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RESUMEN Introducción: La cardiopatía isquémica es la principal causa de muerte en la República Argentina. La forma de presentación que prevalece es el infarto de miocardio (IM), caracterizado por insuficiente perfusión sanguínea, muerte celular y pérdida de masa contráctil. La evolución del remodelado ventricular provoca dilatación ventricular, deterioro hemodinámico, insuficiencia cardíaca y disminución de la sobrevida. Durante este proceso existe un estrés oxidativo miocárdico que podría ser atenuado mediante la administración de N-acetil cisteína (NAC), a través de un aumento de los niveles de glutatión. Objetivos: Evaluar el efecto de la NAC sobre el remodelado post IM. Material y métodos: Se estudiaron durante 28 días conejos neozelandeses en tres grupos experimentales: Control, IM e IM+NAC. Bajo anestesia general se realizó una toracotomía izquierda y, en los grupos con IM, ligadura de una rama de la coronaria izquierda. Al finalizar el período de seguimiento posterior al infarto, se realizaron estudios ecocardiográficos, hemodinámicos y morfológicos del ventrículo izquierdo (VI). Resultados: En los grupos IM e IM+NAC los infartos estaban ubicados en la pared libre del VI y tuvieron tamaños similares. La administración de NAC evitó el adelgazamiento de la zona no infartada y disminuyó la dilatación provocada por el infarto. También pudo observarse que preservó las funciones sistólica y diastólica del VI, con atenuación del deterioro que las mismas sufrieron como consecuencia del infarto. Conclusión: Estos resultados sugieren que la administración de NAC es una terapéutica promisoria para mitigar los efectos desfavorables del remodelado post IM.
ABSTRACT Background: Ischemic heart disease is the main cause of death in Argentina. The prevailing form of presentation is myocardial infarction (MI), characterized by insufficient blood perfusion, cell death and loss of contractile mass. The evolution of ventricular remodeling causes ventricular dilation, hemodynamic impairment, heart failure, and decreased survival. The oxidative stress occurring during this process could be attenuated by the administration of N-acetyl cysteine (NAC) through increased glutathione levels. Objectives: The aim of this study was to evaluate the effect of NAC administration on post-MI remodeling. Methods: New Zealand rabbits were divided into three experimental groups: Control, MI and MI+NAC. A left thoracotomy was performed under general anesthesia, and in the MI groups a branch of the left coronary artery was ligated. Echocardiographic, hemodynamic and morphological studies of the left ventricle were performed at the end of the 28-day post infarction follow-up period. Results: In the MI and MI+NAC groups, the infarcts were located in the left ventricular free wall and had similar sizes. The administration of NAC prevented non-infarcted area thinning and decreased the dilation caused by the infarction. It also preserved left ventricular systolic and diastolic functions, attenuating the impairment that they suffered as a consequence of the infarction. Conclusion: These results suggest that NAC administration is a promising therapy to mitigate the unfavorable effects of post-MI remodeling.
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Introducción: la hipersensibilidad por fármacos es inducida por una respuesta aberrante del sistema inmune; por lo general, impredecible, dosis independiente y amenazante para la vida del paciente. Las reacciones de hipersensibilidad por fármacos con compromiso mucocutáneo se dan en alrededor del 2 %-3 % de los pacientes hospitalizados. Objetivo: describir un caso de necrólisis tóxica epidérmica por un fármaco a base de caléndula y acetilcisteína como los presuntos desencadenantes. Presentación del caso: hombre de 39 años, quien asistió a emergencias, por malestar general, artralgias, mialgias, astenia y adinamia de un día de evolución. Tres días después refirió la aparición de lesiones purpúricas progre-sivas que se extendieron por cara, extremidades y glúteos; delimitadas; no dolorosas, y sin desaparecer a la digitopresión, asociado con disnea, inestabilidad hemodinámica y cardiovascular. Al sexto día de hos-pitalización, se interrogó al paciente, quien se había automedicado un fármaco de origen desconocido, presuntamente de extracto herbal a base de caléndula más acetilcisteína para artralgias, osteomialgias y disfagia. A la mañana siguiente, presentó lesiones purpúricas y ulcerativas extensas. Se observaron lesiones purpúricas progresivas y ulcerativas en cara extremidades y glúteos. Mediante la sospecha clínica y la evaluación histopatológica, se confirmó la necrólisis tóxica epidérmica. Conclusiones: las reacciones adversas medicamentosas severas que amenazan la vida del paciente son relativamente raras, pero representan un verdadero desafío diagnóstico y terapéutico. Es necesario profundizar en la investigación para esclarecer la causa de este tipo de reacción medicamentosa.
