Increased Sulfation in Gracilaria fisheri Sulfated Galactans Enhances Antioxidant and Antiurolithiatic Activities and Protects HK-2 Cell Death Induced by Sodium Oxalate.

Urolithiasis is a common urological disease characterized by the presence of a stone anywhere along the urinary tract. The major component of such stones is calcium oxalate, and reactive oxygen species act as an essential mediator of calcium oxalate crystallization. Previous studies have demonstrated the antioxidant and antiurolithiatic activities of sulfated polysaccharides. In this study, native sulfated galactans (N-SGs) with a molecular weight of 217.4 kDa from Gracilaria fisheri were modified to obtain lower molecular weight SG (L-SG) and also subjected to sulfation SG (S-SG). The in vitro antioxidant and antiurolithiatic activities of the modified substances and their ability to protect against sodium oxalate-induced renal tubular (HK-2) cell death were investigated. The results revealed that S-SG showed more pronounced antioxidant activities (DPPH and O2- scavenging activities) than those of other compounds. S-SG exhibited the highest antiurolithiatic activity in terms of nucleation and aggregation, as well as crystal morphology and size. Moreover, S-SG showed improved cell survival and increased anti-apoptotic BCL-2 protein in HK-2 cells treated with sodium oxalate. Our findings highlight the potential application of S-SG in the functional food and pharmaceutical industries.

Structural characterization, antioxidant activity, and protective effect against hydrogen peroxide-induced oxidative stress of chemically degraded Gracilaria fisheri sulfated galactans.

Sulfated polysaccharides (SPs) possess an extensive range of biological activities, such as the inhibition of oxidation, correlated with their molecular weight (MW) and chemical structure. In this study, we used the trifluoroacetic acid (TFA) controlled degradation method to degrade sulfated galactans (SG) isolated from Gracilaria fisheri and evaluated the antioxidant and protective effects of the low molecular weight SG (LMSG) against H2O2 on fibroblast cells for the first time. Degradation of native SG (NSG) with an initial MW of 217.45 kDa using different concentrations of TFA resulted in five degraded NSG with MW of 97.23, 62.26, 30.74, 2.63, and 2.59 kDa. The reduction in MW was positively correlated with TFA concentrations. Chemical structure analyses using FTIR and NMR indicated that the TFA degradation process did not significantly change the LMSG polysaccharide main chain but did change the functional groups. LMSG exhibited higher scavenging activities and enhanced the cellular activities of GSH, CAT, and SOD enzymes. Moreover, LMSG activated Nrf-2/ARE signaling and increased expression of antioxidant genes CAT and SOD, which corresponded to increased protective effects against H2O2-induced ROS generation in fibroblast cells. The study reveals modification of NSG by acid TFA degradation resulted in the creation of LMSG, which showed greater antioxidant activity.