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The delivery of selenium in a nano-form (Se-NPs) is a promising modality of treatment for various oxidative stress-induced diseases. This study aims to investigate the conceivable effects of selenium nanoparticles either alone (Se-NPs) or encapsulated with chitosan (Se-CS-NPs) on toxicity induced by CCl 4 in rats. Eighty albino rats were divided equally into eight groups. The first group was the placebo. The second group was a positive control, while the third and the fourth groups got orally (Se-NPs 5 mg/Kg) and (Se-CS-NPs 225 mg/Kg) respectively. The fifth and sixth groups were protective groups in which Se-NPs or Se-CS-NPs were given simultaneously. The seventh and eighth groups were therapeutic as they received either Se-NPs or Se-CS-NPs after stopping the CCl 4 injection for 4 weeks more. Our results showed that the protective and therapeutic groups showed an increase in caspase-3 gene expression with a decline in the expression of Bcl-2, Nrf2, and AFP genes. Histopathological and immunohistochemical investigations showed the role of selenium nanoparticles either alone or coated with chitosan in decreasing fibrotic marker collagen I positive reaction Selenium nanoparticles showed an excellent effect in counteracting the toxic effect of carbon tetrachloride on liver functions, inflammation reactions, and apoptosis process. Moreover, using selenium nanoparticles has a strong role in preserving the liver architecture with its normal constituents. No additional benefit was observed when the selenium nanoparticles were encapsulated with chitosan. [Display omitted] • Chitosan-Selenium Nanoparticles counteracted the toxic effects of CCl 4 on liver functions. • Chitosan-selenium nanoparticles reduced inflammation via regulation of NF-κB; Nrf2 signaling. • Chitosan-Selenium Nanoparticles influenced the apoptosis with high caspase-3 and low Bcl-2. • Chitosan-Selenium Nanoparticles decreased fibrotic markers as collagen I positive reaction. • Chitosan-Selenium Nanoparticles played a role in preserving liver normal constituents. [ABSTRACT FROM AUTHOR]

Background: The delivery of selenium in a nano-form (Se-NPs) is a promising modality of treatment for various oxidative stress-induced diseases., Objective: This study aims to investigate the conceivable effects of selenium nanoparticles either alone (Se-NPs) or encapsulated with chitosan (Se-CS-NPs) on toxicity induced by CCl 4 in rats., Methods: Eighty albino rats were divided equally into eight groups. The first group was the placebo. The second group was a positive control, while the third and the fourth groups got orally (Se-NPs 5 mg/Kg) and (Se-CS-NPs 225 mg/Kg) respectively. The fifth and sixth groups were protective groups in which Se-NPs or Se-CS-NPs were given simultaneously. The seventh and eighth groups were therapeutic as they received either Se-NPs or Se-CS-NPs after stopping the CCl 4 injection for 4 weeks more., Results: Our results showed that the protective and therapeutic groups showed an increase in caspase-3 gene expression with a decline in the expression of Bcl-2, Nrf2, and AFP genes. Histopathological and immunohistochemical investigations showed the role of selenium nanoparticles either alone or coated with chitosan in decreasing fibrotic marker collagen I positive reaction CONCLUSION: Selenium nanoparticles showed an excellent effect in counteracting the toxic effect of carbon tetrachloride on liver functions, inflammation reactions, and apoptosis process. Moreover, using selenium nanoparticles has a strong role in preserving the liver architecture with its normal constituents. No additional benefit was observed when the selenium nanoparticles were encapsulated with chitosan., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: The aim of present study was to find protective effect of α-asarone in cisplatin-induced hepatotoxicity in experimental rats. Materials and Methods: The rats were divided into 5 groups at randomly. Cisplatin was given at a dosage of 7.5 mg/kg to produce hepatotoxicity, and serum AST, ALT, total bilirubin, and albumin, as well as hepatic hydroxy proline (HP), reduced glutathione (GSH), and malondialdehyde (MDA), cytokines, and NO, were assessed. Finally, histological examination of liver tissue was performed (H&E staining). Results: Cisplatin treatment resulted in a reduction in body weight and a rise in liver weight in rats, while treatment with -asarone resulted in normal body and liver weight. Serum AST, ALT, total bilirubin, HP, GSH, MDA and cytokines were increased cisplatin rats. α-Asarone treated rats showed reduction in the oxidative stress as well as inhibited the release of cytokines in dose dependent manner and showed protection against hepatotoxicity. Cisplatin treated rat's shows pathological tissue structure, while rats treated with α- asarone shows normal structure of liver tissue. Conclusion: The study concludes that, α-asarone has protective effect against the hepatotoxicity induced by Cisplatin. [ABSTRACT FROM AUTHOR]

Abstract Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferroni’s post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.

