Search

Drug induced hepatotoxicity is a major problem where phytochemicals hold promise for its abrogation. This study was carried out to explore cytoprotective potential of lupeol, a triterpene, against acetaminophen (AAP)-induced toxicity in rat hepatocytes. AAP exposure significantly (p<0.05) reduced cell viability, disturbed Bcl-2 family pro/anti-apoptotic protein balance, increased ROS production and altered redox homeostasis. It also induced mitochondria-mediated hepatocellular injury by significant mitochondrial depolarization, caspase-9/3 activation and subsequent DNA fragmentation. Our results suggest that lupeol pre-treatment effectively restored antioxidant enzyme levels, decreased lipid peroxidation, inhibited ROS generation and depolarization of mitochondria. Lupeol also attenuated mitochondria-mediated signaling pathway and DNA damage as evident from TUNEL assay and cell cycle studies leading to prevention of cytotoxicity. This study confirms the efficacy of lupeol, a food derived antioxidant, in abrogating ROS generation, maintaining redox balance and providing significant protection against mitochondria-mediated cell death during AAP-induced toxicity., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

This study was undertaken to evaluate the protective effect of thymoquinone (TQ) against acetaminophen-induced hepatotoxicity. Mice were given TQ orally at three different doses (0.5, 1 and 2mg/kg/day) for 5 days before a single hepatotoxic dose of acetaminophen (500 mg/kg i.p.). TQ supplementation dramatically reduced acetaminophen-induced hepatotoxicity, in a dose-dependent manner, as evidenced by decreased serum alanine aminotransferase (ALT) activities. Acetaminophen (500 mg/kg i.p.) resulted in a significant increase in serum ALT and total nitrate/nitrite, hepatic lipid peroxides and a significant decrease in hepatic reduced glutathione (GSH) and ATP in a time-dependent manner. Interestingly, supplementation of TQ (2mg/kg/day) for 5 days before acetaminophen administration resulted in reversal of acetaminophen-induced increase in ALT, total nitrate/nitrite, lipid peroxide and a decrease in GSH and ATP. Moreover, TQ did not affect acetaminophen-induced early decrease in hepatic GSH indicating lack of the effect on the metabolic activation of acetaminophen. In conclusion, TQ is effective in protecting mice against acetaminophen-induced hepatotoxicity possibly via increased resistance to oxidative and nitrosative stress as well as its ability to improve the mitochondrial energy production., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Extracts of Boerhaavia diffusa leaves were evaluated for antioxidant and hepatoprotective properties in the acetaminophen-induced liver damage model. Antioxidative evaluation of ethanolic extract gave total phenolic content, total flavonoid content, vitamin C content and vitamin E content and the levels of selenium and zinc as 6.6+/-0.2mg/g tannic acid equivalent, 0.092+/-0.003 mg/g quercetin equivalent, 0.21+/-0.03 mg/g, 0.054+/-0.002 mg/g, 0.52+/-0.05 ppm and 9.28+/-0.16 ppm, respectively. The DPPH scavenging capacity and the reductive potential were 78.32+/-2.41% and 0.65+/-0.02 mg/g ascorbic acid, respectively. Pretreatment with aqueous and ethanolic extracts decreased the activities of alkaline phosphatase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and the level of bilirubin in the serum that were elevated by acetaminophen. The two extracts also ameliorated the elevation in the activities of the enzymes in the liver. Acetaminophen intoxication led to reduction in serum and liver albumin levels which were not significantly increased by pretreatment with the extracts. The extracts also protected against acetaminophen induced lipid peroxidation. These results indicated that leaf extracts from B. diffusa possess hepatoprotective property against acetaminophen-induced liver damage which may be mediated through augmentation of antioxidant defenses., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Acetaminophen (APAP) can cause life-threatening renal damages and there is no specific treatment for APAP-induced renal damage. The aim of this study was to investigate the protective effects of curcumin (CMN) on APAP-induced nephrotoxicity. Nephrotoxicity was induced in male Wistar Albino rats by the administration of a single dose of 1000 mg/kg APAP intraperitoneally (i.p.). Some of these rats also received i.p. CMN (200mg/kg) at 30 min after the administration of APAP. Twenty-four hours after the administration of APAP, all the rats were sacrificed with a high dose of ketamine. Urea and creatinine levels were measured in the blood, and the levels of malondialdehyde (MDA) and glutathione (GSH), and antioxidant enzyme activity were determined in the renal tissue. Histopathological changes were studied. APAP administration caused elevated levels of renal MDA, and marked depletion of GSH levels and antioxidant enzyme activity, and deteriorated the renal functions as assessed by the increased plasma urea and creatinine levels as compared to control rats. CMN markedly reduced the elevated MDA levels, significantly increased the antioxidant enzyme activity and normalized the altered renal morphology in rats treated with APAP. CMN might be a potential candidate agent against APAP-induced nephrotoxicity, but further studies are required to identify this issue before clinical application becomes possible.

Tomato products containing lycopene are believed to be associated with decreased risk of chronic diseases including cancer, and its effects are suggested to be due to antioxidant effect of lycopene. The aim of this research was to study the effects of tomato extract on acetaminophen (APAP), amiodarone (ADN) and cyclosporine A (CsA)-induced liver, lung and kidney toxicity, respectively. Previous studies have shown that free radical reactions may play important roles in toxicity of these drugs. Rats received a single dose of APAP (750mg/kg, i.p.) before treatment with tomato extract (5mg/kg, oral) for seven consecutive days, ADN (100mg/kg, i.p.) plus tomato extract (5mg/kg, oral) for 10 consecutive days, or CsA (250mg/kg, i.p.) plus tomato extract (5mg/kg, oral) for 14 consecutive days. At the end of each treatment, the animals were sacrificed and the related organ tissues were collected for biochemical and histopathological examinations. Simultaneous treatment of tomato extract ameliorated tissue damage, biochemical indices, and oxidative stress parameters against APAP-induced acute hepatotoxicity, but had less beneficial effects on ADN-induced lung toxicity and little effect against CsA-induced nephrotoxicity. Therefore, tomato products may be beneficial for the prevention and therapy of toxicity induced by ADN and APAP.

Cuscuta chinensis is a commonly used traditional Chinese medicine to nourish the liver and kidney. Due to the poor water solubility of its major constituents such as flavonoids and lignans, its absorption upon oral administration could be limited. The purpose of the present study was to use the nanosuspension method to prepare C. chinensis nanoparticles (CN), and to compare the hepatoprotective and antioxidant effects of C. chinensis ethanolic extract (CE) and CN on acetaminophen-induced hepatotoxicity in rats. An oral dose of CE at 125 and 250 mg/kg and CN at 25 and 50mg/kg showed a significant hepatoprotective effect relatively to the same extent (P<0.05) by reducing levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. These biochemical assessments were supported by rat hepatic biopsy examinations. In addition, the antioxidant activities of CE and CN both significantly increased superoxide dismutase, catalase, glutathione peroxidase, and reduced malondialdehyde (P<0.05). Moreover, the results also indicated that the hepatoprotective and antioxidant effects of 50 mg/kg CN was effectively better than 125 mg/kg CE (P<0.05), and an oral dose of CN that is five times as less as CE could exhibit similar levels of outcomes. In conclusion, we suggest that the nanoparticles system can be applied to overcome other water poorly soluble herbal medicines and furthermore to decrease the treatment dosage.