Dr. Ahmad Agil. Photo credit: University of Granada
Scientists from the University of Granada (UGR), the Hospital Universitario La Paz (Madrid) and the University of Texas (USA) have taken an important step in the fight against kidney damage and its progression towards kidney failure, which is closely related to diabetes (obesity with type -2 diabetes) and its complications.
In two new studies recently published in the Journal of Clinical Medicine and Pharmaceuticals, researchers developed a model for obese and diabetic rodents and showed that melatonin protects against kidney damage from diabetes.
The scientists have shown that the chronic administration of melatonin in doses (10 mg / kg body weight / day) prevents disruption of the mitochondrial and endoplasmic reticulum, which plays a crucial role in the development and pathogenesis of renal cell damage (nephron) and its progression Kidney failure.
Thus, it has been shown that melatonin prevents the impairment of the function and dynamics of cellular mitochondria and reduces the increased production of free oxygen radicals (which are responsible for oxidative stress). It also prevents a pathological change in the function of the endoplasmic reticulum (another cytoplasmic cell organelle) which, under conditions of unusually high oxidative stress, is related to an increase in programmed cell death (the nephron) leading to the loss of kidney functionality as a preliminary step in the development of a Kidney failure and the need for hemodialysis or transplantation.
The studies, coordinated by the UGR, demonstrate the effectiveness of melatonin in curbing the progression of kidney damage mediated by mitochondrial damage and excessive stress on the endoplasmic reticulum.
As the lead author of this study, Ahmad Agil, a researcher in the Department of Pharmacology at UGR, says: “Kidney damage is caused by metabolic complications of obesity such as diabetes, high blood pressure, blood lipid disorders or fatty liver disease that the prevalence of these pathologies (collectively recognized as metabolic syndrome) continues to increase, Kidney damage and its progression to kidney failure over time have become a health problem affecting millions of people worldwide, with high socio-economic costs, requiring hemodialysis facilities and / or or kidney transplant services with the appropriate required compatibility studies. “
The importance of the work lies not only in the effectiveness of melatonin in counteracting the two proposed mechanisms of kidney damage (based on changing mitochondrial function and dynamics and endoplasmic reticulum (ER) function), but they also suggest an alternative preventive one Treatment that would improve this kidney function with a well-studied drug with a very high safety profile, such as melatonin, a drug that must be prescribed by a doctor in the EU and is already used to treat insomnia.
The new findings have also been linked to an improvement in glomerular filtration rate and kidney damage to the nephron, which was manifested in a decrease in creatinine clearance (the best marker of kidney function), proteinuria, and the improvement in kidney structure observed after histopathological examination the kidney.
These results are in agreement with those published by these researchers over the past 10 years and indicate that the pharmacological delivery of melatonin is another new strategy in the therapeutic approach to diabetes (central obesity and type 2 diabetes) and its complications ( such as liver steatosis, high blood pressure, lipid changes, etc.).
“Our main challenge is the application of melatonin and other strategies such as intermittent fasting in the medical field, particularly to investigate the possibility of a treatment prospect for the above pathologies (diabetes and its complications), which include an increase in oxidative stress, and mitochondrial damage and associated meta-inflammation (inflammation of metabolic origin), “says Agil.
According to the results, melatonin could help treat kidney damage, which justifies the need to develop new clinical studies to test its effectiveness in humans. The next step is to investigate how it helps maintain homeostasis of the mitochondrial and endoplasmic reticulum, and, to a greater extent, whether melatonin therapy would allow delay or cessation of the progressive kidney damage by using chronic pharmacological use in kidney repair and – regeneration is promoted.
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More information:
Ahmad Agil et al., Melatonin Improves Mitochondrial Dynamics and Function in the Kidney of Zücker Diabetic Fat Rats, Journal of Clinical Medicine (2020). DOI: 10.3390 / jcm9092916
Samira Aouichat et al., Melatonin improves the IRE1α pathway mediated by endoplasmic reticulum stress in Zücker Diabetic Fatty Rat, Pharmaceuticals (2021). DOI: 10.3390 / ph14030232
Provided by the University of Granada
Quote: Melatonin has been shown to protect kidney damage caused by obesity in diabetes (May 27, 2021). Retrieved May 28, 2021 from https://medicalxpress.com/news/2021-05-melatonin-shown-kidney-obesity-diabetes.html
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