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Acetaminophen (APAP) in high doses causes acute liver injury and acute liver failure. Ethyl gallate (EG) is a natural polyphenol, possessing antioxidant, anti-inflammatory, and anti-microbial properties. Therefore, in this study, we evaluated the protective role of EG against APAP-induced acute liver injury in mice. Acute liver injury was induced by a single dose of APAP (400 mg/kg., i.p.). In separate groups, EG (10 mg/kg), EG (20 mg/kg), and N-acetylcysteine (NAC; 1200 mg/kg., i.p.) were administered concurrently with APAP. The mice were sacrificed after 24 h of treatment. Liver marker enzymes of hepatotoxicity, antioxidant markers, inflammatory markers, and histopathological studies were done. APAP administration caused a significant elevation of marker enzymes of hepatotoxicity and lipid peroxidation. APAP administration also decreased enzymic and nonenzymic antioxidants. Acute APAP intoxication induced nuclear factor κ B, tumor necrosis factor-α, interleukin-1, p65, and p52 and downregulated IκB gene expressions. Our histopathological studies have confirmed the presence of centrilobular necrosis, 24 h after APAP intoxication. All the above abnormalities were significantly inhibited in groups of mice that were concurrently administered with APAP + EG and APAP + NAC. Our in silico analysis further confirms that hydroxyl groups of EG interact with the above inflammatory proteins at the 3,4,5-trihydroxybenzoic acid region. These effects of EG against APAP-induced acute liver injury could be attributed to its antioxidative, free radical scavenging, and anti-inflammatory potentials. Therefore, this study suggests that EG can be an efficient therapeutic approach to protect the liver from APAP intoxication., (© 2023 John Wiley & Sons Ltd.)

Oxidative stress plays an important role in the pathogenesis of various chronic liver diseases (CLD) and increasing evidence have confirmed the contributory role of oxidative stress in the pathogenesis of drugs and chemical-induced CLD. Chronic liver injury is manifested as necrosis, cholestasis, fibrosis, and cirrhosis. Chronic administration of anti-tubercular, anti-retroviral, immunosuppressive drugs is reported to induce free radical generation during their biotransformation in the liver. Further, these reactive intermediates are said to induce profibrogenic cytokines, several inflammatory markers, collagen synthesis during the progression of hepatic fibrosis. Oxidative stress and free radicals are reported to induce activation and proliferation of hepatic stellate cells in the injured liver leading to the progression of CLD. Hence, to counteract or to scavenge these reactive intermediates, several plant-derived antioxidant principles have been effectively employed against oxidative stress and came out with promising results in human and experimental models of CLD. This review summarizes the relationships between oxidative stress and different liver pathogenesis induced by drugs and xenobiotics, focusing upon different chronic liver injury induced by alcohol, antitubercular drugs and hyperactivity of antiretroviral drugs in HIV patients, viral hepatitis infection induced oxidative stress., (Copyright © 2018 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

The protective effect of silibinin (SBN) against hepatic fibrosis induced by repeated intermittent administration of N-nitrosodimethylamine (DMN) was investigated in rats. Oral administration of SBN recovered body and liver weight loss and reversed the elevation of serum AST, ALT and ALP accompanied by their fall in the liver tissue in DMN-induced fibrotic rats. Severe oxidative stress induced in fibrotic rats was evidenced by two to three fold elevation in MDA and protein carbonyl levels associated with a fall in the activities of SOD and CAT in repeated DMN treatment and this adversity was protected by SBN post-treatment. Further, the fall in the activities of ATPases and increase in the levels of hydroxyproline and collagen observed in the liver tissue of DMN treated rats was prevented and reversed back toward normalcy by SBN post-treatment. Recovery of rat liver tissue against DMN-induced hepatocellular necrosis, inflammatory changes and hepatic fibrosis by SBN treatment is also confirmed by both H & E and Masson's trichrome stained histopathological evaluation of liver tissue. In conclusion, SBN exhibit hepatoprotective, antioxidant, free radical scavenging, membrane stabilizing and anti-fibrotic activity against DMN-induced hepatic fibrosis suggesting that it may be useful as a therapeutic agent toward amelioration of hepatic fibrosis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Benzene is a notorious toxicant that is responsible for a host of diseases including leukemia. Its concentration in the environment is increasing day-by-day due to excessive automobile use, accelerated industrial activities and cigarette smoke. The awareness on the harmful effects of benzene on health is limited and no antidote has been reported yet. In this study, an attempt has been made to find out a suitable remedy to overcome benzene toxicity in a living organism from a natural source with the seeds of the plant Moringa oleifera (MO). Thirty six Wistar rats were considered for the study and divided into six groups (n=6). While group I remained as control with normal animals, those in groups II - VI received benzene by oral route (800 mg/kg body weight) for 28 consecutive days. On day 29, the benzene-treated animals in groups III - VI received respectively the standard drug ascorbic acid (AA, 25 mg/kg body weight) and MO (50, 100 and 200 mg/kg body weight) for the following 7 days. Group II rats that received only benzene served as negative control without any treatment. On day 36, all the animals were sacrificed and vital organs liver and kidney were removed for studying lipid peroxidation (LPO) and antioxidant markers [Superoxide dismutase (SOD), Total reduced glutathione (TRG), Glutathione peroxidase (GPx) and Catalase (CAT)] in addition to histopathological changes in the tissues. The results of the study revealed that significant changes occurred in the above parameters due to benzene dosing to animals were reverted to near normal values on MO administration in the liver and kidney tissues as compared to untreated animals, suggesting MO's pro-active role in attenuating benzene toxicity. [ABSTRACT FROM AUTHOR]

Prolonged zidovudine (AZT) treatment in HIV-infected and AIDS patients is shown to induce liver toxicity leading to complications. Therapeutic regimen that could encounter this adverse effect is unavailable and management of toxicity is often symptomatic or is limited to withdrawal of therapy. In the present investigation, we evaluated the alleviating properties of silibinin (SBN), a flavanolignan obtained from Silybum marianum against subacute AZT-induced hepatotoxicity and oxidative stress in rats. AZT treatment (50 mg/kg body weight (b.w.) periorally (p.o.), daily for 45 days) caused highly significant increases in alanine transaminase, alkaline phosphatase, argininosuccinic acid lyase and bilirubin in serum. Oxidative stress is shown by a highly significant increase in lipid peroxidase and total carbonyl content and decrease in catalase and protein thiols in the liver tissue. Hyperlipidaemia is indicated by highly significant increase in total lipids and free fatty acid in serum. Evaluation of liver by haematoxylin and eosin staining shows parenchymal cell enlargement, inflammatory changes and increase in sinusoidal spaces. Simultaneous treatment of SBN (100 mg/kg b.w. p.o., daily for 45 days) significantly protected the liver against hepatotoxicity, oxidative stress and hyperlipidaemia induced by AZT, and this alleviating property is attributed to hepatoprotective, membrane-stabilizing, antioxidant and free radical scavenging properties of SBN. [ABSTRACT FROM AUTHOR]