Cisplatin impairs antioxidant system and causes oxidation in rat kidney tissues: possible protective roles of natural antioxidant foods

Abstract

This study aims to elucidate the molecular mechanism(s) of cisplatin nephrotoxicity and the possible protective effects of antioxidant food supplementation on this toxicity. Twenty eight rats were used throughout the study. Cisplatin was administered intraperitoneally (i.p.) in a single dose (10 mg kg(-1)). Antioxidant food supplementation was started 3 days before cisplatin treatment. In each group (control, cisplatin, cisplatin plus dried black grape and cisplatin plus tomato juice), there were seven animals. Rats were killed 72 h after treatment. The kidneys were removed and prepared for biochemical and histopathological investigations. Oxidant (sensitivity to oxidation, xanthine oxidase enzyme and malondialdehyde level) and antioxidant (superoxide dismutase, glutathione peroxidase and catalase enzymes, and antioxidant potential value) parameters were measured in kidney tissues of the groups. Histopathological examination was also performed. Significant decreases were measured in the renal activities of catalase and glutathione peroxidase enzymes. There was, however, a significant increase in the activity of xanthine oxidase enzyme in the cisplatin-treated animals compared with the control group. The kidney tissue malondialdehyde levels were found to be increased, but sensitivity to oxidation and antioxidant potential values to be decreased in the cisplatin group. In the food supplemented groups, it has been observed that black grape eliminated oxidant stress by increasing antioxidant potential, but tomato did not. Histopathological examination results also revealed significant damage in the kidney tissues from the cisplatin-treated rats. In the black grape group, significant improvements were observed compared with the cisplatin group. In the tomato group, there were also some improvements but to a lesser degree compared with the black grape group. The results suggest that cisplatin treatment causes significant oxidant load to the kidneys through both xanthine oxidase activation and impaired antioxidant defense system, which resulted in accelerated oxidation reactions in the kidney tissue. It is proposed that supplementation of some foods such as black grape which has resveratrol as an antioxidant can provide significant protection against cisplatin nephrotoxicity.

Pretreatment with Oxygen Protects Rat Kidney from Cisplatin Nephrotoxicity

“…[9] Cisplatin causes significant oxidant loading to the kidney through both free radical formation and impaired antioxidant defense systems. [10] The hypothesis underlying the present study is that mild oxidative stress induced by oxygen pre-exposure [11] may enhance some endogenous defense mechanisms such as renal antioxidant systems and reduce subsequent cisplatin-induced kidney damage resulting from reactive oxygen species. Keeping this in view, we compared the degree of renal functional and structural injury in rats that were subjected to high-dose cisplatin administration with or without oxygen pretreatment.…”

Effects of grape consumption on plasma and erythrocyte antioxidant parameters in elderly subjects

“…Among them, black grape is a food with high antioxidant power (2,3) and it deserves special attention in this regard. In previous studies it was established that dried black grape may strengthen the antioxidant potential of the body and thus reduce some oxidant stress-induced health problems (4,5).…”

Effects of Different Doses of Hyperbaric Oxygen on Cisplatin-Induced Nephrotoxicity

“…[3,4] A number of antioxidants have been reported to reduce oxidative stress and prevent cisplatin nephrotoxicity. [5][6][7][8][9] Figure 1. Epithelial necrosis (short black arrow), cast formation, (long white arrow), and apoptotic cells (arrowhead) in the distal tubulus due to cisplatin nephrotoxicity (×200 HE; cisplatin group).…”

“…[3,4] Cisplatin is able to induce the formation of ROS and reduce the activity of antioxidant enzymes in renal tissue. [5][6][7][8][9] . The formation of excessive levels of ROS can lead to lethal or sub-lethal cellular damage.…”