Author/Authors :
Aal-Aaboda, M. S Department of Pharmacology - Faculty of Pharmacy - University of Misan, Iraq , Abu Raghif, A. R Department of Pharmacology - Faculty of Medicine - Al-Nahrain University, Iraq , Hadi, N. R Department of Pharmacology and Therapeutics - Faculty of Medicine - University of Kufa, Iraq
Abstract :
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), ULPSRS
(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 1β, 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.
Keywords :
TNFα , Bax , Bcl2 , IL-1β , IL6 , F2-isoprostane , Ischemic reperfusion injury , NGAL , pure TLR4 antagonist