic acid on N-acetyl-p-aminophenol-induced hepatotoxicity based on microRNA array / 中国中药杂志

This study aims to observe the effect of chlorogenic acid(CGA) on microRNA(miRNA) in the process of protecting against N-acetyl-p-aminophenol(APAP)-induced liver injury. Eighteen C57BL/6 mice were randomly assigned into a normal group, a model group(APAP, 300 mg·kg~(-1)), and a CGA(40 mg·kg~(-1)) group. Hepatotoxicity of mice was induced by intragastric administration of APAP(300 mg·kg~(-1)). The mice in the CGA group were administrated with CGA(40 mg·kg~(-1)) by gavage 1 h after APAP administration. The mice were sacrificed 6 h after APAP administration, and plasma and liver tissue samples were collected for the determination of serum alanine/aspartate aminotransferase(ALT/AST) level and observation of liver histopathology, respectively. MiRNA array combined with real-time PCR was employed to discover important miRNAs. The target genes of miRNAs were predicted via miRWalk and TargetScan 7.2, verified by real-time PCR, and then subjected to functional annotation and signaling pathway enrichment. The results showed that CGA administration lowered the serum ALT/AST level elevated by APAP and alleviate the liver injury. Nine potential miRNAs were screened out from the microarray. The expression of miR-2137 and miR-451a in the liver tissue was verified by real-time PCR. The expression of miR-2137 and miR-451a was significantly up-regulated after APAP administration, and such up-regulated expression was significantly down-regulated after CGA administration, consistent with the array results. The target genes of miR-2137 and miR-451a were predicted and verified. Eleven target genes were involved in the process of CGA protecting against APAP-induced liver injury. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment with DAVID and R language showed that the 11 target genes were enriched in Rho protein-related signal transduction, vascular patterning-related biological processes, binding to transcription factors, and Rho guanyl-nucleotide exchange factor activity. The results indicated that miR-2137 and miR-451a played an important role in the inhibition of CGA on APAP-induced hepatotoxicity.

Fixed and on-demand regimens of acetaminophen in periodontal surgery: randomized clinical trial

Aim: to evaluate the clinical efficacy of an acetaminophen analgesic by comparing its prescription in fixed versus ondemand schedules after periodontal surgery. The hypothesis of the study was that the fixed regimen would be more effective than the on-demand regimen for postoperative analgesics following periodontal surgery. Methods: An open randomized clinical trial was conducted. The 68 patients who needed total flap surgery to restore supracrestal tissue attachment or surgical treatment of periodontitis were randomized". Visual Analogue Scale was used to assess pain. The fixed group (n = 34) received 500 mg of acetaminophen every 4 hours for 2 days. The on-demand group (n = 34) was instructed to use the acetaminophen "as needed," at intervals of no less than 4 hours between doses. Ibuprofen was the rescue medication for both groups. Pain scores and medication use were recorded 2, 6, 12, 24 and 48 hours after the surgical procedure. The study was registered at the Brazilian Registry of Clinical Trials under RBR-7wv259. Results: The two groups did not differ in relation to the frequency or the intensity of pain in a 48-hour period (n=20 in the fixed group, and n=22 in the on-demand group), or even in the intention-to-treat (n=34 in each group). Individuals who experienced moderate to severe pain used rescue medication more frequently in both groups. No adverse events were reported. Conclusion: Both regimens were effective in controlling postoperative pain after periodontal surgery

Efficacy of opioids and non-opioid analgesics in the treatment of post procedure pain of burned patients: a narrative review

Abstract Introduction Burns are a common trauma that cause acute severe pain in up to 80% of patients. The objective of this narrative review is to evaluate the efficacy of opioids, non-steroidal anti-inflammatory drugs, paracetamol, gabapentinoids, ketamine, and lidocaine in the treatment of acute pain in burn victims. Methodology The databases explored were PubMed, Embase, ClinicalTrials, and OpenGrey. The included randomized, controlled clinical trials assessed the analgesic efficacy of these drugs on hospitalized patients, had no age limit, patients were in the acute phase of the burn injury and were compared to placebo or other analgesic drugs. Studies describing deep sedation, chronic opioid use, chronic pain, and patients taken to reconstructive surgeries were excluded. The Jadad scale was used to evaluate quality. Results Six randomized controlled clinical trials (397 patients) that evaluated the analgesic efficacy of fentanyl (n = 2), nalbuphine (n = 1), ketamine (n = 1), gabapentin (n = 1), and lidocaine (n = 1) to treat post-procedural pain were included. Fentanyl, nalbuphine, and ketamine were effective, while lidocaine was associated with a slight increase in reported pain and gabapentin showed no significant differences. Two studies were of high quality, one was of medium high quality, and three were of low quality. No studies on the efficacy of NSAIDs or paracetamol were found. Conclusion Evidence of efficacy is very limited. Fentanyl, nalbuphine, and ketamine seem to be effective for controlling acute pain in burn patients, whereas gabapentin and lidocaine did not show any efficacy.