Introduction: Drug hypersensitivity is induced by an aberrant response from the immune system. It is usually unpredictable, dose-independent, and can be life-threatening to the patient. Drug-induced hypersensitivity reactions with mucocutaneous involvement occur in approximately 23% of hospitalized patients. However, Toxic Epidermal Necrolysis is a rare case. Aim: To describe a case of drug-induced toxic epidermal necrolysis triggered by Calendula officinalis and acetylcysteine. Case report: A 39-year-old male was pre-sented to the emergency room with malaise, arthralgia, myalgia, asthenia, and adynamia since day one. Three days later, he developed progressive purpuric lesions that spread to the face, extremities, and buttocks. These lesions were painless, not delineate, and did not blanch under pressure. They were asso-ciated with dyspnea and hemodynamic and cardiovascular instability. On the sixth day of hospitaliza-tion, the patient admitted to self-medicating with an unknown drug, presumably a herbal extract based on calendula and acetylcysteine, for arthralgia, myalgia, and dysphagia. The morning after the drug consumption, the patient developed extensive purpuric and ulcerative lesions. A diagnosis of toxic epi-dermal necrolysis was made based on clinical suspicion and histopathological confirmation. Conclusion:Severe adverse drug reactions that threaten a patient's life are relatively rare. However, they represent a real diagnostic and therapeutic challenge when they do occur
Introdução: a hipersensibilidade a drogas é induzida por uma resposta aberrante do sistema imunoló-gico; geralmente imprevisível, independente da dose e com risco de vida para o paciente. As reações de hipersensibilidade a drogas com comprometimento mucocutâneo estão em torno dos 2-3% dos pacien-tes hospitalizados. Objetivo: descrever um caso de necrólise epidérmica tóxica causada por uma droga à base de Calendula officinalis e acetilcisteína como os supostos desencadeantes. Apresentação do caso:homem, 39 anos, deu entrada no pronto-socorro manifestando mal-estar, artralgia, mialgia, astenia e adinamia há um dia. Posteriormente, três dias depois, relatou o aparecimento de lesões purpúricas pro-gressivas que se espalharam para a face, extremidades e nádegas; que são delimitadas, não dolorosas e não desaparecem com a acupressão associada a dispnéia, instabilidade hemodinâmica e cardiovascular. No sexto dia de internação, o paciente foi questionado, y disse que tinha se automedicado com uma droga de origem desconhecida, presumivelmente extrato de ervas à base de calêndula mais acetilcis-teína para artralgia, osteomialgia e disfagia. Na manhã seguinte, apresentou extensas lesões purpúricas e ulcerativas. Observam-se lesões purpúricas progressivas e ulcerativas que se estendem à face, extre-midades e nádegas. Pela suspeita clínica e confirmação histopatológica, confirma-se a necrólise epidér-mica tóxica. Conclusões: reações adversas graves a medicamentos que ameaçam a vida do paciente são relativamente raras, mas quando ocorrem representam um verdadeiro desafio a nível diagnóstico e terapêutico. São precisas mais pesquisas para esclarecer a causa desse tipo de reação medicamentosa.
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HumanosRESUMO
Ischemic stroke (CIS) refers to ischemic necrosis or softening of localized brain tissue caused by cerebral blood circulation disorders, ischemia and hypoxia. The incidence of CIS is the highest among cerebrovascular diseases. Reduced supply of oxygen and nutrients leads to severe loss of neurons and deficits in brain function in stroke patients. Developing treatments for ischemic stroke remains an important challenge in clinical medicine. The antioxidant N-acetylcysteine (NAC) is a precursor of glutathione, and evidence from animal models of ischemic stroke and some clinical studies suggest that NAC can effectively protect the brain from ischemic damage. In this paper, the mechanism of NAC in CIS is described from various aspects, such as anti-oxidation, inhibition of inflammation, protection of cerebral nerve and mitochondrial function, stabilization of arterial plaque and thrombolytic function, aiming to explore the relationship between NAC and CIS in depth from the basic level, and to provide a theoretical basis for the further application of NAC in the prevention and treatment of patients with ischemic stroke.
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Abstract Objective: This study investigated the effects of N-Acetylcysteine (NAC) combined with Ambroxol Hydrochloride (AH) on clinical symptoms, C-Reactive Protein (CRP), and Procalcitonin (PCT) levels in children with pneumonia. Methods: A total of 98 children with pneumonia were assigned to the control group and observation group by random number table method. NAC was administered to the observation group and AH was given to the control group. The therapeutic effect was observed, the disappearance time of clinical symptoms and levels of inflammatory factors, lung function parameters, blood gas analysis parameters, and immunoglobulin were measured. The incidence of adverse reactions was statistically analyzed. Results: A higher effective rate was observed in the observation group than in the control group (p < 0.05). Antipyretic time, cough disappearance time, and lung rale disappearance time in the observation group were shorter than those in the control group (p < 0.05). After treatment, CRP and PCT were lower (p < 0.05), FVC, FEV1, and FEV1/FVC were higher, PaCO2 was lower, PaO2 and SaO2 were higher, and IgA, IgG, IgM, and C3 were higher in the observation group than those in the control group (p < 0.05). The incidence of adverse reactions between the two groups was not significantly different (p > 0.05). Conclusion: NAC combined with AH is effective in the treatment of pediatric pneumonia by effectively alleviating clinical symptoms, reducing inflammatory factors, and improving lung function and immune function.
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RESUMEN El objetivo de esta revisión sistemática fue estimar la efectividad de la N-acetilcisteína en el tratamiento de hepatotoxicidad por antituberculosos; se incluyeron ensayos clínicos controlados aleatorizados, sin restricciones de idioma ni estado de publicación; se tuvieron en cuenta estudios publicados hasta diciembre de 2022. Búsqueda en bases de datos bibliográficas: CENTRAL, CINAHL, LILACS, MEDLINE, Pubmed, Scielo, Scopus y Web of Science; de 33 artículos encontrados, uno cumplió los criterios de inclusión con bajo riesgo de sesgos. El tiempo a mejoría bioquímica del grupo intervención fue 7,5 días (RIQ 5,5-11) y en el grupo placebo 8 (RIQ 5-13). El tiempo de estancia hospitalaria en el grupo intervención fue 9 días (RIQ 6-15) y en el grupo placebo 18 (RIQ 10-25). La mortalidad no difirió entre grupos y fue 14 %. No es posible concluir sobre el efecto terapéutico de la N-acetilcisteína en pacientes con DILI por antituberculosos, lo cual justifica realizar ensayos clínicos.
