Melatonin Protects Against Diabetic Kidney Disease via the SIRT1/NLRP3 Signalling Pathway

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Melatonin, a hormone with anti-oxidative and anti-inflammatory properties, has demonstrated potential in mitigating diabetic complications; however, its specific effects and mechanisms in DKD remain unclear. This study aimed to investigate the protective effects of melatonin on podocyte injury and renal damage in DKD and to elucidate its underlying mechanisms.

In vitro, podocytes were exposed to high glucose (HG) and advanced glycation end products (AGEs) to simulate a diabetic environment. The effects of melatonin on podocyte viability, cytoskeletal organisation, oxidative stress markers (MDA, SOD, CAT, and GSH), and NLRP3 signalling activation were assessed. In vivo, a DKD mouse model was treated with melatonin, and renal function, histopathology, oxidative stress, and inflammation were evaluated. The role of SIRT1 in mediating the effects of melatonin was also investigated.

Melatonin improved podocyte viability, alleviated cytoskeletal disorganisation, reduced oxidative stress (decreased MDA, increased SOD, CAT, and GSH), and inhibited activation of the NLRP3 signalling pathway in podocytes and renal tissues. In DKD mice, melatonin reduced proteinuria, improved renal histopathology, and suppressed NLRP3-mediated inflammation. Mechanistically, melatonin upregulated SIRT1 expression, which inhibited NLRP3 activation and downstream inflammatory responses.

Melatonin protects against DKD by enhancing podocyte viability, reducing oxidative stress, and suppressing NLRP3-mediated inflammation through SIRT1 upregulation. These findings highlight the potential of melatonin as a therapeutic agent for DKD.