Analgesic effect of continuous adductor canal block versus continuous femoral nerve block for knee arthroscopic surgery: a randomized trial

Abstract Background and objectives Anterior cruciate ligament reconstruction (ACLR) is one of the most frequently performed orthopedic procedures. The ability to perform ACLR on an outpatient basis is largely dependent on an effective analgesic regimen. The aim of the study was to compare the analgesic effect between continuous adductor canal block (cACB) and femoral nerve block (cFNB) during arthroscopy guided ACLR. Method In this prospective, randomized, controlled clinical trial, 60 ASA I/II patients for arthroscopic ACLR were recruited. Patients in Group I received cACB and those in Group II cFNB. A bolus dose of 20 cc 0.5% levobupivacaine followed by 0.125% 5 mL.h-1 was started for 24 hours. Rescue analgesia in the form of paracetamol 1 g intravenous (IV) was given. Parameters assessed were time of first rescue analgesia, total analgesic requirement in 24 hours, and painless range of motion of the knee (15 degrees of flexion to further painless flexion). Results The time-to-first postoperative analgesic request (hours) was earlier in Group II (14.40 ± 4.32) than Group I (16.90 ± 3.37) and this difference was statistically significant (p< 0.05). The cumulative 24-h analgesic consumption (paracetamol in g) was 0.70 ± 0.47 in Group I and 1.70 ± 0.65 in Group II (p< 0.001). The painless range of motion (degree) was 55.67 ± 10.40 in Group I and 40.00 ± 11.37 in Group II (p< 0.001). Conclusion The findings of this study suggest that continuous adductor canal block provides superior analgesia in patients undergoing arthroscopic ACLR when compared to continuous femoral nerve block.

Indicación de N-acetilcisteína en distintas formas de toxicidad por paracetamol / Indication of n-acetylcysteine in differents forms of paracetamol toxicity

Introducción: la hepatotoxicidad por paracetamol está relacionada con la formación del metabolito N-acetil-parabenzoquinoneimina (NAPQI) y su falta de detoxificación a través del glutatión, cuyas reservas se deplecionan en el contexto de una sobredosis. La administración de N-acetilcisteína (NAC) como sustancia dadora de grupos tioles (-SH) contribuye a la prevención del daño hepático que puede desarrollarse con dosis terapéuticas o tóxicas. Métodos: se comentan 5 casos de exposición a paracetamol en los cuales se administró NAC por alteración de la función hepática. La gravedad de los cuadros varió en función de las dosis y del tiempo de latencia hasta la consulta. Resultados: cuatro pacientes ingirieron una única dosis tóxica y una paciente recibió la dosis diaria máxima de paracetamol de 4000 mg/día durante 5 días. La paciente que consultó dentro de las 4 horas posteriores a la ingesta no presentó elevación de transaminasas. Todas las pacientes recibieron NAC y sus valores de enzimas hepáticas se normalizaron al momento del alta. Conclusión: la administración temprana de NAC puede ser útil para prevenir daño hepático tanto en ingestas de dosis tóxicas, como en casos de utilización de dosis terapéuticas máximas durante varios días. (AU)

Introduction: paracetamol hepatotoxicity is related to the formation of the metabolite N-acetyl-parabenzoquinoneimine (NAPQI) and its lack of detoxification through glutathione, whose reserves are depleted in paracetamol overdose. The administration of N-acetylcysteine (NAC) as a donor of sulfhydryl groups (-SH) can prevent liver damage that could even occur with therapeutic or toxic doses. Methods: 5 cases of exposure to paracetamol are discussed, in which NAC was administered due to impaired liver function. These manifestations presented different severity depending on the drug doses and the time until medical consultation. Results: four patients ingested single toxic doses and one patient received the maximum daily dose of paracetamol of 4000 mg/day for 5 days. The patient who consulted within 4 hours after ingestion did not present elevation of transaminases. All patients received NAC, with normal liver enzymes at discharge. Conclusion: the early administration of NAC may be useful to prevent liver damage both in toxic dose intakes and in cases of use of maximum therapeutic doses for several days. (AU)

