High-sulfated derivative of polysaccharide from Ulva pertusa improves Adriamycin-induced nephrotic syndrome by suppressing oxidative stress

Nephrotic syndrome (NS) is characterized by proteinuria, hyperlipidemia, and hypoalbuminemia. Ulva pertusa, a green seaweed, is a nutritional supplement. In this study, the high-sulfated derivative of Ulva pertusa polysaccharide (HU) was prepared by combining U pertusa polysaccharide with chlorosulfonic acid. The NS rat model was established by tail vein single injection of Adriamycin (6.0 mg kg(-1)). Normal rats were used as the control group. NS rat models were treated with HU or U (173 mg kg(-1) day(-1)). After treatment for 6 weeks, we assessed urine protein, renal function, and blood lipids, and observed mor-phology and histologic injury of the kidney and glomerular microstructure. Furthermore, we detected antioxidant enzyme activity and expression level of the Keap1/Nrf2 signaling pathway to explore the potential mechanism of HU. Results showed that HU not only alleviated hyperlipidemia and hypoalbumi-nemia, but also reduced urine protein by inhibiting podocyte detachment, thickening of the glomerular basement membrane, and expression of kidney fibrosis markers (collagens I and IV). In addition, HU enhanced antioxidant enzyme activity (GSH-Px, CAT, SOD) in both serum and the kidney, which may be due to upregulating the expression of Nrf2 and downregulating the expression of Keap1. In conclusion, HU appears to be effective in attenuating NS in rats through suppressing oxidative stress by regulating the Keap1/Nrf2 signaling pathway.