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Article

Melatonin Improves Mitochondrial Dynamics and Function in the Kidney of Zücker Diabetic Fatty Rats

1
Department of Pharmacology and Neurosciences Institute, School of Medicine, University of Granada, 18016 Granada, Spain
2
Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospital of Granada, 18016 Granada, Spain
3
Department of Nutrition and Bromatology, School of Pharmacy, University of Granada, 18071 Granada, Spain
4
Department of Physiology, School of Medicine, University of Granada, 18016 Granada, Spain
5
Service of Microscopy, CIBM, University of Granada, 18016 Granada, Spain
6
Department of Cellular and Structural Biology, University of Texas Health Science at San Antonio, San Antonio, TX 78229, USA
7
Service of Endocrinology, La Paz Hospital, 28046 Madrid, Spain
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(9), 2916; https://doi.org/10.3390/jcm9092916
Received: 26 August 2020 / Revised: 4 September 2020 / Accepted: 8 September 2020 / Published: 10 September 2020
(This article belongs to the Special Issue Facing the Future: New Perspectives in Diabetes and Kidney Disease)
Obesity and associated diabetes (diabesity) impair kidney mitochondrial dynamics by augmenting fission and diminishing fusion, which results in mitochondrial and renal dysfunction. Based on available evidence, the antioxidant activities of melatonin may improve impaired renal mitochondrial function in obese diabetic animals by restoring the imbalanced dynamics through inhibiting fission and promoting fusion. Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally treated either with melatonin (10 mg/kg BW/day) (M-ZDF and M-ZL) or vehicle (C-ZDF and C-ZL) for 17 weeks. Kidney function was evaluated by measurement of total urine volume, proteinuria, creatinine clearance, and assessment of kidney mitochondrial dynamics and function. C-ZDF exhibited impaired dynamics and function of kidney mitochondria in comparison to C-ZL. Melatonin improved nephropathy of ZDF rats and modulated their mitochondrial dynamics by reducing expression of Drp1 fission marker and increasing that of fusion markers, Mfn2 and Opa1. Furthermore, melatonin ameliorated mitochondrial dysfunction by increasing respiratory control index and electron transfer chain complex IV activity. In addition, it lowered mitochondrial oxidative status. Our findings show that melatonin supplementation improves nephropathy likely via modulation of the mitochondrial fission/fusion balance and function in ZDF rats. View Full-Text
Keywords: nephropathy; diabetes; obesity; melatonin; mitochondrial function/dynamic; fission/fusion; Drp1; Mfn2; Opa1; ZDF rats nephropathy; diabetes; obesity; melatonin; mitochondrial function/dynamic; fission/fusion; Drp1; Mfn2; Opa1; ZDF rats
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MDPI and ACS Style

Agil, A.; Chayah, M.; Visiedo, L.; Navarro-Alarcon, M.; Rodríguez Ferrer, J.M.; Tassi, M.; Reiter, R.J.; Fernández-Vázquez, G. Melatonin Improves Mitochondrial Dynamics and Function in the Kidney of Zücker Diabetic Fatty Rats. J. Clin. Med. 2020, 9, 2916. https://doi.org/10.3390/jcm9092916

AMA Style

Agil A, Chayah M, Visiedo L, Navarro-Alarcon M, Rodríguez Ferrer JM, Tassi M, Reiter RJ, Fernández-Vázquez G. Melatonin Improves Mitochondrial Dynamics and Function in the Kidney of Zücker Diabetic Fatty Rats. Journal of Clinical Medicine. 2020; 9(9):2916. https://doi.org/10.3390/jcm9092916

Chicago/Turabian Style

Agil, Ahmad, Meriem Chayah, Lucia Visiedo, Miguel Navarro-Alarcon, José M. Rodríguez Ferrer, Mohamed Tassi, Russel J. Reiter, and Gumersindo Fernández-Vázquez. 2020. "Melatonin Improves Mitochondrial Dynamics and Function in the Kidney of Zücker Diabetic Fatty Rats" Journal of Clinical Medicine 9, no. 9: 2916. https://doi.org/10.3390/jcm9092916

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