Antioxidant action of bixin against cisplatin-induced chromosome aberrations and lipid peroxidation in rats.
Cisplatin is one of the most active cytotoxic agents in the treatment of cancer, but has serious side effects, inducing nephrotoxicity and chromosome aberrations. In this study we evaluated the role of the carotenoid bixin on cisplatin-induced oxidative stress in Wistar rats through three markers of oxidative damage: chromosome aberrations, glutathione depletion and lipid peroxidation. The animals were divided into six treatment groups with six rats in each (n= 6). The dose of cisplatin (5.0 mg kg(-1)body wt.) was injected i.p. and bixin (2.5 or 5.0 mg kg(-1)body wt.) was given by gavage at 48, 24 h and 10 min before the cisplatin injection. The treatment with the highest dose of bixin resulted in a statistically significant reduction, by about 33%, in cisplatin-induced abnormal metaphases (P< 0.05). A single dose of cisplatin enhanced the formation of lipid peroxides in 29% and resulted in a 29% depletion in renal glutathione 24 h after cisplatin administration (P< 0.05). The pretreatment with bixin reduced the total number of chromosome aberrations, inhibited the increase in lipid peroxidation, and inhibited renal glutathione depletion induced by cisplatin. Since the pretreatment with bixin alone was safe, under the present experimental conditions, the results suggest that bixin may have future clinical application after further studies.
Silva
C R
CR
Depto Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Brazil. mdlpbian@usp.br
Antunes
L M
LM
Bianchi
M L
ML
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects; D002338:Carotenoids / Q000008:administration & dosage / Q000494:pharmacology*; D002869:Chromosome Aberrations; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D005503:Food Additives / Q000494:pharmacology*; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D000970:Antineoplastic Agents; D000975:Antioxidants; D005503:Food Additives; D017392:Thiobarbituric Acid Reactive Substances; D002338:Carotenoids; C004588:bixin; D005978:Glutathione; D002945:Cisplatin