Mitigation of oxidative stress in cyclophosphamide-challenged hepatic tissue by DL-α-lipoic acid

Abstract

The present study investigated the protective effect of DL-alpha-lipoic acid on the tissue peroxidative damage and abnormal antioxidant levels in cyclophosphamide (CP) induced hepatotoxicity. Male Wistar rats of 140 +/- 20 g were categorized into four groups. Two groups were administered CP (15 mg/kg body weight once a week for 10 weeks by oral gavage) to induce hepatotoxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight intraperitoneally once a week for 10 weeks; 24 h prior to the CP administration). A vehicle (saline) treated control group and a lipoic acid drug control group were also included. The extent of liver damage in CP-induced rats was evident from the increased activities of serum aminotransferases, alkaline phosphatase and lactate dehydrogenase; whereas lipoic acid pretreatment prevented the rise in these marker enzymes. We evaluated the changes in activities/levels of tissue enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and glucose-6-phosphate dehydrogenase) and non-enzymic (reduced glutathione, ascorbate and a-tocopherol) antioxidants along with malondialdehyde levels in the experimental groups. In CP-administered rats the antioxidant enzymes showed significantly depressed activities (p < 0.001, p < 0.01) and the antioxidant molecules also showed depleted levels (p < 0.001, p < 0.01), in comparison with the control group. However the extent of lipid peroxidation and the abnormal antioxidant status were normalized in lipoic acid pretreated rats. The present work highlights the efficacy of lipoic acid as a cytoprotectant in CP-induced hepatic oxidative injury.

Protective effects ofOriganum vulgareethanol extract against cyclophosphamide-induced liver toxicity in mice

“…Cellular mechanisms of toxicity are mediated by an increase in the free radicals through intracellular phosphoramide mustard and acrolein, the principle alkylating metabolites of CP (Tripathi & Jena, 2008). In the present study, CP administration damaged the liver, and this observation is consistent with the previous reports (Elkiran et al, 2007;Selvakumar et al, 2005). CP administration under different conditions and doses has been demonstrated to be an excellent model to produce the syndromes of both oxidative stress and hepatic damage (Mathew & Kuttan, 1997;Stankiewicz et al, 2002;Sulkowska et al, 1999).…”

Nano-Se attenuates cyclophosphamide-induced pulmonary injury through modulation of oxidative stress and DNA damage in Swiss albino mice

“…Cellular antioxidant defenses involving the enzymes, SOD, CAT, and GPx play an important role against ROS generation during oxidative stress and protect tissues including lung from oxidative damage [57][58][59][60]. SOD catalyzes dismutation of the superoxide anion to H 2 O 2 and O 2 .…”

Hepatoprotective activity of white horehound (Marrubium vulgare) extract against cyclophosphamide toxicity in male rats

“…Previous studies have shown that therapeutic doses of CP could be toxic to liver (Snover et al 1989;Sulkowska et al 2002). CP is metabolized via the hepatic P450 enzymatic system resulting in the formation of 4-hydroxycyclophosphamide and its tautomer aldocyclophosphamide which induce an oxidative stress by producing hydroxyl radicals and altering the antioxidant status of a cell (Selvakumar et al 2005). Other findings suggest that CP depresses antioxidant defense in liver while its metabolism generates superoxide anions and hydrogen peroxide (H 2 O 2 ) (Singh et al 2014).…”