Influence of melatonin on free radical-induced changes in rat pancreatic beta-cells in vitro

Free radicals may produce cytotoxicity to pancreatic islets under pathophys iological conditions. The aim of our in vitro investigations was to compare functional and morphological changes in pancreatic beta-cells induced by r eactive oxygen species (ROS) generated by alloxan or xanthine oxidase/hypox anthine (XO/HX), respectively. We demonstrate that short-term exposure to a lloxan or to XO/HX leads to a temporarily elevated insulin release from iso lated pancreatic islets, On application of alloxan, this effect is caused b y beta-cell necrosis and can be prevented by administration of melatonin, w hile in contrast, XO/HX did not lead to long-term morphological changes in the majority of the cells. Among the cells destroyed by alloxan, only necro sis could be detected, while in contrast, some apoptotic cells were identif ied by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) reaction and electron microscopic examinations of cell s treated with XO/HX. Melatonin was able to prevent the changes caused by a lloxan, but failed to influence the alterations caused by XO/HX. Using elec tron spin resonance and lipid peroxidation assay, respectively, it was conf irmed that melatonin effectively detoxifies hydroxyl radicals. Therefore, w e believe that hydroxyl radicals are the toxic principle of alloxan, but no t of XO/HX toxicity.