Gelatin Hydrolysate from Bigeye Snapper (Priacanthus tayenus) Skin Attenuates the Progression of Diabetic Nephropathy in Rats by Modulating Oxidative Stress, Inflammatory Responses, and Endoplasmic Reticulum Stress Signaling Pathways.

Diabetic nephropathy (DN) is a major complication of chronic hyperglycemia. Although fish gelatin hydrolysate has antioxidant, anti-inflammatory, and antihypertensive properties, its renoprotective effects in DN remain unclear. This study investigated its effects on renal oxidative stress, inflammation, fibrosis, and endoplasmic reticulum (ER) stress in diabetic rats. Thirty male Wistar rats were fed a normal chow diet or a high-fat diet for 4 weeks. Diabetes was induced in high-fat-diet-fed rats by a single intraperitoneal injection of streptozotocin (30 mg/kg). Diabetic rats were randomly assigned to receive no treatment (untreated diabetes), gelatin hydrolysate at 250 or 500 mg/day, or metformin at 100 mg/kg/day groups (n = 6/group), while normal-chow-fed rats served as controls. Treatments were orally administered for 8 weeks. High-dose gelatin hydrolysate improved metabolic disturbances and renal dysfunction, whereas low-dose gelatin hydrolysate and metformin more effectively reduced oxidative stress, as indicated by decreased 8-OHdG expression. All treatments reduced renal injury, fibrosis, and inflammatory markers. ER stress-related proteins were also attenuated, with the greatest changes observed in IRE1/XBP1-associated markers. These findings provide in vivo evidence that GLH treatment is associated with improved renal outcomes and reduced markers of oxidative stress, inflammation, fibrosis, and ER stress in DM rats.