Hepatoprotective effect of flavonoid rich fraction of Sesbania grandiflora: Results of In vivo, in vitro, and molecular docking studies

Background: Phytochemicals and their derivatives are promising target drugs for various ailments and have served as therapeutic agents for several decades. Using in vivo and in vitro models and molecular docking, this study investigated the pharmacological potential of a flavonoid-rich fraction of the ethanolic extract of Sesbania grandiflora (SG). Objectives: This research aimed to determine whether flavonoid-rich whole-plant extracts of SGs have any cytoprotective or in vivo hepatoprotective effects. Additionally, the study was intended to elucidate the molecular connections between the discovered flavonoid flavonols and PPAR? target proteins linked to liver problems, for which an in silico molecular docking investigation was performed. Materials and methods: To separate the flavonoid components, the entire Sesbania grandiflora plant was first extracted using ethanol as a solvent by soxhlet extraction. The resulting ethanolic extract was then fractionated. The cytoprotective and hepatoprotective properties were evaluated via in vitro and in vivo experiments. SGOT, SGPT, triglyceride, bilirubin, and total protein levels were used to evaluate hepatotoxicity in animal models. In vitro studies on Hepatocellular Carcinoma G2 (HepG2) cell lines have examined their cytotoxic effects and antioxidant activity. The most promising flavonoid-flavanol compounds were identified by conducting molecular docking studies against PPAR? target protein (PDB ID: 3VI8) using MOE software. Results: In vivo, the serum levels of SGOT, SGPT, total triglyceride and total bilirubin were measured in exper- imental animals treated with the flavonoid-rich ethanolic extract of SG. Significant reductions in the levels of these hepatic injury markers were observed, indicating the hepatoprotective potential of the extract. Elevated levels of liver biomarkers in the untreated group indicated liver injury or dysfunction. The treated groups showed significant restoration of these biomarkers, suggesting the hepatoprotective potential of SG. The IC50 value for the total flavonoid content of SG was 190.28 ?g/ml, indicating its safety in inhibiting HepG2 cell growth. Flavonoid treatment decreased cell viability but did not affect antioxidant parameters in hepatocytes. In addi- tion, SG restored the damaged hepatocyte architecture. Molecular docking studies revealed the binding affinities of flavonoids for PPAR?. These findings suggest that a promising lead candidate for the development of thera- peutic medicines against anti-TB drug-induced hepatotoxicity has been identified. Conclusion: Our findings demonstrate the hepatoprotective potential of the flavonoid-rich fraction of Sesbania grandiflora both in vivo and in vitro. This study provides valuable insights into its mechanism of action, high- lighting its promising therapeutic application in the management of liver disorders. This study highlights the hepatoprotective and cytoprotective potential of the total flavonoid-rich fraction of SG.

A study of the effect of antitubercular drugs on liver functions in newly diagnosed cases of tuberculosis during intensive phase of therapy in tertiary care hospital

Background: Antitubercular drugs are commonly associated with drug-induced liver injury (DILI), which can present as asymptomatic alterations in liver function test (LFT) to symptomatic hepatic injury and failure. Regular and frequent monitoring of LFT during intensive phase of therapy helps to identify early DILI and its complication. Aims and Objectives: The main objective was to evaluate the effects of antitubercular drugs on liver functions by early monitoring. Materials and Methods: A prospective observational study was conducted for 1 year among 97 newly diagnosed tuberculosis patients in tertiary care hospital. LFT was performed during baseline, at the end of 2nd week, and at end of intensive phase of treatment. Diagnosis of liver injury was based on DILI criteria and assessment of the clinical pattern of liver damage was done using “R value”. Results: Among 97 patients, 16 had experienced DILI and incidence was higher during the first visit. Aspartate aminotransferase (AST) and alanine aminotransferase were significantly altered during the first visit while AST and total bilirubin during the second visit. The number of parameters deranged was higher at the end of intensive phase than during the end of 2nd week. Cholestatic pattern (81.25 %) of liver injury was the most common type as per “R value”. According to DILI network severity index, the majority were categorized as “moderately- severe” and “moderate” during the first and second follow-up, respectively. Conclusion: The incidence of antitubercular drugs-induced liver injury was higher during the initial 2 weeks of treatment, but the derangement was more evident at the end of the intensive phase. Frequent and regular monitoring during the initial phase of treatment helps to detect early DILI which prevents the impending liver failure.

