Renoprotective Potential of the Ultra-Pure Lipopolysaccharide from Rhodobacter Sphaeroides on Acutely Injured Kidneys in an Animal Model

One of the main causes of acute kidney injury is ischemic reperfusion injury (IRI). Inflammatory response, apoptotic damages, and oxidative stress-related injuries are all involved in the pathogenesis of IRI. Toll-like receptors (TLR) are strongly associated with IRIs, especially TLR۴, which is markedly induced in response to IRI. Accordingly, the current study aimed to investigate the potential renoprotective effect of ultrapure lipopolysaccharide from Rhodobacter sphaeroides (ULPS-RS) at two doses in an animal model of bilateral IRI. A total of ۳۰ adult male rats were divided randomly into five equal groups of control (laparotomy plus bilateral renal IRI), vehicle (same as the control group, but pretreated with the vehicle), sham (laparotomy only), ULPS-RS (same as the control group, but pretreated with ۰.۱ mg/kg of ULPS-RS), and ULPS-RSH (same as the control group, but pretreated with ۰.۲ mg/kg of ULPS-RS). Subsequent to ۳۰ min of ischemia and ۲ h of reperfusion, serum samples were collected for measuring urea, creatinine, and neutrophil gelatinase-associated lipocalin. Afterward, tissue samples were obtained from all animals to measure inflammatory mediators (interleukin ۶, interleukin ۱β, and tumor necrosis factor α), oxidative stress marker (۸-isoprostane), apoptosis mediators (B cell lymphoma ۲ [Bcl۲]), and Bcl۲-associated X protein (Bax). In the control group, all of the measured parameters were significantly elevated in response to IRI, except for Bcl۲, which decreased significantly. On the other hand, exactly opposite effects were observed in the ULPS-RS treated groups indicating the nephroprotective effect of this compound against IRI at both tested doses. The findings reveal for the first time that ULPS-RS has the therapeutic potential of attenuating the renal dysfunction induced by IRI.

Keywords:

Bax , Bcl۲ , F۲-Isoprostane , IL-۱β , Il۶ , Ischemic reperfusion injury , Ngal , pure TLR۴ antagonist , Tnfα