ABSTRACT The aim of this systematic review was to estimate the effectiveness of N-Acetylcysteine in the treatment of hepatotoxicity induced by antitubercular agents, we included randomized clinical trials, there was no language nor publication status restriction, published until December 2021. The searched databases were CENTRAL, CINAHL, LILACS, MEDLINE, Pubmed, Scielo, Scopus y Web of Science; out of 33 articles found, one of them met the inclusion criteria and had low bias risk. The time to biochemical resolution was 7,5 days (IQR 5,511) in the treatment arm, and 8 (IQR 5-13) in the placebo arm. Time of hospital stay was 9 days (IQR 6-15) in the treatment arm, and 18 (IQR 10-25) in the placebo arm. Mortality (14 %) didn't differ between groups. Further clinical trials may be needed to determine the therapeutic role of N-acetylcysteine in patients with drug-induced liver injury caused by antituberculous agents.
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Acetaminophen is a drug widely used in the world and easily accessible due to its antipyretic, analgesics characteristics, among others (1); however, exposure to toxic doses causes organic damage and even death. We present the case of an 18-year-old female patient who ingested 40 grams of acetaminophen and developed severe liver dysfunction, being treated with N-acetylcysteine (NAC) antidotal therapy according to the simplified scheme: Scottish and Newcastle Anti-emetic Pretreatment Paracetamol Poisoning Study Regimen (SNAP), presenting improvement in the clinical course and decrease in liver profiles, coagulation disorder, INR and resolution of the condition.
El acetaminofén es un fármaco ampliamente usado en el mundo y de fácil acceso por sus características antipiréticas, analgésicas, entre otras (1); sin embargo la exposición a dosis tóxicas produce daños a nivel orgánico e incluso la muerte. Presentamos el caso de una paciente mujer de 18 años que ingirió 40 gramos de acetaminofén y desarrolló injuria hepática severa, siendo tratada con terapia antidotal de N-acetilcisteína (NAC) según el esquema simplificado: Scottish and Newcastle Anti-Emetic Pretreatment Paracetamol Poisoning Study Regimen (SNAP), presentando mejoría del curso clínico y disminución de los perfiles hepáticos, trastorno de coagulación, INR y resolución del cuadro.
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Objective:To investigate the efficacy of atomization with budesonide, salbutamol, and acetylcysteine in the adjuvant treatment of bronchopneumonia in children.Methods:Seventy-two children with bronchopneumonia admitted to Huaiyuan Jingtu Hospital from July 2021 to June 2022 were retrospectively included in this study. These children were divided into BS and BSY groups according to different treatment methods. Based on conventional treatment, the BS group was given atomization treatment with budesonide and salbutamol, and the BSY group was given atomization treatment with budesonide, salbutamol, and acetylcysteine. After two courses of treatment, clinical efficacy, duration to improvements in symptoms and signs, adverse drug reactions, and changes in serum C-reactive protein and procalcitonin levels after treatment relative to those before treatment were compared between the two groups. The optimal medication plan was investigated.Results:The total response rate in the BSY group was 91.67% (33 cases/36 cases), which was significantly higher than 72.22% (26/36) in the BS group ( χ2 = 4.59, P = 0.032). The incidence of adverse drug reactions in the BSY group was 11.11% (4/36), which was significantly lower than 19.44% (7/36) in the BS group ( χ2 = 0.96, P = 0.326). After treatment, the levels of C-reactive protein and procalcitonin in the BSY group were (5.86 ± 5.66) mg/L and (2.59 ± 0.74) μg/L, respectively, which were lower than (15.64 ± 5.85) mg/L and (4.71 ± 0.93) μg/L in the BS group ( t = 7.20, 10.70, both P < 0.001). The durations to the disappearance of symptoms and signs including fever, cough, lung rales, and X-ray lung shadow in the BSY group were significantly shorter compared with the BS group ( t = 11.85, 4.19, 2.72, 2.39, all P < 0.05). Conclusion:Atomization with budesonide, salbutamol, and acetylcysteine in combination for the adjuvant treatment of bronchopneumonia in children can quickly relieve the clinical symptoms of children, improve the lung signs, reduce the degree of inflammation, and has a remarkable therapeutic effect on bronchopneumonia in children.
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OBJECTIVE To assess whether N-acetylcysteine(NAC)and reduced glutathione(GSH)are effective in reversing flupirtine-induced hepatotoxicity and whether they have other bene-ficial effects when combined with flupirtine.METHODS The analgesic effects of NAC and flupirtine were first evaluated in carrageenan-induced inflammatory pain and paclitaxel-induced neuropathic pain.The combination subthreshold-ing approach was then used to determine whether the combination of NAC and flupirtine produced synergistic analgesic effects.Hepatotoxicity markers and histopathological examination of the liver were used to assess the efficacy of NAC and GSH in reversing flupirtine-induced hepato-toxicity.Finally,the effect of GSH on the safe range of flupirtine was assessed in an acute tox-icity assay.RESULTS Flupirtine and NAC pro-duced dose-dependent antiallodynic effects evoked by carrageenan and paclitaxel in mice.In the above model,the combination of NAC and flupirtine produced an unexpected synergistic analgesic effect.There were no significant differ-ences observed in the hepatotoxicity markers and liver histopathology between the experimen-tal group and the control group under NAC and GSH treatment.Finally,GSH(200 mg·kg-1)expanded the therapeutic index of flupirtine by 1.77 times.CONCLUSION NAC and GSH are effective in preventing liver damage caused by long-term flupirtine use,which provides a solu-tion for the safe and effective treatment of chronic pain with flupirtine.In addition,the other benefi-cial effects of NAC and GSH when combined with flupirtine may provide the basis for the devel-opment of a new therapy with minimal side-effects and good efficacy.
