Melatonin was proven to guard kidney harm attributable to weight problems with diabetes

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University of Granada

An international study conducted by UGR shows the effectiveness of this treatment in slowing, delaying and / or preventing the progression of kidney disease towards kidney failure in animal models of diabetes (obesity and type 2 diabetes).

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 and type -2 diabetes) and its complications.

In particular, in two new studies recently published in the prestigious scientific journals “Journal of Clinical Medicine” and “Pharmaceuticals”, researchers developed it in an obese and diabetic rodent model and demonstrated that melatonin protects the kidney damage caused by 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 the 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), which leads to the loss of kidney functionality. as a preliminary step in the development of kidney failure and the need for hemodialysis or transplant.

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 at the UGR’s Department of Pharmacology, explains: “Kidney damage is caused by metabolic complications of obesity such as diabetes, high blood pressure, blood lipid disorders, or fatty liver disease. Given that the prevalence of these pathologies (collectively recognized as metabolic syndrome) continues to increase, kidney damage and its progression to kidney failure over time has become a health problem affecting millions of people worldwide, with high socio-economic costs requiring hemodialysis facilities and / or kidney transplant services with the appropriate compatibility studies required ”.

The importance of the work lies not only in the effectiveness of melatonin in counteracting the two proposed mechanisms of kidney damage (based on the one hand on the change in mitochondrial function and dynamics and on the other hand on the function of the endoplasmic reticulum (on the other hand)). ER)), but they also suggest an alternative preventive treatment that would improve this kidney function with a well-studied drug with a very high safety profile like melatonin, a drug that has to be prescribed by a doctor in the EU and is already at the Administered treatment for 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 greatest challenge is the application of melatonin and other strategies such as intermittent fasting in medicine, particularly to examine the possibility of a treatment perspective for the above-mentioned pathologies (diabetes and its complications), which include mitochondrial damage and an increase in oxidative stress associated meta-inflammation (inflammation of metabolic origin) ”, emphasizes Agil.

According to the results reported by these researchers, melatonin could help treat kidney damage, which justifies the need to develop new clinical studies to test its effectiveness in humans. The encouraging results achieved in preclinical models invite melatonin to be moved to the next phase to investigate how it helps in maintaining homeostasis of the mitochondrial and endoplasmic reticulum, and to a greater extent if melatonin therapy is one Delay or stop the progressive kidney damage by promoting its chronic pharmacological use in kidney repair and regeneration.

This study was funded by the Ministry of Science and Innovation (Spain) project SAF2016-79794-R and the European Regional Development Fund (ERDF) led by Professor Ahmad Agil.

Currently, the UGR research group that developed this work is interested in working with pharmaceutical companies that want to help market a patent. This team is also conducting further experiments with another molecule that acts as a melatonin agonist.

This research was carried out by a multidisciplinary team of researchers from the Department of Pharmacology of the UGR (Faculty of Medicine), the Institute of Neuroscience of the University of Granada and the 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 (Department of Endocrinology and Nutrition, Universitario La Paz Hospital, Madrid) and Ressul Reiter from the Institute of Structural Biology (University of Texas, San Antonio, USA).

Bibliography:

1.- Agil A, Chayah M, Visiedo L, Navarro-Alarcó M, Rodriguez Ferrer JM, Reiter JR, Fernández-Vázquez G. 2020. Melatonin improves mitochondrial dynamics and functions in the kidney of sugar-diabetic fat rats. J Clinical 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 the IRE1α pathway mediated by endoplasmic reticulum stress in Zücker diabetic fat rats.Pharmaceuticals.2021. 8; 14 (3): 232. doi: 10.3390 / ph14030232.

Pictures in the attachment:

Microscopic photographs show the abnormal appearance of the kidneys (with kidney damage) in obese and diabetic rats without melatonin treatment (left panel) and, on the right, the improvement in kidney damage in rats treated with melatonin (right panel).DR. Ahmad Agil |

Get in touch.

Dr. Ahmad Agil, head of the research team and member of the: Institute of Neuroscience-UGR, the Biosanitary Institute of Granada and.

Department of Pharmacology, University of Granada.

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