The Complementary View Of Chemical Induced Hepatotoxicity And Management: A Narrative Review

The concept of chemical induced toxicity could be found even in hunting age. Though the concept is older, its signi?cance is more remarkable in the current era. Present world is mixture of toxins, all of the living beings are part of it in actively or passively. The classical de?nition of the chemical toxicity is related to one chemical compound but, these days chemical compounds are common and hepatotoxicity is critical health issue. Hence the discussion of chemical induce toxicity is important, and trying to ?nd successful detoxi?cation strategy is crucial. Though having remarkable capabilities, the liver has limitation in advance damage and can worsen without proper management. Consequently, abstention from causative factors and symptomatic management is not enough to reverse the liver damage. Ayurveda, the practice of Indian system of medicine is a science addressed life from micro level to macro level, including all the concept that discuss in modern. In Ayurveda concept of visha (poison) is broad and informative and liver disease are comprehensively elaborated. Hence notion of contemporary science is crucial in the Chemical induced hepatotoxicity.

A case report on anti-tubercular agent induced hepatotoxicity

Hepatotoxicity is the serious adverse effect of tuberculosis treatment and it leads to the discontinuation of Anti-tubercular agent (ATT) causing increased drug resistance, morbidity and mortality. We report a 69 years old male patient with ATT induced hepatotoxicity.

Histopathological and biochemical effect of Liv-52 on rifampicin and isoniazid induced liver toxicity in adult albino rats

Background: Rifampicin and Isoniazid are two main medicinal drugs used as regimen in the treatment of Tuberculosis. These drugs induce hepatotoxicity. Liv-52, a polyherbal formulation has been shown to have clinical use in the treatment of liver disorders. The aim of this study was to investigate the histopathological and biochemical effects of Liv-52 on INH and RIF induced hepatotoxicity. Methods: Adult albino rats weighing 150g to 250g were used. A total of 24 rats were randomly assigned into 4 groups of 6 rats each. Group 1 served as negative control. Hepatotoxicity was achieved by administering 50 mg/kg/day of RIF and INH each as positive control. Hepatoprotective effect was determined by administering Liv-52 concurrently with positive control. Low dose Liv-52 and high dose Liv-52 was administered at (155 mg/kg/day and 207 mg/kg/day) respectively, concurrently with RIF and INH at (50 mg/kg) each orally daily. After 21 days, the albino rats were sacrificed humanely, liver harvested and blood samples taken for estimation of liver serum biomarkers. The livers were processed and stained with Haematoxylin and Eosin for histological examination. Significance levels of (p?0.05). Results: The three selected liver biochemical parameters (ALT, AST and ALP) significantly increased in positive control group relative to negative control. The hepatoprotective groups (especially the HD Liv-52 group) showed significant reduction in the biochemical parameters. The liver histopathological results confirmed the above findings. Conclusion: High dose Liv-52 significantly prevents hepatotoxicity induced by antitubercular therapy by inhibiting rise liver biochemical parameters and also ameliorating the deranged liver histomorphological features.

Effects of Ethyl Acetate Fraction of Mangifera haden Seeds on Carbon Tetrachloride Induced Hepatotoxicity in Albino Rats

