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.

Cardioprotective effects of irbesartan in polymicrobial sepsis : The role of the p38MAPK/NF-κB signaling pathway.

BACKGROUND: Sepsis is a systemic inflammatory response usually correlated with multi-organ failure. Myocardial dysfunction is one of the adverse outcomes in septic patients and results in high mortality rates. The aim of this study was to investigate the impact of irbesartan in attenuation of cardiac depression during polymicrobial sepsis via decreased activation of the phospho-p38MAPK/nuclear factor (NF)-κB signaling pathway. MATERIALS AND METHODS: A model of polymicrobial sepsis induced via cecal ligation and puncture (CLP) with 8- to 12-week-old albino mice was used. Mice were treated with i.p. irbesartan (3 mg/kg) 1 h before CLP. Using a micro-tipped transducer catheter, the following hemodynamic parameters were evaluated after CLP: heart rate, ejection fraction, left ventricular (LV) end-diastolic pressure, LV systolic pressure, and cardiac output. Plasma levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, monocyte chemoattractant protein-1 (MCP-1), and cardiac troponin I (cTn-I), were measured via ELISA analysis. The degree of p38MAPK and NF-κB phosphorylation was assessed via Western blotting. RESULTS: Mice treated with irbesartan displayed improvement in LV function (ejection fraction: 42.4 ± 1.1% vs. 27.8 ± 3% in CLP mice). The attenuation of cardiac depression in irbesartan-treated mice was associated with lower levels of MCP-1 in plasma and a reduction in the levels of TNF-alpha, IL-1beta, and IL-6. Furthermore, irbesartan-treated mice displayed lower expression levels of p38-MAPK and NF-κB phosphorylation. CONCLUSION: Irbesartan can attenuate cardiac dysfunction during polymicrobial sepsis possibly via a reduction of proinflammatory cytokines through decreased activation of the p38MAPK/NF-κB pathways.