Evaluation of epirubicin-induced acute oxidative stress toxicity in rat liver cells and mitochondria, and the prevention of toxicity through quercetin administration.
Anticancer therapy with epirubicin (EPI) results in acute hepatotoxicity, likely due to the generation of free radicals. However, the oxidative status of rat liver cells and mitochondria after EPI toxicity has not been investigated. In the present study, we first investigated the pro-oxidant effect of EPI on both hepatic cells and mitochondrial function. Injection of EPI into rats at a dose of 9mg/kg (cumulative dose in human chemotherapy), induced hepatic dysfunction, as revealed by a significant increase in serum glutamate oxaloacetate transaminases (SGOT) and glutamate pyruvate transaminases (SGPT). Oxidative stress in liver cells and mitochondria was provoked by EPI because a statistically significant reduction of catalase (CAT), superoxide dismutase (SOD) and cytosolic glutathione (GSH) levels, and a significant increase in malonedialdehyde (MDA) levels - an indicator of lipid peroxidation that can perforate biological membranes - were observed. Second, the protective effect of quercetin (QE) (0.33mg/kg) against EPI-induced oxidative stress was also investigated. Indeed, the pretreatment of rats with QE protected liver cells and mitochondria from oxidative stress. This treatment prevented hepatic dysfunction by maintaining normal levels of serum transaminases following the inhibition of their hepatic leakage by preventing lipid peroxidation. Thus, QE works through the prevention of cellular membrane perforation and the antioxidant defense system of mitochondria from liver cells, which represent compartments for the permanent production of reactive oxygen species (ROS) through the respiratory chain.
Kebieche
M
M
Phytochemistry and Pharmacology Laboratory, Faculty of Science, University of Jijel, Jijel, Algeria. mkebieche61@yahoo.fr
Lakroun
Z
Z
Lahouel
M
M
Bouayed
J
J
Meraihi
Z
Z
Soulimani
R
R
D000208:Acute Disease; D000284:Administration, Oral; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D015251:Epirubicin / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007275:Injections, Intravenous; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D015251:Epirubicin; D011794:Quercetin