Amelioration of cisplatin-induced toxicity in mice by carotenoid meso-zeaxanthin

• Published in: Human & experimental toxicology Vol. 31; no. 7; pp. 710 - 717
• Main Authors: Firdous, AP, Kuttan, R
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.07.2012; Sage Publications; Sage Publications Ltd
• Subjects: Animals; Antineoplastic Agents - toxicity; Antioxidants; Biological and medical sciences; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Catalase - metabolism; Chemotherapy; Cisplatin - toxicity; Creatinine - blood; Glutathione - metabolism; Glutathione Peroxidase - metabolism; Hemoglobins - analysis; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Leukocyte Count; Male; Medical sciences; Mice; Oxidative Stress - drug effects; Pharmacology; Protective Agents - pharmacology; Rodents; Superoxide Dismutase - metabolism; Toxicity; Toxicology; Urea - blood; Xanthophylls - pharmacology; Zeaxanthins; cisplatin; Carotenoid; meso-zeaxanthin; Antineoplastic agent; Toxicity; Rodentia; Cisplatin; Zeaxanthin; Alkylating agent; Vertebrata; Mammalia; Mouse; Animal; Platinum II Complexes
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327111431707

Carotenoid meso-zeaxanthin ((3R, 3′S)-β, β-carotene-3,3′-diol [MZ]) was evaluated for its protective effect against cisplatin-induced nephrotoxicity in Swiss albino mice. Oral administration of MZ was started 5 days prior to cisplatin (16 mg/kg body weight, intraperitoneally as a single dose) injection. Animals in all groups were killed 72 h after cisplatin treatment. In serum, renal function markers like urea and creatinine, which were drastically elevated in cisplatin-treated control animals, were found to be decreased significantly by MZ pretreatment. Cisplatin-induced myelosuppression was also found to be significantly ameliorated by MZ as evident from the increase in white blood cell count, bone marrow cellularity and number of maturing monocytes in MZ-treated animals when compared with cisplatin alone-treated control animals. The levels of antioxidant enzymes—superoxide dismutase, catalase and glutathione peroxidase—as well as the glutathione level in the kidney were decreased after cisplatin treatment. But the levels were markedly increased by the carotenoid treatment in a dose-dependent manner. Addition of MZ was found to inhibit singlet oxygen produced by toluidine blue in vitro. Moreover, administration of MZ to the animals inhibited increased lipid peroxidation, conjugated dienes and hydroperoxides that are formed in the kidney by cisplatin administration. The results of histopathological analysis supported the protective potential of MZ against cisplatin-induced toxicity.