Antidiabetic and Nephroprotective Effects of Polysaccharide Extract from the Seaweed Caulerpa racemosa in High Fructose-Streptozotocin Induced Diabetic Nephropathy

BACKGROUND: Nephropathy is a frontline complication of diabetes mellitus (DM) associated with impaired redox-inflammatory networks. The study investigated the antidiabetic and nephroprotective potentials of PCR against diabetic nephropathy (DN) in rats. METHODS: DN was induced in rats using a combination of a high fructose solution for 4 weeks and an intraperitoneal injection of streptozotocin (35 mg/kg). Diabetic rats were treated with PCR (100 and 400 mg/kg body weight) for 8 weeks. Serum biochemical parameters as well as renal oxidative stress parameters, proinflammatory cytokines, Western blot and histopathological analyses were evaluated. RESULTS: There were significant increases in fasting blood glucose, urinary albumin, serum creatinine, blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL-C) levels in diabetic rats compared to the non-diabetic control rats. DM-induced DN prominently depressed renal superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, whereas renal malondialdehyde (MDA) level was markedly increased. Furthermore, renal inflammatory cytokines, IL-1β, IL-6, TNF-α and TGF-β, were considerably elevated compared to non-diabetic control rats. Additionally, DN rats showed a significant increase in renal fibrosis, as evidenced by increased expression of TGF-β1, collagen-1, fibronectin and alpha-smooth muscle actin (α-SMA) in the kidneys. Histopathological lesions were consistent with tubule thickening and glomerular hypertrophy. Conversely, PCR treatment exerted significant attenuation of hyperglycemia, dyslipidemia and renal oxidative stress indicators. The increased renal levels of IL-1β, IL-6, TNF-α and TGF-β were also notably reversed dose-dependently with alleviation of nephropathic histology. Furthermore, PCR reduced the expression of α-SMA, fibronectin, collagen-1 and TGF-β1 in the renal tissues. CONCLUSION: Our results suggest that PCR displayed antidiabetic and nephroprotective effects against DN by impeding oxidative stress and inflammation. As such, PCR has potentials as a food supplement for alleviating renal dysfunction caused by diabetes.