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Objective@#To retrospectively analyze the efficacy of aerosol inhalation of N-acetylcysteine(NAC) solution combined with bronchoalveolar lavage in children with Mycoplasma pneumoniae pneumonia(MPP) .@*Methods@#A retrospective study was conducted on 120 children with MPP. According to different treatment methods ,they were divided into combined treatment group (43 cases) ,atomization group (40 cases) and bronchoalveolar lavage group (37 cases) .Among them,while receiving conventional treatment,children who were treated with aerosol inhalation of N-acetylcysteine alone were included in the atomization group,and those who were treated with bronchoalveolar lavage alone were included in the bronchoalveolar lavage group,and children treated with the combination of the above two treatments were included in the combined treatment group.The clinical efficacy,imaging recovery and incidence of adverse reactions were compared among all groups. @*Results@#Compared the total effective rate among the three groups,there was no significant difference between the atomization group and the bronchoalveolar lavage group (P>0. 05) ,which were both lower than that of the combined treatment group (P<0. 05) ; the difference in the improvement rate of lung imaging among the three groups was statistically significant (P<0. 05) , the combined treatment group was the highest,and the BAL group was higher than the atomization group ; There was no significant difference in the duration of fever and pulmonary rales between the combined treatment group and the BAL group (P>0. 05) ,which were shorter than those in the atomization group (P<0. 05) ; There was no significant difference in duration of cough,shortness of breath and hospital stay between the atomization group and the BAL group (P>0. 05) ,which were longer than those in the combined treatment group (P>0. 05) .There was no serious adverse reactions in the three groups.There was no significant difference in the three groups(P>0. 05) . @*Conclusion@#Compared with single treatment ,N-acetylcysteine solution combined with bronchoalveolar lavage is more effective and has more advantages in the treatment of Mycoplasma pneumoniae pneumonia in children.
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Objective:To observe the effect of the antioxidant N-acetylcysteine (NAC) and selective endoplasmic reticulum stress response inhibitor salubrinal on the apoptosis of retinal pigment epithelial cells induced by all-trans-retinoic acid (ATRA).Methods:Human ARPE-19 cell line was used as the experimental cell line, and was divided into normal control group cultured with complete medium, model control group cultured with complete medium containing 10 μmol/L ATRA, NAC treatment group cultured with complete medium containing 10 μmol/L ATRA+ 5 mmol/L NAC, salubrinal group cultured with complete medium containing 10 μmol/L ATRA+ 40 μmol/L salubrinal, NAC+ salubrinal group cultured with complete medium containing 10 μmol/L ATRA+ 5 mmol/L NAC+ 40 μmol/L salubrinal.After 24-hour culture, apoptosis rate, multicaspase level and reactive oxygen species (ROS) level of ARPE-19 cells were detected by flow cytometry.The expressions of vascular endothelial growth factor A (VEGF-A), C/EBP-homologous protein (CHOP), cleaved-caspase 3 in cells were detected by Western blot.Results:There were significant differences in the apoptosis rate, multicaspase and ROS levels among the five groups ( F=113.23, 602.41, 160.39; all at P<0.001). The apoptosis rate, multicaspase and ROS levels of normal control group, NAC treatment group, salubrinal group and NAC+ salubrinal group were significantly lower than those of model control group (all at P<0.05). There were significant differences in the expression levels of VEGF-A, CHOP and cleaved-caspase 3 among the five groups ( F=24.62, 36.35, 60.25; all at P<0.001). The protein expression levels of VEGF-A, CHOP and cleaved-caspase 3 of normal control group, NAC treatment group, salubrinal group and NAC+ salubrinal group were significantly lower than those of model control group (all at P<0.05). Conclusions:ATRA can induce RPE cells to produce oxidative stress and endoplasmic reticulum stress injury, which leads to apoptosis.NAC and salubrinal can effectively reduce the RPE cell apoptosis by inhibiting stress response.
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Purpose: To evaluate the tissue content of neutral and acidic mucins, sulfomucins and sialomucins in colonic glands devoid of intestinal transit after enemas containing sucralfate and n-acetylcysteine alone or in combination. Methods: Sixty-four rats underwent intestinal transit bypass. A colonic segment was collected to compose the white group (without intervention). After derivation, the animals were divided into two groups according to whether enemas were performed daily for two or four weeks. Each group was subdivided into four subgroups according to the substance used: control group: saline 0.9%; sucralfate group (SCF): SCF 2 g/kg/day; n-acetylcysteine group (NAC): NAC 100 mg/kg/day; and SCF+NAC group: SCF 2 g/kg/day + NAC 100 mg/kg/day.Neutral and acidic mucins were stained by periodic acid-Schiff and alcian-blue techniques, respectively. The distinction between sulfomucins and sialomucin was made by the high alcian-blue iron diamine technique. The content of mucins in the colonic glands was measured by computerized morphometry. The inflammatory score was assessed using a validated scale. The results between the groups were compared by the Mann-Whitney's test, while the variation according to time by the Kruskal-Wallis' test (Dunn's post-test). A significance level of 5% was adopted. Results: There was reduction in the inflammatory score regardless of the application of isolated or associated substances. Intervention with SCF+NAC increased the content of all mucin subtypes regardless of intervention time. Conclusions: The application of SCF+NAC reduced the inflammatory process of the colonic mucosa and increased the content of different types of mucins in the colonic glands of segments excluded from fecal transit.