The present study investigated the effects of ethyl acetate fraction of Mangifera haden seeds on carbon tetrachloride-induced liver damage in wistar albino rats. The phytochemical compositions and acute toxicity studies of crude extract and Mangifera haden seed fraction were determined using standard methods. Albino rats (60) randomly grouped into twelve of five rats each were used for this study. Determination of total bilirubin and protein, lipid peroxidation, liver enzymes marker, antioxidant enzymes, glutathione, lipid profile analysis and histological examination were carried out using standard methods. Phytochemical constituents of crude extract and ethyl acetate fraction of Mangifera haden seed showed that they contain relative amount of flavonoids, phenolics, saponins, tannins, terpenoids, triterpenes, alkaloids and coumarins. Liver injury was induced with carbon tetrachloride (CCl4) at a dose of 1.0 ml/kg body weight of the animals. All the CCl4 intoxicated rats displayed hyperlipidemia as shown by their elevated levels of serum total cholesterol (TC), triacylglycerol (TAG), low density lipoprotein (LDL), and reduction in high density lipoprotein (HDL) levels. The administration of ethyl acetate fraction of Mangifera haden seeds significantly (P = 0.05) lowered the levels of serum TC, TAG, LDL, and increased HDL levels. The level of serum malondialdehyde (MDA) significantly (P = 0.05) increased in the CCl4 group as compared to the normal and treated groups. The elevated level of serum MDA decreased (P = 0.05) significantly at the treatment of rats with 200, 400 and 600 mg/kg of ethyl acetate fraction. The rats treated with CCl4 produced significant (P = 0.05) increase in serum ALT, AST and ALP when compared to the normal group. Animals treated with varying doses of ethyl acetate fraction produced significant (P = 0.05) reduction of serum ALT, AST and ALP activities when compared to the CCl4-untreated group. The activities of hepatic antioxidant enzymes (SOD, CAT and GPx) and glutathione concentration significantly (P = 0.05) decreased in CCl4�-untreated group compared to the normal group. The decreased activities of the antioxidant enzymes and glutathione concentration in CCl4 intoxicated rats were ameliorated/modulated more effectively in rats treated with 200, 400 and 600 mg/kg ethyl acetate fraction of Mangifera haden seed. Total bilirubin (TB) concentrations significantly (P = 0.05) increased in CCl4-untreated group when compared to the normal group. Oral treatment of rats with varying doses (200, 400, 600 mg/kg) of ethyl acetate fraction caused a significant (P = 0.05) decrease in the serum TB levels. Administration of CCl4 showed a reduction in serum total proteins. Treatment of the animals with 200, 400 and 600 mg/kg of ethyl acetate fraction caused significant (P = 0.05) increase in serum total potein. Histological examination showed hepatoprotective properties of plant抯 fractions. The compounds found in the different fractions (ethyl acetate and n-hexane) of Mangifera haden seeds are 9-Octadecenoic acid (Z)-, methyl ester, (Z) 朞leic acid and so on. Therefore the medicinal importance of the plant is been established.

Development of an in vitro screening method for idiosyncratic hepatotoxic components in traditional Chinese medicine: a case study with Epimedii Folium and Psoraleae Fructus / 药学学报

Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.

High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Analysis of clinical and pathological characteristics of drug-induced live injury based on hepatotoxicity injury patterns / 临床与实验病理学杂志

Purpose To explore the clinical and pathologi-cal features and the relationships between pathological features and drugs of patients with drug-induced liver injury(DILI)based on the hepatotoxicity injury patterns.Methods The clin-ical data,laboratory indicators,drugs,and liver biopsy of 50 cases of DILI were collected,the expression of CK19 was detec-ted by immunohistochemistry EnVision two-step method,and the reticular scaffold of liver tissue was displayed by Reticular fiber staining.Results Among the 50 patients with DILI,there were 29 cases of hepatocellular DILI,11 cases of cholestatic DILI,and 10 cases of mixed DILI,respectively,with the hepatocellu-lar DILI accounting for the highest proportion(58％).7 catego-ries of drugs induced DILI,with herbal ranking first(52％).Different types of drugs could cause different types of DILI,with herbal induced 17 cases hepatocellular DILI(58.62％)and an-ti-infectious and anticancer drugs induced all 3 cases cholestatic DILI(27.27％).Different types of DILI displayed various pathological characteristics.Hepatocellular congestion,feathery degeneration,and small bile duct thrombosis primarily occur in cholestasis and mixed DILI,while bridging necrosis,sub-large and large necrosis were mainly seen in hepatocellular DILI.Conclusion Based on hepatotoxicity injury patterns,DILI ex-hibits a variety of clinical and pathological characteristics,and there is some relationship between pathological characteristics and drugs.Liver puncture pathological biopsy plays an important role in improving the diagnosis and treatment of DILI.

