Melatonin inhibits apoptosis and oxidative tissue damage in cisplatin-induced pulmonary toxicity in rats.

Abstract

Cisplatin is one of the most frequently used chemotherapeutics, which is known to cause both tumor and normal lung tissue damage through the generation of free radicals and cells apoptosis/necrosis. Melatonin is a neurohormone that regulates numerous physiological processes in the body both through receptor pathways and by maintaining tissue redox homeostasis. The extent of rat lung damage induced by cisplatin and the effects of melatonin on this process was determined based on the pathohistological changes and biochemical disturbances in tissue lipid peroxidation, protein carbonyl modification and in the activity of xanthine oxidase (XO), caspase-3 and DNases. Histopathological analysis of rat lung tissue obtained from animals that received cisplatin found them to be edematous, with significant deterioration of alveolar epithelium. These morphological changes are accompanied by a significant increase in all studied oxidative stress-related parameters, as well as with the activity of apoptosis-related enzymes. A five-day treatment with melatonin completely prevented a cisplatin-induced increase in oxidative stress-related parameters and in the activity of XO, caspase-3 and alkaline DNase. Also, the histopathological changes observed during microscopic analysis were much less pronounced than in the group that received cisplatin only. These results can potentially be connected with the ability of melatonin to inhibit the activity of XO, caspase-3 and alkaline DNase and/or its ability to scavenge free radicals, thus preventing lung damage induced by cisplatin.