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Animais , Ratos , Acetilcisteína , Sucralfato , Colite , MucinasRESUMO
Background: Patients with chronic kidney disease (CKD) are at a common risk for contrast-induced acute kidney damage (CI-AKI) because of various complications. Intravenous N-acetylcysteine (NAC) in high doses (1200mg) is considered more effective than its conventional dose (600mg) to prevent CIN and related complications. Objective: The study aimed to compare the effectiveness of high dose versus standard dose of intravenous N-acetylcysteine (NAC) in the prevention of Acute Kidney Injury in patients with chronic kidney disease.Material & Methods:A total of 60 (sixty) patients diagnosed with CKD went to coronary angiography and/or percutaneous coronary intervention (PCI) were selected by simple random technique and categorized into two groups – Group A (30 patients) received high dose NAC (1200mg) and Group B (30 patients) – received standard dose NAC (600mg). For evaluation of renal damage serum creatinine level for at least >3 months, renal imaging revealed bilateral small echogenic kidneys, eGFR (<60 to 15ml/min/1.73m², measured by MDRD formula) and also by ACR >30 mg/gm, associated with IHD, admitted for percutaneous intervention (PCI) were taken in account. Statistical analysis was done by SPSS version 20 with taking 95% confidence interval. The quantitative data were expressed as mean and standard deviation and qualitative data were expressed as frequency distribution and unpaired t-test, Chi-square test, and Fisher exact analytic test were done.Results:The observed mean age group of the patients was 65 ± 8 years and 62 ± 7 years in group A and group B respectively with male predominance in both groups. Primary renal disease diabetic nephropathy (DN) more (36.66%) in group A than in group B (30.00%) but patients with Hypertensive nephropathy were the same (33.33%) in both groups. After interventions, S. Creatinine (mg/dl) level, e, GFR (ml/min/1.73m²), were statistically significant in cases of group A patients (P-value 0.001& 0.003 correspondingly) compared to group B Patients (P-value 0.075 & 0.001 respectively). Again, the mean of pre-intervention S. Creatinine was 1.7 ±0.5 in group A whereas this was 1.9 ± 0.8 (p-value, 0.599) in group B and after 48 hours of intervention this was 1.6 ± 0.5 and 2.0 ± 0.5 (p-value, 0.697) In group A and group B respectively. Overall, no patients were detected with nephropathy for high dose NAC whereas 27 (90%) out of 30 had developed CIN in standered dose.Conclusion:High-dose N-acetylcysteine (1200mg) is more potent and effective than the standard dose (600mg) in reducing contrast-induced acute kidney injury (CI-AKI) in patients with CKD.
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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.
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Humanos , Acetaminofen , Acetilcisteína , Tentativa de Suicídio , Vômito Precoce , Carvão Vegetal , Descontaminação , Serviço Hospitalar de Emergência , Dosagem , Lavagem Gástrica , Hepatopatias , Transtornos MentaisRESUMO
Objective:To investigate the effect of N-acetylcysteine (NAC) on endoplasmic reticulum stress (ERS) and oxidative stress(OS) induced by tunicamycin (Tm) and its mechanism.Methods:Mouse derived brain microvascular endothelial cells cultured in vitro were divided into control group (normal cell culture), TM group (cells were intervened with 5 μg/mL Tm for 24 h), NAC + TM group (cells were pretreated with 1 mmol/L NAC for 1 h, then were intervened with 5 μg/mL Tm for 24 h) and NAC group (cells were intervened with 1 mmol/L NAC for 24 h) according to different intervention methods.CCK-8 and FITC-Annexin V/PI were used to detect the survival rate and apoptosis rate of cells.Western blot was used to detect the expression of GRP78、CHOP、p-eNOS and caspase-12 protein. Laser confocal microcopy was used to detect the expression of ROS, and colorimetry was used to detect the activity of MDA and SOD.Results:There were significant differences in apoptosis rate and survival rate among the four groups ( F=62.57, 35.00, both P<0.05). The apoptosis rate of TM group ((25.49±1.55)%) was higher than that of Control group ((13.76±1.48)%)( P<0.01), while the apoptosis rate of NAC+ TM group ((17.65±1.00)%) was lower than that of TM group ( P<0.01). The survival rate of TM group ((66.33±5.69)%) was lower than that of Control group ((100.00±2.12)%)( P<0.01), while the survival rate of NAC+ TM group ((85.67±4.04)%) was higher than that of TM group ( P<0.01). Western blot showed that there were significant differences in the expression levels of GRP78、CHOP and p-eNOS among the four groups ( F=32.39, 68.66, 13.12, all P<0.01). The expression levels of GRP78 and CHOP protein in TM group were higher than those of Control group (both P<0.05), while the expression level of p-eNOS was lower than that of Control group ( P<0.01). The expression levels of GRP78 and CHOP protein in NAC+ TM group were lower than those of TM group (both P<0.05), while the expression level of p-eNOS was higher than that of TM group ( P<0.01). There was no significant difference in the expression level of caspase-12 protein among the four groups ( F=0.33, P>0.05). Laser confocal showed that there was significant difference in the average fluorescence intensity of ROS among the four groups ( F=77.66, P<0.01). The average fluorescence intensity of ROS in TM group (32.67±1.53) was higher than that in Control group (12.67±2.08) and NAC+ TM group (18.33±1.53) (both P<0.01). Colorimetry showed that there were significant differences in the activity of SOD and the concentration of MDA among the four groups ( F=40.53, 34.99, both P<0.01). The results of colorimetry showed that the activity of SOD in TM group((41.60±1.53)U/mg) was lower than that in Control group((65.39±4.60)U/mg) and NAC+ TM group((58.72±1.64)U/mg)(both P<0.01). The concentration of MDA in TM((2.27±0.11)μmol/mg) group was higher than that in Control group((1.39±0.13)μmol/mg) and NAC+ TM group((1.44±0.11)μmol/mg) (both P<0.01). Conclusion:NAC can reduce Tm-induced apoptosis of cerebral micro-vascular endothelial cells, which may be related to its inhibition of ERS/ OS-related pathways.