Qual Deve Ser o Tratamento de Primeira Linha para o Fechamento de Persistência de Canal Arterial Hemodinamicamente Significativo em Bebês Prematuros? / What Should be the First-line Treatment for the Closure of Hemodynamically Significant Patent Ductus Arteriosus in Premature Infants?

Resumo Fundamento É importante saber qual medicamento usar como tratamento de primeira linha para fechar o duto. Objetivos O objetivo deste estudo é comparar a eficácia e os efeitos colaterais das formas intravenosas (IV) de ibuprofeno e paracetamol e contribuir para a literatura investigando o primeiro medicamento selecionado no tratamento clínico da persistência do canal arterial (PCA). Métodos Nosso estudo foi realizado entre janeiro de 2017 e dezembro de 2019. Foram incluídos no estudo bebês prematuros com peso ao nascer (PN) ≤1500 g e idade gestacional (IG) ≤32 semanas. No período do estudo, todos os bebês com persistência do canal arterial hemodinamicamente significativa (hsPCA) receberam ibuprofeno intravenoso (IV) como resgate como tratamento clínico primário ou tratamento com paracetamol IV se houvesse contraindicações para o ibuprofeno. Os pacientes foram divididos em dois grupos: pacientes que receberam ibuprofeno IV e pacientes que receberam paracetamol IV. Resultados Desses pacientes, 101 receberam paracetamol IV e 169 receberam ibuprofeno IV. A taxa de sucesso do fechamento da PCA com o primeiro curso do tratamento foi de 74,3% no grupo de paracetamol IV e 72,8% no grupo de ibuprofeno IV (p=0,212). Conclusões Nossos resultados mostram que o paracetamol IV é tão eficaz quanto o ibuprofeno IV no tratamento de primeira linha de hsPCA, podendo se tornar o tratamento preferencial para o controle de hsPCA.

Abstract Background It is important which medicine to use as a first-line treatment to close the duct. Objectives The aim of this study is to compare the effectiveness and side effects of intravenous (IV) forms of ibuprofen and paracetamol and to contribute to the literature investigating the first drug selected in the medical treatment of patent ductus arteriosus (PDA). Methods Our study was conducted between January 2017 and December 2019. Premature infants with birth weight (BW) ≤1500 g and gestational age (GA) ≤32 weeks were included in the study. In the study period, all infants with hemodynamically significant patent ductus arteriosus (hsPDA) were given rescue intravenous (IV) ibuprofen as a primary medical treatment or IV paracetamol treatment if there were contraindications for ibuprofen. The patients were divided into two groups: patients receiving IV ibuprofen and patients receiving IV paracetamol. Results Of these patients, 101 were given IV paracetamol and 169 were given IV ibuprofen. The success rate of PDA closure with first-course treatment was 74.3% in the IV paracetamol group and 72.8% in the IV ibuprofen group (p=0.212). Conclusions Our results show that IV paracetamol is as effective as IV ibuprofen in the first-line treatment of hsPDA, and can become the preferred treatment for the management of hsPDA.

Perfil epidemiológico de pacientes intoxicados con acetaminofén con intenciones suicidas / Epidemiological profile of patients intoxicated with acetaminophen for suicidal purposes / Perfil epidemiológico de pacientes intoxicados com acetaminofen (Paracetamol) com intenções suicidas