Study on the Mechanism of Hepatotoxicity Induced by Rhubarb Based on Network Pharmacology and Experimental Verification / 世界科学技术-中医药现代化

Objective The potential mechanism of hepatotoxicity induced by rhubarb was preliminarily explored by network pharmacology and verified by cell experiments.Methods Based on network pharmacology,component collection and target prediction are carried out through multiple databases.PPI network construction,GO enrichment analysis and KEGG pathway analysis were combined with software to systematically predict the mechanism of hepatotoxicity induced by rhubarb.The pathway information predicted by network pharmacology was verified by primary hepatocyte experiments and Western blot experiments.Results The results of network pharmacology showed that RH was the main component of hepatotoxicity induced by rhubarb.Seventeen core targets of hepatotoxicity induced by rhubarb were obtained.KEGG results suggested that DNA damage and apoptosis were one of the key mechanisms of hepatotoxicity induced by rhubarb.The results of primary hepatocytes and Western blot showed that RH could inhibit the viability of primary hepatocytes in a time-dose dependent manner.ABT and SFP can significantly reduce the toxicity of RH on primary liver cells in mice,and RFP can increase the toxicity of RH to mouse primary liver cells.Upregulation of γ-H2AX and PARP-1 protein in primary liver cells of mice after treatment with different concentrations of RH.Conclusion RH in rhubarb can significantly inhibit the viability of mouse primary hepatocytes,and its toxicity to mouse primary hepatocytes is mainly caused by the metabolic activation of RH by CYP 2C9.RH can activate PARP-1 protein,phosphorylate H2AX,induce DNA damage and apoptosis in mouse primary hepatocytes.

Lesión hepática inducida por medicamentos secundaria al consumo de esteroides androgénicos

El uso de esteroides anabólicos de forma ilícita es un problema en aumento caracterizado por la falta de conocimiento sobre los potenciales efectos secundarios a estos productos. El uso ilegal de los mismos ha llevado a un infra diagnóstico de los eventos adversos, dentro de los más frecuentes se ha encontrado la hepatotoxicidad. Se presenta el caso de un hombre adulto maduro deportista aficionado quien fue hospitalizado por ictericia y enfermedad hepática inducida por medicamentos en relación al uso de esteroides anabólicos en dosis elevadas. La prevención de la lesión hepática inducida por fármacos (DILI) implica educar a los pacientes que toman fármacos hepatotóxicos sobre su uso seguro, enseñar los signos y síntomas asociados con la lesión hepática, así como, la educación a la población vulnerable en prevenir la automedicación o el uso ilegal de estas sustancias.

The use of anabolic steroids in an illicit way is a growing problem characterized by the lack of knowledge about the potential side effects of these products. Their illegal use has led to under diagnosis of adverse events, among the most frequent of which was hepatotoxicity. We present the case of a mature adult male amateur athlete who was hospitalized for jaundice and drug-induced liver disease in relation to the use of high-dose anabolic steroids. The prevention of drug-induced liver damage (DILI) training the susceptible population about the dangers of self-medication and illegal drug use, as well as educating the vulnerable population to prevent self-medication. or the illegal use of these substances.

Investigation of the effect of Myricetin on Cisplatin-induced liver hepatotoxicity

SUMMARY OBJECTIVE: Cisplatin, a widely used anticancer agent, induces hepatotoxicity alongside organ damage. Understanding Cisplatin's toxicity mechanism and developing preventive measures are crucial. Our study explores Myricetin, a flavonoid, for its protective effects against Cisplatin-induced hepatotoxicity. METHODS: In our study, a total of 32 Wistar albino male rats were utilized, which were categorized into four distinct groups: Control, Myricetin, Cisplatin, and Myricetin+Cisplatin. For the histological assessment of hepatic tissues, hematoxylin-eosin and periodic acid Schiff staining were employed, alongside immunohistochemical measurements of TNF-α, interleukin-17, and interleukin-6 immunoreactivity. Additionally, aspartate transaminase and alanine transaminase values were examined by biochemical analysis. RESULTS: In the histological evaluation of the tissues, a normal healthy cell structure and a strong periodic acid Schiff (+) reaction were observed in the hepatocyte cells in the tissues of the Control and Myricetin groups, while intense eosinophilia, minimal vacuolization, congestion, and sinusoidal expansions were observed in the hematoxylin-eosin stainings, and a decrease in the positive reaction in the periodic acid Schiff staining was observed in the Cisplatin group. Consistent with these histological findings, an increase in TNF-α, interleukin-17, and interleukin-6 expressions (p<0.0001) and a concomitant increase in aspartate transaminase and alanine transaminase values were observed in the Cisplatin group. In the group protected by Myricetin, a significant improvement was observed in all these histological and biochemical values. CONCLUSION: Cisplatin induces notable histopathological alterations in the liver. In this context, Myricetin exhibits the potential to alleviate Cisplatin-induced damage by modulating histological parameters and biochemical processes.

