Effect of Lipopolysaccharide from Rhodobacter sphaeroides on Inflammatory Pathway and Oxidative Stress in Renal Ischemia/Reperfusion Injury in Male Rats.

Ischemia/reperfusion injury (IRI) is caused by a sudden temporary impairment of the blood flow to the particular organ. The IRI of the kidneys is one of the main causes of acute kidney injury. A vigorous inflammatory and oxidative stress response to hypoxia and reperfusion usually happens as IRI consequences that disturb the organ function. The current study aimed to investigate the effect of antagonizing toll-like receptors (TLRs) effects by lipopolysaccharide obtained from Rhodobacter sphaeroides (LPS-RS) on this critical condition. In total, 28 adult male Wistar rats were divided into four groups (n=7) as follows: the sham group which underwent only laparotomy; control group that underwent laparotomy and IRI induction; vehicle group which was similar to the control group plus vehicle treatment, LPS-RS group that was similar to the control group but was pretreated with 0.5 mg/kg of LPS-RS. The results of the current research showed that LPS-RS reduced interleukin-1ß, interleukin-6, tumor necrosis factor α, and 8-isoprostane levels, compared to the control IRI group. However, LPS-RS did not ameliorate the kidney injury as manifested by the elevated levels of urea, creatinine, and neutrophil gelatinase-associated lipocalin. Taken together, the present study demonstrated that LPS-RS at the tested dose failed to offer a renoprotective effect against the IRI in rats.

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 TLR4, 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 30 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 0.1 mg/kg of ULPS-RS), and ULPS-RSH (same as the control group, but pretreated with 0.2 mg/kg of ULPS-RS). Subsequent to 30 min of ischemia and 2 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 6, interleukin 1ß, and tumor necrosis factor α), oxidative stress marker (8-isoprostane), apoptosis mediators (B cell lymphoma 2 [Bcl2]), and Bcl2-associated X protein (Bax). In the control group, all of the measured parameters were significantly elevated in response to IRI, except for Bcl2, 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.