Objetivo: este estudio busca describir los individuos evaluados por sobredosis de acetaminofén entre 2019 y 2020 en un centro de referencia de trasplante hepático en Colombia. Metodología: estudio derivado del análisis secundario de historias clínicas entre el 1.º de enero de 2019 y el 31 de diciembre de 2020. Los criterios de inclusión abarcan individuos con ingestión aguda y voluntaria de dosis tóxicas de acetaminofén (>4 g/día). Resultados: sesenta y tres casos, 68% mujeres, 67% menores de 18 años y 54% estudiantes. Reportó historia personal de enfermedad psiquiátrica el 60% y el 35% al menos un intento de suicidio previo. La mediana de dosis de acetaminofén fue 15g, 46% refirieron co-ingesta de otras sustancias y 13% estaba bajo efecto de sustancias psicoactivas. El 57% tenía la intención clara de suicidarse, así como 81% vomitó antes de acudir al servicio de urgencias, 22% recibió medidas de descontaminación y 10% no recibió N - acetilcisteína. Quince individuos desarrollaron lesión hepática aguda, nueve con criterios de severidad. Conclusiones: la población era predominantemente joven, la historia de enfermedad psiquiátrica fue muy prevalente y la mayoría refirieron un evento vital que explicara el comportamiento impulsivo de consumo. Ninguno desarrolló criterios para trasplante hepático, lo cual podría explicarse por la edad de los individuos, los episodios de vómito temprano, y la ausencia de enfermedad hepática crónica o de consumo de sustancias hepatotóxicas.

Objective: this study aims to describe patients with overdose intake of acetaminophen between 2019 and 2020 at a reference center for liver transplantation in Colombia. Methodology: study derived from a secondary analysis of the clinical records between January 1st, 2019, to December 31st, 2020. Inclusion criteria were individuals with voluntary acute ingestion of toxic doses of acetaminophen (>4 g/day). Results: sixty-three cases, 68% women, 67% <18-year-old, and 54% students. 60% had personal history of psychiatric illness and 35% reported at least one previous suicide attempt. The median dose of acetaminophen was 15g, 46% referred to co-ingestion with other substances and 13% were under the effect of any psychoactive substance. 57% had a clear intention of suicide. 81% vomited before the arrival to the emergency room, 22% received decontamination intervention with gastric lavage or activated charcoal, and 10% did not receive any dose of N-Acetylcysteine. Fifteen individuals developed an acute liver injury, nine with severity criteria. Conclusions: the population was predominantly young, the personal history of psychiatric disease was highly prevalent, and most of the cases referred a vital event that explains the impulsive behavior in acetaminophen consumption. None developed criteria for liver transplantation, and this could be explained by the young age of the individuals, the episodes of early vomiting, and the absence of chronic liver disease or hepatotoxic substance consumption.

Objetivo:este estudo busca descrever os indivíduos avaliados por sobredose de acetaminofen entre 2019 e 2020 num centro de referência de transplante hepático na Colômbia. Metodologia: estudo derivado da análise secundário de histórias clínicas entre o dia 1.º de janeiro de 2019 e 31 de dezembro de 2020. Os critérios de inclusão abrangem indivíduos com ingestão aguda e voluntária de dose tóxicas de acetaminofen (>4 g/dia).Resultados:sessenta e três casos, 68% mulheres, 67% menores de 18 anos e 54% estudantes. Reportou história pessoal de doença psiquiátrica, 60% e 35% pelo menos uma tentativa de suicídio prévio. A média de dose de acetaminofen foi de 15g, 46% referiram com ingestão de outras sustâncias e 13% estava sob efeito de sustâncias psicoativas. 57% tinham a intenção clara de suicidar-se, assim como 81% vomitou antes de acudir ao serviço de urgências, 22% receberam medidas de descontaminação e 10% não recebeu N - acetilcisteína. Quinze indivíduos desenvolveram lesão hepática aguda, nove com critérios de severidade. Conclusões: a população era predominantemente jovem, a história de doençapsiquiátrica foi muito prevalente e a maioria referiram um evento vital que explicasse o comportamento impulsivo de consumo. Nenhum desenvolveu critérios para transplantehepático, o qual se poderia explicar pela idade dos indivíduos, os episódios de vómito precoce, e a ausência de doença hepática crónica ou de consumo de sustâncias hepatotóxicas.