Synthesis, characterization and protection effect of black rice anthocyanins nano-composite against hepatotoxicity induced by methotrexate in rats

Abstract The present study aimed to investigate the beneficial of prepared black rice anthocyanins nano-composite (An-AgNps) against hepatotoxicity induced by methotrexate (MTX) in rats. Anthocyanins nano-composite was prepared by silver as the metallic ion reduction and were characterized by IR and SEM. The rats in our experiment were divided into five groups. Serum lipid profile, serum transaminases (ALT and AST), ALP, LDH, TBA, GSH and SOD were examined. The results show that SEM of An-AgNps has average particle size from 70 to 130nm. In the group treated with MTX; TC, TG, LDL-c, ALT, AST, ALP, LDH and TBA levels were significantly (P0.05) increased than NC, while, HDL-c, SOD and GSH levels were significantly (P0.05) decreased. On the other hand, An-AgNps + MTX treated groups were reversed the levels of all biomarkers similar to NC. In conclusion, the results show that An-AgNps has a protective effect on MTX-induced hepatotoxicity and oxidative stress.

Resumo O presente estudo teve como objetivo investigar o benefício de nanocompósito de antocianinas de arroz preto preparado (An-AgNps) contra a hepatotoxicidade induzida por metotrexato (MTX) em ratos. O nanocompósito de antocianinas foi preparado a partir da prata por meio da redução do íon metálico e caracterizado por IR e SEM. Os ratos em nosso experimento foram divididos em cinco grupos, e foram examinados o perfil lipídico sérico, as transaminases séricas (ALT e AST), ALP, LDH, TBA, GSH e SOD. Os resultados mostram que SEM de An-AgNps tem tamanho médio de partícula de 70 a 130 nm. No grupo tratado com MTX, os níveis de TC, TG, LDL-c, ALT, AST, ALP, LDH e TBA aumentaram significativamente (P 0,05) do que NC, enquanto os níveis de HDL-c, SOD e GSH diminuíram significativamente (P 0,05). Por outro lado, nos grupos tratados com An-AgNps + MTX, foram revertidos os níveis de todos os biomarcadores semelhantes ao NC. Em conclusão, os resultados mostram que o An-AgNps tem um efeito protetor contra a hepatotoxicidade induzida pelo MTX e o estresse oxidativo.

Hepatotoxicidad por tamsulosina / dutasterida: reporte de un caso probable

La tamsulosina y dutasterida son medicamentos ampliamente usados como tratamiento de la hipertrofia benigna de próstata. teniendo un buen perfil de seguridad. Existen escasos reportes de injuria hepática asociado al uso de tamsulosina; sin embargo, no hay reportes de toxicidad hepática por el uso de dutasterida y del uso combinado de tamsulosina/dutasterida. Se presenta el caso de un varón de 64 años quien desarrolla injuria hepática tras el uso combinado de tamsulosina/dutasterida, desarrollando un patrón de daño hepatocelular y clínica de hepatitis aguda. Se realizo descarte de patología hepática viral, autoinmune y enfermedades metabólicas de depósito, así como de patología biliar mediante ecografía abdominal y colangioresonancia. En la evaluación de causalidad, presentó CIOMS-RUCAM: 6 puntos (probable) y Naranjo: 4 puntos (posible). El paciente presentó respuesta clínica y laboratorial luego de suspender el medicamento.

Tamsulosin and dutasteride are drugs widely used to treat benign prostatic hypertrophy. having a good safety profile. There are few reports of liver injury associated with the use of tamsulosin; however, there are no reports of hepatic toxicity from the use of dutasteride and the combined use of tamsulosin/dutasteride. We present the case of a 64-year-old man who developed liver injury after the combined use of tamsulosin/dutasteride, developing a pattern of hepatocellular damage and acute hepatitis symptoms. Viral, autoimmune, and metabolic storage diseases of the liver were ruled out, as well as biliary pathology by means of abdominal ultrasound and resonance cholangiography. In the causality evaluation, CIOMS-RUCAM presented: 6 points (probable) and Naranjo: 4 points (possible). The patient presented a clinical and laboratory response after discontinuing the drug.

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.

