Show that melatonin protects against kidney damage caused by obesity with diabetes
An international study led by the UGR shows the efficacy of this treatment in slowing down, delaying and / or preventing the progression of kidney disease towards kidney failure in animal models of diabesity (obesity and its type 2 diabetes)
The research group of Neuropharmacology of pain of the ibs.GRANADA, scientists from the University of Granada (UGR), the La Paz University Hospital (Madrid) and the University of Texas (USA) have taken an important step in the fight against the damage kidney disease and its progression to kidney failure, which is closely related to diabesity (obesity and your type 2 diabetes) and its complications.
Specifically, in two new studies recently published in prestigious scientific journals "Journal of Clinical Medicine” and "Pharmaceuticals”, researchers have developed obese and diabetic rodents in a model, and have shown that melatonin protects kidney damage caused by diabesity.
Researchers have shown that chronic dosing of melatonin (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 damage ( nephrons), and their progression to renal failure.
Thus, it has been proven that melatonin prevents the impairment in the function and dynamics of cellular mitochondria, reducing the increase in the production of free oxygen radicals (responsible for oxidative stress). It also prevents the pathological alteration in the function of the endoplasmic reticulum (another cell cytoplasmic organelle), which under conditions of abnormally high oxidative stress is related to an increase in programmed cell death (the nephron) leading to the loss of kidney function, such as step prior to the development of kidney failure and the need for hemodialysis or transplantation.
The studies coordinated by the UGR show the efficacy of melatonin in stopping the progression of kidney damage mediated by mitochondrial damage and excess stress on the endoplasmic reticulum.
As explained by the main author of this study, the principal investigator of the Neuropharmacology of Pain research group at ibs.GRANADA and belonging to the Department of Pharmacology at the UGR Ahmad Agil, “kidney damage is caused by the metabolic complications of obesity, such as diabetes, hypertension, blood lipid disorders or fatty liver disease. Since the prevalence of these pathologies (as a whole recognized 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 around the world. the world, with a great socioeconomic cost, by requiring hemodialysis facilities and/or renal transplant services, with the corresponding necessary compatibility studies”.
Improve kidney function
The importance of the work lies not only in the effectiveness of melatonin to counteract the two proposed mechanisms of kidney damage, based on the one hand on the alteration of mitochondrial function and dynamics, and on the other on the function of the endoplasmic reticulum (ER)), but also propose an alternative preventive treatment . This would improve kidney function with a well-studied drug with a very high safety profile such as melatonin, which is a drug that in the EU 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 kidney damage to the nephron, manifested in decreased levels of creatinine clearance (the best marker of kidney function), proteinuria, and in the improvement of the renal structure, observed after the histopathological study of the kidney.
These results are in line with those previously published by these researchers in the last 10 years, which shows that the pharmacological administration of melatonin constitutes another new strategy in the therapeutic approach to diabesity (central obesity and its type 2 diabetes) 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 perspective of treatment of the aforementioned pathologies (diabesity and its complications) that imply an increase 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. The encouraging results obtained in preclinical models invite us to take melatonin to the next phase, in order to investigate how it helps to maintain mitochondrial homeostasis and the endoplasmic reticulum, and to a greater extent, whether melatonin therapy would allow to delay or stop progressive kidney damage, by promoting its chronic pharmacological use in the repair and regeneration of the kidney.
This study has been funded by the project SAF2016-79794-R of the Ministry of Science and Innovation (Spain), and the European Regional Development Fund (ERDF) led by Professor Ahmad Agil.
Currently, the UGR research group that has developed this work is interested in collaborating with pharmaceutical companies that wish to collaborate in the commercialization of a patent, a team that is also carrying out more tests with another molecule, which acts as melatonin agonist.
These research works have been carried out by a multidisciplinary team of researchers based in the Department of Pharmacology of the UGR (Faculty of Medicine), Institute of Neurosciences of the University of Granada, and Biosanitary Institute of Granada), under the direction of Ahmad Agil, in collaboration with Miguel Navarro (Department of Nutrition and Bromatology of the UGR); Gumersindo Fernández (Endocrinology and Nutrition Service of the La Paz University Hospital in Madrid) and Ressul Reiter, from the Department of Structural Biology (University of Texas, San Antonio, USA).
Bibliographic reference:
1.- Agil A, Chayah M, Visiedo L, Navarro-Alarcó M, Rodriguez Ferrer JM, Reiter JR, Fernández-Vázquez G. 2020. Melatonin improves the mitochondrial dynamics and functions in the kidney of Zuker diabetic fatty rats. JClinical Medicine. 2020. 10; 9 (9): 2916. doi: 10.3390 / jcm9092916.
2.-Aouichat S, Navarro-Alarcon M, Alarcón P, Salagre D, Ncir M, Zourgui L, Agil A. Melatonin Improves Endoplasmic Reticulum Stress-mediated IRE1? Pathway in Zücker Diabetic Fatty Rat.Pharmaceuticals.2021. 8;14(3):232. doi: 10.3390/ph14030232.