Pentazocine versus tramadol-paracetamol combination as analgesia in labor: A randomized controlled trial

Objectives: Labor should be a satisfactory experience and effective pain management should be employed as recommended by the American Congress of Obstetricians and Gynaecologists. In developing countries, pain management in labor is still a big challenge and the search for the ultimate labor analgesia is still ongoing. The objectives of the study were to determine whether the synergistic analgesic effect of the combination of tramadol and paracetamol will produce analgesia comparable to pentazocine with a better side effect profile. Material and Methods: This was a randomized controlled, double-blinded trial of tramadol-paracetamol combination versus pentazocine as labor analgesia and was carried out at the University of Abuja Teaching Hospital, Abuja, between June 2018 and March 2019. A total of 218 eligible parturients recruited at term, were counseled on labor analgesia, its benefits, and the options made available to them and educated on the pain scoring system. Parturients were allocated into two groups using computer-generated numbers with the WINPEPI software. Group A was given tramadol-paracetamol combination, while Group B received pentazocine, both at standard doses. Hourly pain scores, APGAR scores, labor duration, patients' satisfaction, and side effects were collated. The level of significance was set at <0.05. Results: Tramadol-paracetamol was administered to 109 (50.9%) while pentazocine was administered to105 (49.1%) of the study participants. The mean age in the tramadol-paracetamol group was 29.6 ± 4.8 years, and in the pentazocine group, it was 28.8 ± 4.5 years. The difference in pain scores on the visual analog scale was statistically significant at the 3rd and 4th h (P = 0.02 and 0.004), but not significant in the 1st and 2nd h (P = 0.05 and 0.22) in the two groups. Overall, the average pain score in the tramadol-paracetamol group was significantly higher compared to the pentazocine group (5.27 ± 1.86 vs. 4.72 ± 1.54; P = 0.02). The 1st and 5th min APGAR scores (P = 0.44 and 0.67, respectively) of neonates in the tramadol-paracetamol and pentazocine groups were comparable. Nausea and drowsiness occurred more frequently in the pentazocine group at P-values of 0.047 and 0.0015, respectively. There was no statistically significant difference in the duration of labor between the tramadol-paracetamol and pentazocine groups. not statistically significant, a higher proportion of parturients in the pentazocine group was satisfied compared with the tramadol-paracetamol group (71.4% vs. 63.3%; P = 0.13).Conclusion: This study showed that intravenous pentazocine provides better pain relief in labor, but the tramadol-paracetamol combination has fewer side effects

Molecular pathogenesis of acetaminophen-induced liver injury and its treatment options / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Acetaminophen, also known as N-acetyl-p-aminophenol (APAP), is commonly used as an antipyretic and analgesic agent. APAP overdose can induce hepatic toxicity, known as acetaminophen-induced liver injury (AILI). However, therapeutic doses of APAP can also induce AILI in patients with excessive alcohol intake or who are fasting. Hence, there is a need to understand the potential pathological mechanisms underlying AILI. In this review, we summarize three main mechanisms involved in the pathogenesis of AILI: hepatocyte necrosis, sterile inflammation, and hepatocyte regeneration. The relevant factors are elucidated and discussed. For instance, N-acetyl-p-benzoquinone imine (NAPQI) protein adducts trigger mitochondrial oxidative/nitrosative stress during hepatocyte necrosis, danger-associated molecular patterns (DAMPs) are released to elicit sterile inflammation, and certain growth factors contribute to liver regeneration. Finally, we describe the current potential treatment options for AILI patients and promising novel strategies available to researchers and pharmacists. This review provides a clearer understanding of AILI-related mechanisms to guide drug screening and selection for the clinical treatment of AILI patients in the future.

Induction of peripheral blood mononuclear cells to hepatocyte-like cells and preliminary study of cell response to injury under the effect of acetaminophen / 中华肝脏病杂志

