Researchers have found that melatonin can protect kidney damage caused by obesity with diabetes.
Scientists from the University of Granada (UGR), the Hospital Universitario La Paz, Madrid, and the University of Texas, USA, have made a breakthrough in research into kidney damage and its progression towards kidney failure, which is closely related to obesity with Type 2 diabetes (known as diabesity) and its complications.
In two new studies, recently published in the Journal of Clinical Medicine and Pharmaceuticals, researchers found that melatonin protects the kidney damage caused by diabesity.
Reduction in cell damage
Using an obese and diabetic rodent model, the scientists demonstrated that chronic administration of melatonin at doses (10 mg/kg body weight/day) prevents mitochondrial and endoplasmic reticulum disruption, which play a critical role in the development and pathogenesis of kidney cell (nephron) damage, and its progression to renal failure.
These findings show that melatonin prevents the impairment of the function and dynamics of cellular mitochondria, decreasing the increased production of oxygen-free radicals (responsible for oxidative stress). It also halts the pathological alteration in the function of the endoplasmic reticulum (another cell cytoplasmic organelle), which, in conditions of abnormally high oxidative stress, is related to an increase in programmed cell death (of the nephron), leading to the loss of renal functionality, as a preliminary step to the development of renal failure and the need for haemodialysis or transplantation.
Lead author of the study, Ahmad Agil, researcher at the Department of Pharmacology of the UGR, explained: “Kidney damage is caused by the metabolic complications of obesity, such as diabetes, hypertension, blood lipid disorders, or fatty liver disease. Given that the prevalence of these pathologies (collectively recognised as metabolic syndrome) continues to increase, kidney damage and its progression over time to kidney failure has become a health problem that affects millions of people worldwide, with a great socioeconomic cost, requiring haemodialysis facilities and/or kidney transplant services, with the corresponding compatibility studies required.”
As well as highlighting the efficacy of melatonin in counteracting the two proposed mechanisms of renal damage, they also propose an alternative preventive treatment that would improve this renal function with a well-studied drug that has a very high safety profile such as melatonin. In the EU, melatonin must be prescribed by a doctor and is already administered in the treatment of insomnia.
The new findings have also been associated with an improvement in glomerular filtration rate and renal damage of the nephron, manifested in a decrease in creatinine clearance levels (the best marker of renal function), proteinuria, and in the improvement of renal structure, observed after histopathological study of the kidney.
These results are in line with those previously published by these researchers in the last ten years, demonstrating that the pharmacological administration of melatonin constitutes another new strategy in the therapeutic approach to diabesity and its complications (such as hepatic steatosis, hypertension, lipid alteration, etc.).
“Our main challenge is the application of melatonin and other strategies such as intermittent fasting in the field of medicine, especially to address the possibility of a treatment perspective for the aforementioned pathologies (diabesity and its complications) that involve an increase in oxidative stress, and mitochondrial damage and associated meta-inflammation (inflammation of metabolic origin),” Agil points out.
According to the results indicated by these researchers, melatonin could help treat kidney damage, which establishes the need to develop new clinical trials to test its effectiveness in humans. These results from preclinical models pave way for further investigations into melatonin, in order to determine its role in the maintenance of mitochondrial and endoplasmic reticulum homeostasis, and to a greater extent, if melatonin therapy would allow delaying or stopping progressive renal damage, by promoting its chronic pharmacological use in kidney repair and regeneration.