Modulation of DiabetesInduced Oxidative Stress A

Authors: Mehmet Cemal Kahya Mustafa Nazıroğlu İshak Suat Övey

Publish Date: 2016/03/09

Volume: 54, Issue: 3, Pages: 2345-2360

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Abstract

Neuropathic pain and hippocampal injury can arise from the overload of diabetesinduced calcium ion Ca2+ entry and oxidative stress The transient receptor potential TRP melastatin 2 TRPM2 and TRP vanilloid type 1 TRPV1 are expressed in sensory neurons and hippocampus Moreover activations of TRPM2 and TRPV1 during oxidative stress have been linked to neuronal death Melatonin MEL and selenium Se have been considered potent antioxidants that detoxify a variety of reactive oxygen species ROS in neurological diseases In order to better characterize the actions of MEL and Se in diabetesinduced peripheral pain and hippocampal injury through modulation of TRPM2 and TRPV1 we tested the effects of MEL and Se on apoptosis and oxidative stress in the hippocampal and dorsal root ganglion DRG neurons of streptozotocin STZinduced diabetic rats Fiftyeight rats were divided into six groups The first group was used as control The second group was used as the diabetic group The third and fourth groups received Se and MEL respectively Intraperitoneal Se and MEL were given to diabetic rats in the fifth and sixth groups On the 14th day hippocampal and DRG neuron samples were freshly taken from all animals The neurons were stimulated with a TRPV1 channel agonist capsaicin and a TRPM2 channel agonist cumene hydroperoxide We observed a modulator role of MEL and Se on intracellular free Ca2+ concentrations current densities of TRPM2 and TRPV1 channels apoptosis caspase 3 caspase 9 mitochondrial depolarization reduced glutathione glutathione peroxidase lipid peroxidation and intracellular ROS production values in the neurons In addition procaspase 3 and 9 activities in western blot analyses of the brain cortex were also decreased by MEL and Se treatments In conclusion in our diabetes experimental model TRPM2 and TRPV1 channels are involved in the Ca2+ entryinduced neuronal death and modulation of this channel activity by MEL and Se treatment may account for their neuroprotective activity against apoptosis and Ca2+ entryPossible molecular pathways of involvement of melatonin and selenium in diabetesinduced apoptosis oxidative stress and calcium accumulation through TRPM2 and TRPV1 channels in the hippocampus and DRG neurons of rats The TRPM2 channel is activated by ADPribose and oxidative stress although it is inhibited by ACA The TRPV1 channel is activated by oxidative stress and capsaicin and it is blocked by capsazepine CPZ Diabetes can result in augmented ROS release in hippocampal and DRG neurons through polyol reactions leading to Ca2+ uptake through TRPM2 and TRPV1 channels Mitochondria were reported to accumulate Ca2+ provided intracellular Ca2+ rises thereby leading to the depolarization of mitochondrial membranes and release of apoptosisinducing factors such as caspase 3 and caspase 9 Melatonin and selenium reduce TRPM2 and TRPV1 channel activation through the modulation of polyol oxidative reactions and seleniumdependent glutathione peroxidase GSHPx antioxidant pathways

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