Melatonin Treatment Improves Renal Fibrosis via miR-4516/SIAH3/PINK1 Axis

Dysregulation in mitophagy, in addition to contributing to imbalance in the mitochondrial dynamic, has been implicated in the development of renal fibrosis and progression of chronic kidney disease (CKD). However, the current understanding of the precise mechanisms behind the pathogenic loss of mitophagy remains unclear for developing cures for CKD. We found that miR-4516 is downregulated and its target SIAH3, an E3 ubiquitin protein ligase that reduces PINK1 accumulation to damaged mitochondria, is upregulated in the renal cortex of CKD mice. Here, we demonstrated that melatonin injection induces miR-4516 expression and suppresses SIAH3, and promotes PINK1/Parkin-mediated mitophagy. Furthermore, we demonstrated that melatonin injection attenuates the pathological features of CKD by improving mitochondrial homeostasis. Our data supports that mitochondrial autophagy regulation by activating miR-4516/SIAH3/PINK1 mitophagy signaling axis can be a viable new strategy for treating CKD.

Food deprivation and social inequality may lead to oxidative damage: a study on the preventive role of melatonin in the male rat reproductive system

Spermatogenic cells are susceptible to oxidative stress and apoptosis. Food deprivation (FD) has been reported as a stressor that could increase reactive oxygen species. In the present study, FD-induced oxidative stress and apoptosis, as well as the protective effects of melatonin, were evaluated in the testes. Wistar rats in the control group were fed a standard diet, whereas a sham group was administered saline as the melatonin vehicle. A third group received daily injections of melatonin (5 mg kg–1 bodyweight). These rats were further divided into four groups of rats that were either subjected to FD, FD + isolation, FD + melatonin injection and FD + melatonin injection + isolation. Testicular tissues were evaluated for malondialdehyde (MDA) and reduced glutathione (GSH) concentrations, as well as and DNA damage. FD increased MDA and reduced GSH concentrations, whereas melatonin treatment improved these parameters. Immunohistochemistry for capsase-3 and terminal deoxyribonucleotidyl transferase-mediated dUTP–digoxigenin nick end-labelling revealed that the number of apoptotic cells was increased in rats subjected to FD alone. Melatonin treatment offset the number of apoptotic cells following FD. The results provide evidence that FD can increase oxidative stress, leading to activation of apoptosis, and that melatonin has the ability to protect the testes against oxidative damage induced by FD.

Ефекти мелатоніну на когнітивні процеси та стан астроглії у щурів з експериментальним діабетом

There was investigated protective effect of chronic melatonin injection on the development of cognitive deficit in rats with streptozotocine induced diabetes. There were observed decrease of astrogliosis and of cognitive deficit in animals that were injected with melatonin. Presented results are evidence that melatonin can prevent the development of cognitive deficit in diabetic animals by decreasing oxidative stress level and astrogliosis inhibition.