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Objective:To investigate the preventive effects of intravenous N-acetylcysteine(NAC)administration on contrast-induced nephropathy(CIN)following coronary intervention in elder patients with coronary heart disease(CHD)complicated with moderate to severe renal dysfunction.Methods:In this retrospective study, 242 elderly patients with CHD and moderate to severe renal insufficiency hospitalized in the Department of Cardiology of the First Affiliated Hospital of Nanjing Medical University and undergone coronary angiography from January 2018 to February 2022 were included and divided into two groups: the treatment group(100 cases)receiving NAC plus a continuous intravenous drip of 0.9% sodium chloride solution before and after surgery and the control group(142 cases)treated with only a continuous intravenous drip of 0.9% sodium chloride solution.To ensure the comparability of important baseline data between the two groups, a 1∶1 propensity score matching analysis was used, and 70 patients in each group were finally included.Pre-and post-operative serum creatinine(Scr)and blood urea nitrogen(BUN)values were recorded, the endogenous creatinine clearance(Ccr)and estimated glomerular filtration rate(eGFR)were calculated, and the incidences of CIN and changes in renal function indicators were compared between the two groups.Results:After coronary intervention, the incidence of CIN in the treatment group was significantly lower than that in the control group(1/70 or 1.4% vs.8/70 or 11.4%, P=0.033). In the treatment group, Scr[(186.01±36.62)μmol/L vs.(195.84±36.39)μmol/L, t=4.957, P<0.001]and BUN[(13.97±2.89)mmol/L vs.(14.84±2.85)mmol/L, t=5.206, P<0.001]decreased, while Ccr[(31.84±6.54)ml/min vs.(30.08±5.65)ml/min, t=-5.076, P<0.001]and eGFR[(31.60±6.93)ml·min -1·1.73m -2vs.(29.82±5.92)ml·min -1·1.73m -2, t=-5.200, P<0.001]increased, compared with pre-operative levels.In the control group, Scr[(186.65±27.28)μmol/L vs.(182.53±22.08)μmol/L, t=-1.783, P=0.079]and BUN[(17.57±3.33)mmol/L vs.(17.13±3.35)mmol/L, t=-2.234, P=0.029]increased, but Ccr[(30.57±6.37)ml/min vs.(31.06±6.01)ml/min, t=1.435, P=0.156]and eGFR[(30.76±6.46)ml·min -1·1.73m -2vs.(31.26±6.02)ml·min -1·1.73m -2, t=1.436, P=0.156]decreased, compared with pre-operative levels, and there was no significant difference except BUN(all P>0.05). Conclusions:For elderly patients with coronary heart disease complicated with moderate to severe renal insufficiency, the use of NAC before and after coronary intervention can reduce the risk of CIN and help improve renal function.
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Objective:To explore the protective effect and mechanism of the antioxidant N-acetylcysteine (NAC) regulating silent information regulator 3 (Sirt3) on acute kidney injury (AKI) in septic mice.Methods:Male C57BL/6 mice were randomly ( random number) divided into the sham operation group (sham), cecal ligation and perforation group (CLP), CLP + NAC (50 mg/kg) and CLP + NAC (100 mg/kg) groups, with 10 mice in each group. The mice were sacrificed 24 h after CLP, and blood and kidney tissue samples were collected. HE staining was used to evaluate the pathological damage of the kidney tissue of mice in each group. ELISA was used to detect serum creatinine (Scr), urea nitrogen (BUN), kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated apolipoprotein (NGAL) levels. Immunohistochemistry was used to detect the expression of Sirt3 protein in kidney tissue. RT-qPCR was used to detect the level of Sirt3 mRNA. Mitochondrial damage of renal tubular epithelial cells was observed under transmission electron microscope, and the mitochondrial density was calculated. Meanwhile, the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA) in the renal cortex were also detected. Results:Compared with the sham group, in the CLP group, the pathological damage of renal tissue was significantly aggravated ( P<0.001), and the levels of renal function indicators (Scr, BUN, KIM-1 and NGAL) were all increased significantly (all P<0.001). The protein and mRNA expression of Sirt3 were all significantly decreased (all P<0.001), the mitochondrial structure damage of renal tubular epithelial cells was increased, and the mitochondrial density was significantly decreased ( P<0.001). The levels of antioxidant enzymes (SOD, GSH-Px and CAT) in the renal cortex were all significantly decreased (all P<0.001), while the lipid peroxide MDA was significantly increased ( P<0.001). Compared with the CLP group, the renal injury score and renal function indexes (Scr, BUN, KIM-1 and NGAL levels) in the 50 mg/kg NAC pretreatment group were decreased, and the levels of SOD, GSH-Px and CAT in renal tissue were increased, but the differences were not significant. However, pretreatment with 100 mg/kg NAC significantly reduced the pathological damage of kidney tissue caused by CLP ( P<0.001), and significantly decreased the levels of Scr, BUN, KIM-1 and NGAL (all P<0.001). The expression of Sirt3 protein [(50.20±2.79) vs.(20.00±0.75), P<0.001] and mRNA [(0.57±0.07) vs. (0.41±0.07), P<0.001] were all significantly increased. The mitochondrial structure of renal tubular epithelial cells was more stable, and the mitochondrial density was significantly increased [(0.60±0.05) vs. (0.43±0.06), P<0.001]. The levels of SOD [(67.37±3.79) U/mg vs. (21.09±0.89) U/mg, P<0.001], GSH-Px [(265.61±9.61) U/mg vs. (180.00±3.31) U/mg, P<0.001] and CAT [(8.58±0.65) U/mg vs. (5.19±0.58) U/mg, P<0.001] were all significantly increased, while the expression level of MDA was significantly reduced [(40.36 ±1.79) vs. (83.81 ±1.70), P<0.001]. Conclusions:NAC can significantly reduce renal pathological damage, improve renal function, maintain mitochondrial structure stability and reduce oxidative stress levels in septic mice by up-regulating Sirt3 protein expression, and has a significant protective effect on CLP-induced AKI.