The present study was conducted to investigate effect of pentoxifylline (PTX) on acute liver injury caused by galactosamine (D-Gal) in rats and the underlying mechanism involved in this setting. Moreover, we attempted to compare its effect to the well-established hepatoprotective agent, silymarin (SYM). The rats were randomly assigned 5 groups, control, PTX-treated (100 mg/kg, 3 weeks), SYM-treated (100 mg/kg, 3 weeks) and their combination. Hepatic injury was induced by intraperitoneal single dose injection of D-Gal (800 mg/kg). Hepatic functions parameters, including serum albumin and alkaline phosphatase (ALP) levels were determined. Antioxidants enzyme activities such as superoxide dismutase (SOD), catalase (CAT) as well as lipid peroxides and hepatic total nitrites were measured. Besides, histopathological examination was also performed using portions of liver tissues. Results showed that the liver injury induced by D-Gal was improved in the three pretreated groups to variable extents. Pretreatment with PTX prevented D-Gal-induced reduction of antioxidante enzyme activities, SOD and CAT, and attenuated the elevated malonaldahyde (MDA) level in hepatic tissue as marker of lipid peroxidation. In addition, pretreatment with PTX resulted in an increase in hepatic triglycerides, normalization of nitric oxide level, and lowering serum ALP activity as well as inhibited the decreased serum albumin level caused by D-Gal. These biochemical changes were reflected on attenuation the structural alterations of the liver integrity. Collectively, our data suggest that PTX exhibits a potential hepatoprotective effect against D-Gal-induced hepatotoxicity and this effect might be attributed to its antioxidant properties.

Substances of abuse induce alteration in neurobehavioral symptoms, which can lead to simultaneous exacerbation of liver injury. The biochemical changes of liver are significantly observed in the abused group of people using illicit drugs or drugs that are abused. A huge amount of work has been carried out by scientists for validation experiments using animal models to assess hepatotoxicity in cases of drugs of abuse. The risk of hepatotoxicity from these psychostimulants has been determined by different research groups. Hepatotoxicity of these drugs has been recently highlighted and isolated case reports always have been documented in relation to misuse of the drugs. These drugs induce liver toxicity on acute or chronic dose dependent process, which ultimately lead to liver damage, acute fatty infiltration, cholestatic jaundice, liver granulomas, hepatitis, liver cirrhosis etc. Considering the importance of drug-induced hepatotoxicity as a major cause of liver damage, this review emphasizes on various drugs of abuse and addiction which induce hepatotoxicity along with their mechanism of liver damage in clinical aspect as well as in vitro and in vivo approach. However, the mechanisms of drug-induced hepatotoxicity is dependent on reactive metabolite formation via metabolism, modification of covalent bonding between cellular components with drug and its metabolites, reactive oxygen species generation inside and outside of hepatocytes, activation of signal transduction pathways that alter cell death or survival mechanism, and cellular mitochondrial damage, which leads to alteration in ATP generation have been notified here. Moreover, how the cytokines are modulated by these drugs has been mentioned here. [ABSTRACT FROM AUTHOR]

Microcystins (MCs) are potent hepatotoxins produced by cyanobacteria in aquatic environments. MC-LR, a representative MC, strongly inhibits protein phosphatases 1 and 2A, leading to cell collapse in animal hepatocytes due to hyperphosphorylation of the cytoskeleton and apoptosis due to stimulation of the relevant systems. However, the molecular mechanisms and the metabolic pathways responsible for MC-LR toxicity are poorly understood. In the present study, we compared the cytotoxic effects of MC-LR in two cell lines: normal human hepatocytes (h-Nheps) and human hepatoma cell line HepG2. We also discussed the suitability of cellular assays for evaluating the toxicity of MCs. To obtain further insight into the molecular mechanism, the uptake, excretion, and intracellular distribution of MC-LR were analyzed using an antibody and assay kit targeting the catalytic subunit of protein phosphatase 2A (the PP2A assay kit). The responses toward MC-LR were distinctly different between the two cell lines. In HepG2 cells, MC-LR did not induce morphological change, did not reveal cytotoxicity, and accumulated to a lesser extent despite a slightly elevated expression of the MC transporter protein. MC-LR also did not alter the MC-binding potency of subcellular proteins. All these results indicate that HepG2 cells are inappropriate for the evaluation of MC-LR toxicity. The PP2A assay kits were useful not only for assessing PP2A-inhibitory potency, but also for determining the concentration of MCs in biological systems. [ABSTRACT FROM AUTHOR]

The gene and protein expression changes after exposure to a toxic compound might help elucidate its mechanism of action. In this paper we investigated the effect of carbon tetrachloride (CCl4) on the gene and protein expression in rat livers. Adult Wistar rats were administered CCl4 and livers were harvested 6 or 24 h thereafter. The analysis of mitochondrial proteins on 2D gels showed the upregulation of two proteins involved in stress (catalase and uricase). Among the downregulated proteins, enzymes related to the metabolism of lipids and aminoacids were affected. Additionally, α-2-macroglobulin and senescence marker protein, two proteins whose decrease in expression has been connected to hepatocyte damage, were decreased. Several of the upregulated genes are involved in stress response, DNA and protein damage, and repair. Genes coding for several enzymes involved in different metabolic pathways, including some P450, were downregulated in the treated animals. In conclusion, a single dose of CCl4 caused gene and protein expression changes that can be related to its mechanism of toxicity. Results from both technologies support previous publications and provide possible new toxicity markers. However, the correlation between gene and protein expression at a given time point is less apparent, partly as a result of different regulatory mechanisms between gene and protein expression. [Copyright &y& Elsevier]