NEPHROPROTECTIVE EFFECT OF GAMMA-SECRETASE INHIBITOR ON SEPSIS- INDUCED RENAL INJURY IN MOUSE MODEL OF CLP.

OBJECTIVE: The aim: This study was set out to assess the potential protective impact of MK0752 (a gamma secretase inhibitor) on sepsis-induced renal injury through modulation of inflammatory and oxidative stress pathways. PATIENTS AND METHODS: Materials and methods: Twenty-four Swiss-albino mice aged between eight and twelve week and weighted twenty to thirty-seven grams were randomly allocated into four groups (n=6 in each group). Sham group (laparotomy without cecal ligation and puncture (CLP), sepsis group (laparotomy with CLP), vehicle-treated group (equivalent volume of DMSO before the CLP), MK0752 treated group (5 mg/kg) single daily dose for three days before the CLP. Blood samples were used to assess the serum levels of urea and creatinine. The kidneys were used to assess tissue levels of the TNF-α, IL-10, IL-6, TNFR1, VEGF, notch1, jagged1 and tissue damage by histopathological analysis. RESULTS: Results: The current study shows that pretreatment with MK0752 ameliorates the renal damage by significantly reducing the proinflammatory cytokines and notch1 signaling. CONCLUSION: Conclusions: Taken together, these results suggest that MK0752 could be protective against the renal injury induced by sepsis through its ameliorative impact on renal architecture and modulating cytokines and Notch1 singling pathway. Further studies regarding the role of Notch signaling pathways would be worthwhile.

NEPHROPROTECTIVE EFFECTS OF CURCUMIN AGAINST CYCLOSPORINE A-INDUCED NEPHROTOXICITY IN RAT MODEL.

OBJECTIVE: The aim: The current study was designed to examine the possible Nephroprotective effects of CMN in preventing nephrotoxicity and oxidative stress caused by chronic administration of CsA in rats. PATIENTS AND METHODS: Materials and methods: This study consisted of four groups and each group was made up of 8 rats. The first group was considered as a control group (received vehicle (0.9%N/S orally, and olive oil S.C), and the rest included the following: CMN group (received CMN in a dose of 30mg/kg/day orally), CsA group (received CsA in a dose of 20mg/kg/day S.C), and CMN plus CsA combination group (received CMN (30mg/kg/day, orally) plus CsA (20mg/kg/day, S.C) for 21days). For each group, the following variables wereassessed: Serum urea concentration, Serum creatinine concentration, initial body weight, final body weight, Tissue MDA level, Tissue GpX1 level, Tissue CAT level, Tissue SOD level, and tissue IL-2 level, and histopathological examination. RESULTS: Results: Mean levels of serum urea and creatinine, tissue MDA, tissue IL-2, and histopathological scores are significantly (P<0.05) increased in the CsA group compared with the control, and CMN groups (normal renal tissue). Tissue SOD, CAT, and GpX1 activities are significantly (P<0.05) decreased in the CsA group compared with the control, and CMN group. Concomitant administration of CMN with CsA resulted in significantly (P<0.05) lower elevated levels of MDA, serum urea, and creatinine, significantly higher levels of antioxidant enzymes, and normalization of the altered renal morphology compared with CsA treated rats. CONCLUSION: Conclusions: CMN has antioxidant and anti-inflammatory properties that protect the kidney from CsA's toxicity.

Sitagliptin ameliorates the progression of atherosclerosis via down regulation of the inflammatory and oxidative pathways.

BACK GROUND: Atherosclerosis is the major cause of death. The most common risk factors are hyperlipidemia, diabetes, and other factors like chronic infection and inflammation. OBJECTIVE: This study was undertaken to assess the effect of sitagliptin on atherosclerosis via interfering with inflammatory and oxidative pathways. MATERIALS AND METHODS: A total of 18 local domestic male rabbits were included in this study. The animals were randomly divided into three groups (6 rabbits in each group): Group I normal were fed with chow (oxiod) diet for 12 weeks. Group II were fed with 1% cholesterol enriched diet for 12 weeks. Group III rabbits fed with cholesterol enriched diet for 6 weeks, and then continued on cholesterol enriched diet and treated with sitagliptin 125 mg/kg/day orally for the next 6 weeks. Blood samples were collected at the start of the study, at 6 weeks of the study and then at the end of treatment to measure serum lipids profile, hsCRP and TNFα. At end of the study, the aorta was removed for measurement of MDA, glutathione and, aortic intima-media thickness. RESULTS: Sitagliptin results in a significant reduction (p < 0.05) in serum level of total cholesterol (TC), triglycerides (TG), high sensitive C-reactive protein (hsCRP) and TNFα with a significant increase (p < 0.05) in serum HDL level. There was a significant reduction (p < 0.05) in aortic MDA, in comparison to the untreated control group. Furthermore, sitagliptin causes significant increment (p < 0.05) in aortic GSH in comparison to induced untreated group. Regarding histopathological results, sitagliptin results in a significant reduction (p < 0.05) in atherosclerotic lesions in comparison to the induced untreated group and significant reduction in aortic intima-media thickness (p < 0.05). CONCLUSION: Sitagliptin reduced atherosclerosis progression in hyperlipidemic rabbit via its effect on lipid parameters and interfering with inflammatory and oxidative stress.