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La talidomida fue desarrollada e introducida al mercado por los laboratorios Grünenthal en 1953, siendo usada principalmente como sedante y también para el tratamiento de las náuseas durante el embarazo. Los informes dan cuenta de aproximadamente 10.000 niños que nacieron con focomelia, dando lugar a la denominada "tragedia de la talidomida", que obligó a su retiro del mercado en 1962. Luego de casi 60 años, es nuevamente utilizada en otros campos de la medicina, entre ellos, para el tratamiento de la lepra y del mieloma múltiple, debido a sus propiedades antinflamatorias, inmunomoduladoras y antiangiogénicas, con expresas advertencias sobre su utilización durante el embarazo; no obstante, con su nuevo uso han sido reportados múltiples efectos adversos, entre los que se encuentra la hepatitis aguda o crónica inducida por este fármaco. Se presenta el caso de una paciente de 34 años con lepra, que estaba en tratamiento con talidomida desde hacía 4 años para combatir las lesiones de piel asociadas a esta enfermedad. Presentó malestar general, vómito, pérdida de peso, artralgias, ictericia, edemas de miembros inferiores, ascitis, coluria y acolia. Se sospechó toxicidad por talidomida, por lo que se suspendió su uso, y se trató con ácido ursodesoxicólico y N-acetilcisteína con mejoría sintomática y de laboratorio, desde la primera semana hasta los 41 días de seguimiento. Las entidades clínicas para las cuales se aprobó talidomida en 1998, pueden traer nuevos problemas y desafíos clínicos. Este caso muestra hepatotoxicidad crónica por talidomida, situación que hasta el momento no se había reportado en la literatura.
Thalidomide was developed and introduced to the market by Grünenthal laboratories in 1953, being used mainly as a sedative and also for the treatment of nausea during pregnancy. Reports give account of approximately 10,000 children who were born with phocomelia, giving rise to the so-called "thalidomide tragedy", which forced its withdrawal from the market in 1962. After almost 60 years, it is usedagain in other fields of medicine, including the treatment of leprosy and multiple myeloma, due to its anti-inflammatory, immunomodulatory and anti-angiogenic properties, with clear warnings about its use during pregnancy; however, multiple adverse effects have been reported in patients with leprosy and multiple myeloma, including acute or chronic hepatitis. We present the case of a 34-year-old patient with leprosy, who had been on thalidomide therapy for 4 years to treat skin lesions associated with this disease. She presented general malaise, vomiting, weight loss, arthralgia, jaundice, lower limb edema, ascites, choluria and acholia. Thalidomide toxicity was suspected, so its use was suspended, and treatment with ursodeoxycholic acid and N-acetylcysteine was initiated, with symptomatic and laboratory improvement from the first week up until 41 days of follow-up. The new range of medical conditions for which thalidomide was approved for in 1998 may bring clinical challenges. This case shows chronic hepatotoxicity due to thalidomide, a situation that had not been reported previously in the literature.
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Humanos , Talidomida , Toxicidade , Acetilcisteína , Ácido Ursodesoxicólico , Hepatite , IcteríciaRESUMO
Resumen: El acetaminofén es un medicamento analgésico y antipirético considerado como seguro y eficaz. Debido a esto, en Colombia es de venta libre y ampliamente utilizado tanto en niños como en adultos. Por su fácil acceso, la intoxicación por acetaminofén es un evento frecuente, por lo que los médicos de atención primaria deben tener conocimiento acerca de su diagnóstico y manejo, además de los factores de riesgo para el desarrollo de falla hepática y las indicaciones para remitir a los pacientes a los servicios especializados. El objeto de este artículo es orientar al personal de atención primaria en salud acerca de la fisiopatología, el diagnóstico y el tratamiento de esta intoxicación.
Abstract: Acetaminophen is an analgesic and antipyretic medication considered safe and effective. Because of this, in Colombia it is freely available and widely used in both children and adults. Due to its easy access, acetaminophen intoxication is a frequent event, so primary care physicians must be knowledgeable about its diagnosis and management. In addition to the risk factors for the development of liver failure and the indications for referring patients to specialized services. The purpose of this article is to guide primary health care personnel about the pathophysiology, diagnosis and treatment of this intoxication.
Resumo: O acetaminofeno é um medicamento analgésico e antipirético considerado seguro e eficaz. Por isso, na Colômbia é over-the-counter e amplamente utilizado em crianças e adultos. Por seu fácil acesso, a intoxicação por acetaminofeno é um evento frequente, é por isso que os médicos da atenção primária devem estar cientes de seu diagnóstico e manejo. Além dos fatores de risco para o desenvolvimento de insuficiência hepática e indicações de encaminhamento aos pacientes para serviços especializados. O objeto deste artigo é guiar á equipe da atenção primária á saúde sobre a fisiopatologia, diagnóstico e tratamento dessa intoxicação.