Objective: To establish a method for the induction of peripheral blood mononuclear cells to hepatocyte-like cells, and preliminarily investigate cell response to injury under the effect of acetaminophen (APAP). Methods: The surface marker CD45 of peripheral blood mononuclear cells wase detected cells by using flow cytometry and immunofluorescence methods. The cellular morphology of induced hepatocyte-like cells was observed under an inverted microscope. Real-time fluorescent quantitative PCR (RT-PCR) was used to detect the expression level of hepatocyte-specific genes, such as cytochrome (CY) P1A2, CYP3A4, CYP2C9, albumin (ALB), alpha-fetoprotein (AFP), and hepatocyte nuclear factor (HNF)4α mRNA. Immunofluorescence method was used to detect intracellular hepatocyte markers AFP, HNF4α, and ALB expression at the protein level. Biochemical analyzer was used to detect hepatocyte-specific secretory functions of AFP, ALB, and urea. Luciferase chemiluminescence method was used to detect the activity of key drug metabolizing enzyme CYP3A4. Colorimetric assay was used to detect the effect of the drug acetaminophen on hepatocyte-like cells, and alanine aminotransferase (ALT) was used as an indicator of liver cell injury. The statistical differences between the data were compared with t-test and rank-sum test. Results: The positive expression rate of CD45 cell surface markers isolated from peripheral blood mononuclear cells was about 98%, and hepatocyte-like cell morphology changes appeared on 15th day of induction. Compared with isolated mononuclear cells, CYP1A2, CYP3A4, CYP2C9, ALB, AFP and HNF4α mRNA was markedly elevated. The expression level of AFP, ALB and HNF4α protein were equally increased, and the secretory function of AFP, ALB and urea were enhanced. Compared with primary hepatocytes, CYP1A2, CYP2C9, AFP, HNF4α mRNA, and CYP3A4 mRNA did not decrease. The expression levels of AFP, ALB, and HNF4α proteins in the cells did not decrease, and the secretory function of AFP, ALB, and urea did not decrease. In addition, the CYP3A4 enzyme activity produced by hepatocyte-like cells was similar to that of primary hepatocytes. Compared with hepatocyte-like cells incubated without APAP, hepatocyte-like cells incubated with APAP had higher ALT level. Under the effect of APAP, the ALT level of hepatocyte-like cells was higher than isolated mononuclear cells. Conclusion: Peripheral blood mononuclear cells can be induced into hepatocyte-like cells with partial characteristics of hepatocytes, including the activity of CYP3A4, a key enzyme of hepatocyte drug metabolism. Additionally, preliminarily ALT secretory features reflect the hepatocytes injury under the effect of acetaminophen.

Mechanism of Tibetan medicine Ershiwuwei Songshi Pills against liver injury induced by acetaminophen in mice based on Keap1/Nrf2 and TLR4/NF-κB p65 signaling pathways / 中国中药杂志

The present study investigated the mechanism of the Tibetan medicine Ershiwuwei Songshi Pills(ESP) against the liver injury induced by acetaminophen(APAP) in mice based on the kelch-like ECH-associated protein 1(Keap1)/nuclear transcription factor E2 related factor 2(Nrf2) and Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) p65 signaling pathways. Kunming mice were randomly divided into a blank control group, a model group, an N-acetyl-L-cysteine(NAC) group, and high-(400 mg·kg~(-1)), medium-(200 mg·kg~(-1)), and low-dose(100 mg·kg~(-1)) ESP groups. After 14 days of continuous administration, except for those in the control group, the mice were intraperitoneally injected with 200 mg·kg~(-1) APAP. After 12 h, the serum and liver tissues of mice were collected. Hematoxylin-eosin(HE) staining was performed on pathological sections of the liver, and the levels of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the serum and the levels of glutathione(GSH), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), myeloperoxidase(MPO), and total antioxidant capacity(T-AOC) in liver tissue homogenate were detected to observe and analyze the protective effect of ESP on APAP-induced liver injury in mice. The serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), and interleukin-6(IL-6) were determined by enzyme-linked immunosorbent assay(ELISA). The protein expression of Nrf2, Keap1, TLR4, and NF-κB p65 in the liver was determined by Western blot. Quantitative real-time was used to determine the mRNA expression of glutamate-cysteine ligase catalytic subunit(GCLC), glutamate-cysteine ligase regulatory subunit(GCLM), heme oxygenase-1(HO-1), and NAD(P)H dehydrogenase quinone 1(NQO-1) in the liver to explore the mechanism of ESP in improving APAP-induced liver damage in mice. As revealed by results, compared with the model group, the ESP groups showed improved liver pathological damage, decreased ALT and AST levels in the serum and MDA and MPO content in the liver, increased GSH, SOD, CAT, and T-AOC in the liver, reduced TNF-α and IL-6 levels in the serum, down-regulated expression of Keap1 in the liver cytoplasm and NF-κB p65 in the liver nucleus, up-regulated expression of Nrf2 in the liver nucleus, insignificant change in TLR4 expression, and elevated relative mRNA expression levels of antioxidant genes GCLC, GCLM, HO-1, and NQO-1. ESP can reduce the oxidative damage and inflammation caused by APAP, and the mechanism may be related to the Keap1/Nrf2 signaling pathway and the signal transduction factors on the TLR4/NF-κB p65 pathway.