Melatonin Attenuates Contrast-Induced Nephropathy in Diabetic Rats: The Role of Interleukin-33 and Oxidative Stress

Abstract

Background. Inflammation and oxidative stress (OxS) contribute to the pathogenesis of diabetic kidney disease (DKD) and contrast-induced nephropathy (CIN). Patients with DKD were found to be more prone to CIN. Interleukin-33 (IL-33) is a proinflammatory cytokine, but its role in DKD and CIN is unknown. Methods. Thirty male Sprague-Dawley rats were enrolled. The first group was comprised of healthy rats (HRs), whereas the other four groups were made up of diabetic rats (DRs), diabetic rats with contrast-induced nephropathy (CIN + DRs), melatonin-treated diabetic rats (MTDRs), and melatonin-treated CIN + DRs (MTCIN + DRs). All groups except the HRs received 50 mg/kg/day streptozotocin (STZ). CIN + DRs were constituted by administrating 1.5 mg/kg of intravenous radiocontrast dye on the 35th day. MTDRs and MTCIN + DRs were given 20 mg/kg/day of intraperitoneal injection of melatonin (MT) from the 28th day for the constitutive seven days. Results. We observed increased IL-33 in the kidney tissue following induction of CIN in DRs. To determine whether MT is effective in preventing CIN, we administered MT in CIN + DRs and demonstrated that kidney tissue levels of OxS markers, inflammatory cytokines, and IL-33 were significantly diminished in MTCIN + DRs compared with other groups without MT treatment (p < 0.05). Conclusion. Inhibition of IL-33 with MT provides therapeutic potential in DKD with CIN.

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“…Melatonin elevates numerous antioxidant enzymes, such as SOD, peroxidase, GSH and lipid peroxidase [29]. Melatonin easily crosses cell membranes and leads to protection against free radical-induced damage to biomolecules [173].…”

“…Onk et al [173] found enhanced IL-33 levels in the kidney tissue following contrast-induced nephropathy (CIN) in diabetic rats; administration of melatonin in these animals considerably attenuated kidney tissue concentrations of inflammatory cytokines, oxidative stress biomarkers, and IL-33, indicating potential roles of melatonin in the treatment of diabetic nephropathy. Melatonin also reduced serum creatinine in rats with diabetic nephropathy.…”

Melatonin Attenuates Endothelial-to-Mesenchymal Transition of Glomerular Endothelial Cells via Regulating miR-497/ROCK in Diabetic Nephropathy

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