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Resumen Introducción: La ototoxicidad por cisplatino es un evento muy frecuente y sus consecuencias producen mucho deterioro en los pacientes. El diagnóstico precoz es esencial, pues permitiría implementar apropiadamente estrategias para aminorar su efecto. Entre estas tenemos la N-acetilcisteína, un agente antioxidante que ha demostrado efecto otoprotector. Objetivo: Evaluar el rol otoprotector de N-acetilcisteína comparado con placebo, en pacientes con cáncer de cabeza y cuello tratados con cisplatino. Material y Método: Ensayo clínico aleatorizado, paralelo y controlado con placebo. Se incluyen pacientes con cáncer de cabeza y cuello que requieren tratamiento con cisplatino, dos ramas: un grupo control que recibe placebo y otro que recibe el fármaco. Se realizan audiometrías de altas frecuencias (6-16 kHz) antes, durante y una vez finalizado el tratamiento. Resultados: Se aleatorizaron 45 pacientes, 23 al grupo intervencional y 22 al grupo control. Se encontró una incidencia general de la ototoxicidad del 73%, un empeoramiento en relación con tiempo de medición, una detención y estabilización del efecto ototóxico en el grupo que recibió N-acetilcisteína, todas estas diferencias fueron significativas. Conclusión: La N-acetilcisteína no previene la ototoxicidad inducida por cisplatino, pero modifica su curso de instalación y progresión. No se registraron efectos adversos al uso del fármaco. El monitoreo audiológico precoz es esencial para identificar la ototoxicidad y ejercer acciones para modificar su curso y mejorar la calidad de vida.
Abstract Introduction: Cisplatin-induced ototoxicity is a very frequent event and its consequences can cause a lot of deterioration in patients. There are some strategies to reduce its effect, among these, N-acetylcysteine, an antioxidant agent, has shown otoprotective effect. Aim: To evaluate the effect of N-acetylcysteine on ototoxicity by chemotherapy-radiotherapy in patients with head and neck cancer, compared with placebo. Material and Method: Randomized, parallel design and placebo controlled clinical trial. Patients with head and neck cancer who require treatment with cisplatin were enrolled: a control group that receives a placebo and experimental group that receives the drug. High-frequency audiometries were performed before, during and after the treatment finalization. Results: Forty-five patients were randomized, 23 for the experimental group and 22 for control group. The investigators found an incidence of ototoxicity of 73%, a worsening in relation to the time of measurement and a stopping and stabilization of the ototoxic effect in the group that received N-acetylcysteine, all these differences were statistically significant. Conclusion: N-acetylcysteine does not prevent cisplatin-induced ototoxicity, but does modify its course of installation and progression. No adverse effects were registered in this trial. Early audiological monitoring is essential to identify ototoxicity and eventually modify its course and improve the quality of life.
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Humanos , Masculino , Pessoa de Meia-Idade , Acetilcisteína/uso terapêutico , Cisplatino/efeitos adversos , Ototoxicidade , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Cisplatino/uso terapêutico , Antineoplásicos/uso terapêuticoRESUMO
Ovarian graft may be the target of the biochemical effects of oxidative stress caused at the time of transplantation. In order to evaluate the effect of N-acetylcysteine on the ovarian graft, regarding the estrous cycle preservation, 50 female and virgin EPM-1 Wistar rats, weighing up to 250g, originating from CEDEME of UNIFESP, were kept in adequate sanitary conditions. receiving their own food and water. Daily vaginal smears were performed to identify the estrous phase for 8 days. The animals were randomly distributed into 05 groups: 1st Group (GTx), saline was administered subcutaneously, 2nd (NAC 150mgKg), 3rd (NAC 300mg / Kg), 4th (NAC 600mg / Kg) and 5th (NAC 1200mg / Kg), that were administered NAC subcutaneously on the abdominal face, 60 minutes before left unilateral ovarian transplantation in retr operitoneum and contralateral oophorectomy for purposes of histomorphological analysis, with colpocytological evaluation. Euthanasia was performed by means of anesthetic lethal dose in half of the animals on the 4th postoperative day, with a single vaginal smear collection and euthanasia on the rest of the animals, between the 14th and 16th days, after the material was collected in order to define the estrus phase. It was evaluated in the graft that the animals exhibited in all groupsreturn of estrous cycle in the later phase of the post-transplant, with better definition of regular cycle in the highest dosages of N-acetylcysteine. N-acetylcysteine induced the return of the estrous cycle in the rats' ovarian graft , mainly in the highest dosage, proving its effectiveness in revascularization of the tissue after ischemia and reperfusion. (AU)
O enxerto ovariano pode ser alvo dos efeitos bioquímicos do stress oxidativo causado no momento do transplante. Com o objetivo de avaliar o efeito da N-acetilcisteína no enxerto ovariano, quanto à preservação do ciclo estral, foram utilizados 50 ratos EPM-1 Wistar, fêmeas e virgens, pesando até 250g, originários do CEDEME da UNIFESP, mantidos em adequadas condições sanitárias, recebendo ração própria e água. Realizados esfregaços vaginais diários para identificação da fase estral durante 08 dias. Os animais foram distribuídos aleatoriamente em 05 grupos: 1º Grupo (GTx), administrada solução salina via subcutânea, 2º (NAC 150mgKg), 3º (NAC 300mg/Kg), 4º (NAC 600mg/Kg) e 5º (NAC 1200mg/Kg), aos quais foi administrada NAC por via subcutânea em face abdominal, 60 minutos antes do transplante unilateral esquerdo do ovário em retroperitônio e à ooforectomia contra-lateral para fins de análise histomorfológica, com avaliação colpocitológica. A eutanásia foi realizada por meio da dose letal do anestésico em metade dos animais no 4º dia de pós-operatório, realizado única coleta de esfregaço vaginal e a eutanásia no restante dos animais, entre o 14 º e 16º dia, após a coleta do material para definição da fase estro . Foi avaliado no enxerto que os animais apresentaram em todos os grupos retorno de ciclo estral na fase mais tardia do pós-transplante, com melhor definição de ciclo regular nas dosagens mais elevadas de N-acetilcisteína. A N-acetilcisteína induziu o retorno do ciclo estral no enxerto ovariano de ratas, principalmente na maior dosagem comprovando sua eficácia na revascularização do tecido após isquemia e reperfusão. (AU)