Investigation of the protective effect of boric acid against hepatotoxic and nephrotoxic injury induced by acrylamide in rats / Investigación del efecto protector del ácido bórico contra lesiones hepatotóxicas y nefrotóxicas inducidas por acrilamida en ratas

SUMMARY: To investigate if the administration of boric acid (BA) would exert any protective effect against possible nephrotoxicity and hepatotoxicity induced by the exposure to acrylamide (ACR) in rats. In our study, we used a total of 28 rats that were divided into four equal groups. Group 1: the control group which was not treated with any procedure. Group 2: the ACR group that was administered ACR 50 mg/kg/day via intraperitoneal (i.p) route for 14 days. Group 3: the BA group that was administered BA 200 mg/kg/ day via gavage via peroral (p.o) route for 14 days. Group 4: the ACR+BA group that was administered BA simultaneously with ACR. Total antioxidant and oxidant (TAS/TOS) capacities were measured in all groups at the end of the experiment. In addition, the specimens obtained were evaluated with histopathological examination. Studies showed that the ACR and ACr+BA groups were not significantly different in terms of hepatic TAS level while the TOS level was higher in the ACR group than the ACR+BA group. The groups did not show any significant difference regarding renal TAS and TOS levels. In the histopathological examination of the hepatic tissue, the histopathological injury score of the ACR group was significantly higher than those of the other groups whereas it was significantly lower in the ACR+BA group than the ACR group. Our study concluded that Boric acid had a protective effect against acrylamide- induced hepatotoxicity, but not against nephrotoxicity.

El objetivo de este estudio fue investigar si la administración de ácido bórico (BA) ejercería algún efecto protector frente a la posible nefrotoxicidad y hepatotoxicidad inducida por la exposición a acrilamida (ACR) en ratas. En nuestro estudio, utilizamos un total de 28 ratas que se dividieron en cuatro grupos iguales. Grupo 1: grupo control que no fue tratado. Grupo 2: grupo ACR al que se le administró ACR 50 mg/kg/día por vía intraperitoneal (i.p) durante 14 días. Grupo 3: grupo BA al que se le administró BA 200 mg/kg/día por sonda por vía peroral (p.o) durante 14 días. Grupo 4: grupo ACR+BA al que se administró BA simultáneamente con ACR. Las capacidades antioxidantes y oxidantes totales (TAS/TOS) se midieron en todos los grupos al final del experimento. Además, los especímenes obtenidos fueron evaluados con examen histopatológico. Los estudios demostraron que los grupos ACR y ACr+BA no fueron significativamente diferentes en términos del nivel hepático de TAS, mientras que el nivel de TOS fue mayor en el grupo ACR que en el grupo ACR+BA. Los grupos no mostraron ninguna diferencia significativa con respecto a los niveles renales de TAS y TOS. En el examen histopatológico del tejido hepático, la puntuación de lesión histopatológica del grupo ACR fue significativamente mayor que la de los otros grupos, mientras que fue significativamente menor en el grupo ACR+BA que en el grupo ACR. Nuestro estudio concluyó que el ácido bórico tiene un efecto protector contra la hepatotoxicidad inducida por acrilamida, pero no contra la nefrotoxicidad.

Supplementation of Madhuca longifolia Seed oil augments diclofenac-induced organ toxicities: A biochemical and histopathological approach-Supplemenntary data

Diclofenac medication has been extensively used for anti-inflammatory, anti-pyretic, and analgesic actions. Its abiding usage and overdose have induced toxicity and harmful effects on the liver, kidney, and gastrointestinal tract. The research aims to scrutinize the protective effect of Madhuca longifolia seed oil against diclofenac-induced toxicity in female Wistar albino rats. A period of 10 days of study was aimed at 7 groups; Group 1 was assigned as normal control. Group 2 has been administered diclofenac (50 mg/kg b.w. /day, i.p.) only on the last two days of each study period. Group 3 and Group 4 have been pre-treated with 1 mL, and 2 mL of Madhuca longifolia seed oil, respectively, and diclofenac was induced as per Group 2. Group 5 was treated with the standard drug silymarin and diclofenac. Group 6 and Group 7 were given 1 mL and 2 mL of Madhuca longifolia seed oil alone. After the study period, parameters like liver enzyme markers, renal enzyme markers, and antioxidants were measured, and tissue samples were analyzed for histopathological changes. The results proved that pre-treatment of 1 mL of Madhuca longifolia seed oil has efficacy against diclofenac-induced toxicity.

