Amelioration of melatonin on oxidative stress and genotoxic effects induced by cisplatin in vitro.
In this study, we made an effort to evaluate the possible protective actions of melatonin on cisplatin-induced oxidative damage in mice brain homogenate and genotoxic effects in human lymphocytes under in vitro conditions. The tissue homogenate was divided into three parts. The first portion was kept as control treated with dimethyl sulphoxide (DMSO) (group 1) while the second and third portion were treated with 24 µg/g tissue cisplatin alone (group 2) and 24 µg/g tissue cisplatin in combination with 3 mM melatonin (group 3), respectively. We measured the oxidative stress biomarkers such as lipid peroxidation, 8-hydroxy 2' deoxyguanosine (8-OHdG) and antioxidant parameters such as reduced glutathione, superoxide dismutase, glutathione peroxidase, and glutathione reductase in brain homogenate. Likewise peripheral venous blood was collected from healthy donors and human lymphocyte culture was done using karyotyping medium. Cultures were divided into three groups. Group 1 was the control i.e. lymphocytes treated with DMSO 5 µg/mL. In group 2, lymphocytes were treated with 2 µg/mL cisplatin and group 3 with a combination of 2 µg/mL cisplatin and 0.3 mM melatonin. Incubation of tissue homogenates with cisplatin elevated the malondialdehyde and 8-OHdG levels which were then reversed by melatonin. Reduction in antioxidant parameters with respect to corresponding controls were also restored by melatonin treatment. Furthermore, supplementation of melatonin was found to modulate the chromosome damage elicited by cisplatin which was determined using Giemsa (GTG) banding and karyotyping. These findings suggest that melatonin improves the cellular function and helps them to survive in the belligerent environment created by free radicals.
Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695 012, Kerala, India.
Divya
D
Surendran
C S
CS
Geetha
P V
PV
Mohanan
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry; D002869:Chromosome Aberrations / Q000139:chemically induced; D002871:Chromosome Banding; D002945:Cisplatin / Q000633:toxicity*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007621:Karyotyping; D015227:Lipid Peroxidation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism
D016587:Antimutagenic Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D015415:Biomarkers; D008315:Malondialdehyde; D010088:Oxidoreductases; D005978:Glutathione; D008550:Melatonin; D002945:Cisplatin