Glycyrrhizic acid: A phytochemical with a protective role against cisplatin-induced genotoxicity and nephrotoxicity

Aims: Glycyrrhizic acid (GA) is a main sweetening component of licorice roots and has been found to be associated with multiple therapeutic properties. In this study, we used GA as a protective agent against the clastogenic and nephrotoxic effects of cisplatin (CP). Main methods: Mice were given a prophylactic treatment of GA orally at doses of 75 and 150 mg/kg body weight for seven consecutive days before the administration of a single intraperitoneal dose of CP at 7 mg/kg body weight. The modulatory effects of GA on CP-induced nephrotoxicity and genotoxicity were investigated by assaying oxidative stress biomarkers, lipid peroxidation, serum kidney toxicity markers, DNA fragmentation, alkaline unwinding, and micronuclei and by histopathological examination of the kidneys. Key findings: A single intraperitoneal dose of cisplatin in mice enhanced renal lipid peroxidation, xanthine oxidase, and H2O2 generation; depleted glutathione content, activities of the anti-oxidant enzymes glutathione peroxidase, glutathione reductase, catalase, glutathione-S-transferase and quinone reductase; induced DNA strand breaks and micronucleus formation (p<0.001); and majorly disrupted normal kidney architecture. Pretreatment with GA prevented oxidative stress by restoring the levels of antioxidant enzymes at both doses. A significant dose-dependent decrease in DNA fragmentation, micronucleus formation (p<0.05), and the kidney toxicity markers BUN (p<0.001), creatinine (p<0.01), and LDH (p<0.001) and restoration of normal kidney histology was observed. Significance: Our study supports the claim that the phytochemical GA has the potential to attenuate the side effects of anticancer drug overdose. (C) 2011 Elsevier Inc. All rights reserved.