Restraint stress abates the antioxidant potential of melatonin on dimethyl benz (a) anthracene (DMBA) induced carcinogenesis

Free radical involvement in initiation, promotion and progression of carcinogenesis, implicates that scavengers of free radicals may act as inhibitors in the carcinogenic process. Melatonin, an antioxidant was used in the present study to evaluate its effectiveness on skin carcinogenesis induced by DMBA both with and without chronic restraint stress (CRS). Fifty Swiss albino young male rats were divided into five groups of 10 rats each as controls, topical DMB alone, Pre CRS-DMBA, melatonin DMBA and Pre-CRS-DMBA-melatonin treated groups. After 18 weeks blood was collected along with liver and skin samples. These were used for antioxidant enzyme assay, DNA damage and fluorescent spectra analysis. Melatonin showed antioxidant potential in combatting DMBA induced skin carcinogenesis measured by free radical scavenging enzymes and in vivo antioxidant status, DNA damage. Sensitive detection of the DMBA induced micro biochemical changes was possible by fluorescent spectroscopy from the transformed ratio of fluorescent intensity (F1 530 nm/630 nm) otherwise found constant for normal tissues. By melatonin treatment this ratio was similar to control values. The decreased antioxidant biochemical parameters depicting oxidative stress were comparable to comet assay and fluorescent studies, endorsing the chemo-preventive efficacy of melatonin against skin carcinogenesis caused by DMBA. CRS pre-exposure diminished the chemo-preventive/antioxidant ability of melatonin and the results were same as DMBA alone treatment, showing stress affected both cancer development and chemoprevention. CRS decreased the antioxidant potential of melatonin. Hence, managing stress could be perceived in cancer chemoprevention. Further studies focusing on stress reduction are needed.