CHLOROPHYLLIN AMELIORATES THE NEPHROTOXICITY AND OXIDATIVE STRESS INDUCED BY CISPLATIN WITHOUT AFFECTING ITS ANTITUMOR ACTIVITY
Magda M. Noshy1, Hafez F. Hafez2, Akmal A. El-Ghor1 and Hanan R. Hamad1
1Department of Zoology, Faculty of Science, 2Pharmacology Unit, National Cancer Institute, Cairo University
Cisplatin is one of the most active agents in the treatment of cancer. However, it has severe side effects particularly nephrotoxicity. The nephrotoxic effect of cisplatin is closely associated with its ability to induce oxidative stress. The aim of the present study was to investigate the possible protective role of chlorophyllin (CHL), which is reactive oxygen species scavenger, against cisplatin induced nephrotoxicity and oxidative stress and also to evaluate its influence on the antitumor activity of cisplatin. The latter was administered to mice alone or after treatment with CHL. The mice were treated with CHL (2 or 6 mg/kg, i.p.) 1h before the administration of cisplatin (6 mg/kg, i.p.) and then sacrificed 24 h after treatment with the drug. Urea and creatinine levels in serum were estimated for renal function. Oxidative stress was evaluated using three markers of oxidative damage, superoxide dismutase (SOD) activity, glutathione (GSH) depletion and lipid peroxidation. The results showed that CHL pretreatment modulated the elevation of serum creatinine and urea levels, GSH depletion, inhibition of SOD activity and increase in lipid peroxidation induced by cisplatin. To evaluate the possible modification of the antitumor activity of cisplatin by CHL, we studied their interaction in Ehrlich ascites carcinoma (EAC) bearing mice. The results revealed that CHL did not reduce the antitumor activity of cisplatin. The current study suggests that CHL may improve the therapeutic effect of cisplatin.