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This study aimed to investigate if C21 could prevent acute renal injury induced by sepsis by regulating the expression of p-AKT/PI3K. Five equal groups of 25 adult male Swiss-albino mice were randomly divided (n=5): sham (laparotomy without CLP), CLP, vehicle (equivalent amount of DMSO one hour before CLP), and C21 (0.03 mg/kg, one hour before CLP). ELISA was used to measure serum inflammatory mediators, and the expression of PI3K and P-AKT was determined using PCR and immunohistochemistry (IHC), respectively. TNF, TNF receptor, F8-isoprostane, urea, creatinine, and IL-6 blood levels were considerably lower in the CLP group (p<0.05) compared to the sham group, whereas the C21 treated group had significantly (p<0.05) greater levels of these inflammatory mediators. The IHC analysis revealed that P-AKT expression was significantly lower (p<0.05) in the CLP group compared to the sham group, while the C21 pretreatment group had significantly higher levels of P-AKT expression compared to the CLP group (p<0.05). The PI3K expression in the CLP group was significantly lower than in the sham group (p<0.05), according to PCR results, whereas the PI3K expression in the C21 pretreatment group was significantly greater than in the CLP group (p<0.05). This study showed that C21 might reduce levels of pro-inflammatory cytokines, including TNF-, IL-6, and TNF receptor, by modulating the PI3K/AKT signaling pathways, which can, in turn, reduce renal dysfunction during CLP-induced sepsis in male mice.

No abstract

Renal ischemia-reperfusion (Renal I/R) leads to acute kidney injury (AKI),a major kidney disease associated with an increasing prevalence and high mortality rates. A variety of experimental models,both in vitro and in vivo,have been used to study the pathogenic mechanisms of ischemic AKI and to test reno-protective strategies. Aim: To study potential protective effects of artesunate on renal I/R injury. Renal I/R injury was unilaterally induced in adult (3 to 5 months) male Sprague-Dawely rats,whose weights ranged from 180 to 390 g. Thereafter,the animals were pre-treated with artesunate intra-peritoneally,and at the end of reperfusion sacrificed humanely. Plasma,serum and tissue samples were obtained for analysis. Plasma concentrations of NGAL (neutrophil gelatinase associated lipocalin),an iron-trafficking protein involved in multiple processes such as apoptosis,innate immunity and renal development,and tissue concentrations of IL-18 (Interleukin-18) were measured via ELISA analysis. Serum urea and creatinine were also measured in the samples. Artesunate improved renal ischemia reperfusion,including renal function and brought about reductions in inflammatory mediators and kidney tissue injury. Plasma concentrations of NGAL and tissue concentrations of IL-18 were significantly (p < 0.05) lower in the artesunatepretreated group than in the vehicle and control groups. Furthermore,serum concentrations of urea and creatinine were significantly (p < 0.05) decreased in the pretreated group as compared to the control group. Artesunate can significantly improve renal function following I/R through down-regulation of inflammatory parameters and NGAL expression. Furthermore,it could serve as a potential therapy in ischemia reperfusion-induced acute kidney injury.

No abstract