Melatonin attenuates renal fibrosis in diabetic mice by activating the AMPK/PGC1α signaling pathway and rescuing mitochondrial function

Abstract

Mitochondrial homeostasis is a highly regulated process that serves a critical role in the maintenance of renal structure and function. The growing interest in the field of mitochondrial homeostasis promises to provide more information regarding the mechanisms involved in diabetic renal fibrosis, and aid in the development of novel strategies to combat the disease. In the present study, the effects of melatonin on renal damage in mice with diabetes were evaluated and the underlying mechanisms were investigated.

Protective Effects of Melatonin Against Aristolochic Acid-Induced Nephropathy in Mice

“…Increased production of TGF-β and activation of Smad2/3 along with an elevated expression of α-SMA, a myofibroblast marker, and fibronectin after AA injection was also significantly attenuated by melatonin, suggesting that the hormone ameliorated AA-induced fibrotic processes mainly through suppression of TGF-β/Smad signaling pathway. In line with our findings, previous studies have reported that melatonin ameliorated cyclosporine A- [34], carbon tetrachloride- [35], unilateral ureteral obstruction- [36], 5/6 nephrectomy- [13], or diabetes [15]-induced renal fibrosis.…”

“…A previous study reported that administration of exogenous melatonin ameliorated renal injury and dysfunction in pinealectomized rats [5]. It has also been shown that melatonin displays protective effects in various types of acute kidney injury (AKI) [6][7][8][9][10][11] and chronic kidney disease (CKD) [12][13][14][15]. However, the effects of melatonin on AAN have not yet been investigated.…”

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

“…The ability of this hormone to reduce oxidative stress in renal mitochondria is in line to other reports in different tissues [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ] which also indicate the mitochondria as a therapeutic target for the antioxidant actions of this indolamine. In summary, melatonin therapy improves overall mitochondrial dysfunction and altered mitochondrial dynamics observed in the kidney of obese diabetic condition as others reported in other conditions in renal damage [ 66 , 67 ]. Our findings reinforce a statement made by others that melatonin supplementation could be useful for improvement in stable outpatient renal transplant recipients [ 68 ].…”

Melatonin Inhibits Transforming Growth Factor-β1-Induced Epithelial–Mesenchymal Transition in AML12 Hepatocytes

“…Bleomycin-induced experimental lung fibrosis was also attenuated by treatment with melatonin [27]. In addition, melatonin has been shown to attenuate kidney fibrosis induced by CCl4 [28], unilateral ureteral obstruction [29], or diabetes [30]. Interestingly, it was also reported that melatonin ameliorated liver fibrosis induced by CCl4 [12][13][14], thioacetamide [15], or high-fat diet [16].…”