Protective effects of increasing vitamin E and a doses on cisplatin-induced oxidative damage to kidney tissue in rats.
OBJECTIVE
Cisplatin (DDP, cis-diamminedichloroplatinium II) is one of the most potent chemotherapeutic antitumor drugs, but is able to generate reactive oxygen species (ROS) and it also inhibits the activity of antioxidant enzymes in renal tissue. In the present study, we investigated the preventive effect of 100, 200 and 400 mg/kg b.w. doses of vitamin E (VE), and 25, 50, and 100 mg/kg b.w. doses of vitamin A (VA) combination on malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH) levels and superoxide dismutase (SOD) activity in cisplatin-induced toxicity in rat kidneys. Our literature survey indicated a lack of any experimental study showing the beneficial effect of VA on cisplatin-induced MDA, NO, GSH and SOD changes. For this reason, we hoped that this study would provide a unique contribution in that respect.


METHODS
59 Wistar rats (11 to replace prematurely lost animals) were used. 48 evaluable rats were divided into 8 groups (n = 6 in each group): control group, DDP alone (5 mg/kg b.w.) group, 3 VE combination treatment groups of VE100+DDP, VE200+DDP, and VE400+DDP, and 3 VA combination treatment groups of VA25+DDP, VA50+DDP, and VA100+DDP. Kidney MDA, GSH, NO levels and SOD activities were determined for the assessment of oxidant-antioxidant balance.


RESULTS
While in the DDP group the tissue levels of MDA and NO were found to be significantly higher than in the control group, GSH levels and SOD activities were significantly lower. MDA and NO levels were found to be significantly lower and GSH levels and SOD activities significantly higher in the VE200+DDP and VE400+ DDP groups when compared with the DDP alone group. MDA and NO levels were found to be significantly lower in the VA50+DDP and VA100+DDP groups when compared with the DDP alone group. However, identical comparisons with the DDP alone group showed significantly higher GSH levels and SOD activities in the VA25+DDP, VA50+DDP, and VA100+DDP groups. Among the VE100+ DDP, VE200+DDP, and VE400+DDP groups, and VA25+ DDP, VA50+DDP, and VA100+DDP groups, MDA and NO levels decreased and GSH levels and SOD activities increased steadily and significantly as the doses of VE and VA increased.


CONCLUSIONS
These vitamins would be effective in protecting against cisplatin-induced tissue damage in rat kidneys. It is possible that the toxic effect of cisplatin is somehow minimized by a compensatory mechanism involving VE and VA via induction of antioxidant enzyme activities following intraperitoneal injection of DDP.
Dillioglugil
Meltem Ozlen
MO
Department of Medical Biochemistry, Kocaeli University, Faculty of Medicine, Kocaeli, Turkey. mozden@superonline.com
Maral Kir
Hale
H
Gulkac
Mehmet Dogan
MD
Ozon Kanli
Aylin
A
Ozdogan
Haci Kahya
HK
Acar
Oguz
O
Dillioglugil
Ozdal
O
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D000975:Antioxidants / Q000008:administration & dosage*; D015415:Biomarkers / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage*; D014810:Vitamin E / Q000008:administration & dosage*; D014815:Vitamins / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D000975:Antioxidants; D015415:Biomarkers; D014815:Vitamins; D014807:Vitamin D; D014810:Vitamin E; D009569:Nitric Oxide; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione; D002945:Cisplatin