Supplementation of Madhuca longifolia Seed oil augments diclofenac-induced organ toxicities: A biochemical and histopathological approach

Diclofenac medication has been extensively used for anti-inflammatory, anti-pyretic, and analgesic actions. Its abiding usage and overdose have induced toxicity and harmful effects on the liver, kidney, and gastrointestinal tract. The research aims to scrutinize the protective effect of Madhuca longifolia seed oil against diclofenac-induced toxicity in female Wistar albino rats. A period of 10 days of study was aimed at 7 groups; Group 1 was assigned as normal control. Group 2 has been administered diclofenac (50 mg/kg b.w. /day, i.p.) only on the last two days of each study period. Group 3 and Group 4 have been pre-treated with 1 mL, and 2 mL of Madhuca longifolia seed oil, respectively, and diclofenac was induced as per Group 2. Group 5 was treated with the standard drug silymarin and diclofenac. Group 6 and Group 7 were given 1 mL and 2 mL of Madhuca longifolia seed oil alone. After the study period, parameters like liver enzyme markers, renal enzyme markers, and antioxidants were measured, and tissue samples were analyzed for histopathological changes. The results proved that pre-treatment of 1 mL of Madhuca longifolia seed oil has efficacy against diclofenac-induced toxicity.

Cow Urine Extract of Nicotiana tabacum Leaf Portends Hepatotoxicity in Male Wistar Rats

Aims: The toxicological effects of single and repeated doses of aqueous extract (AE) and cow urine extract (CUE) of Nicotiana tabacum leaf on the liver and kidney function indices of male Wistar rats were investigated. Study Design: Thirty-five male rats were randomized into seven groups (n=5). The control group received 0.5 mL of distilled water, groups A and B received 8 mg/kg body weight (BW) of CUE and AE respectively, once daily; groups C and D received 16 mg/kg BW of CUE and AE respectively, thrice a day (TD); groups E and F received 32 mg/kg BW of CUE and AE respectively, TD.The administration was oral and lasted for 28 days. Place and Duration of Study: The study was carried out at Summit University, Offa, Nigeria between June 2019 and August 2019. Methodology: Thirty-five male rats were randomized into seven groups (n=5). The control group received 0.5 mL of distilled water, groups A and B received 8 mg/kg body weight (BW) of CUE and AE respectively, once daily; groups C and D received 16 mg/kg BW of CUE and AE respectively, thrice a day (TD); groups E and F received 32 mg/kg BW of CUE and AE respectively, TD. Results: The result revealed no significant difference in the activities of the ALP, and GGT but a significant increase in the ACP, ALT, and AST activities in both tissues and serum. Furthermore, there was a significant decrease in albumin concentration of rats in all the groups except group B when compared with the control rats. Liver and kidney histology revealed minimal lymphocytic infiltration with no sign of medium-term systemic damage. Conclusion: The study suggests no nephrotoxicity of AE and CUE at all doses administered, but probable hepatotoxicity at higher and repeated doses of both extracts except at the single dose of 8 mg/kg BW of AE.

Chemical and Biological Evaluation of Bakeries Produced from Golden Berries

This investigation was performed with the purpose of researching the influence of pizza containing dried golden berry fruits (DGBF) at different doses against carbon tetrachloride - induced hepatotoxicity in rats. The study shows phenols content of golden berry. 25 male rats were used in the biological investigation. Rats were divided into five groups (5 rats in group) the investigation was 12 weeks. The first group (negative group) was given a basal diet and the second group (G2, G3, G4, and G5) was injected intramuscularly with carbon tetrachloride 2 ml/kg BW (50% v/v in liquid paraffin) weekly to induce hepatotoxicity. After the injury, group G3, G4 and G5 fed on 50% basal diet supplemented with 50%pizza containing 5, 10 and 15% DGBF. Findings indicate that DGBF had a high antioxidant activity, total phenol, flavonoids, ascorbic acid and carotenoids content. Rats fed 50% pizza containing (5,10 and 15%) DGBF had a lower serum total cholesterol, LDL cholesterol, triglyceride, urea, uric acid, creatinine, GOT, GPT, MDA and SOD compared to rats fed simply the basal diet (positive control). The DGBF was added to the pizza with different proportions, and its sensory properties were evaluated, and all proportions were proper to the panelists, compared to the control. The findings of this work suggest that golden berries could be used to treat and prevent hepatotoxicity patients.