NEPHROPROTECTIVE EFFECT OF OLMESARTAN ON RENAL ISCHEMIA REPERFUSION INJURY IN MALE RATS: THE ROLE OF NRF2/HO-1 SIGNALING PATHWAY.

OBJECTIVE: The aim: To investigate the Nephroprotective potential of Olmesartan in RIRI via modulation of the Nrf2/OH-1 signaling pathway. PATIENTS AND METHODS: Materials and methods: Thirty male rats were equally divided into four groups. The sham group was exposed to surgical conditions without induction of RIRI. The control group was exposed to ischemia by clamping the renal pedicles for 30 min, followed by 2h of blood restoration. The vehicle-treated group was received dimethyl sulfoxide (DMSO) by intraperitoneal injection (IP) 30 min before clamping. RESULTS: Results: Olmesartan-treated group was pretreated with Olmesartan a dose of 10 mg/kg IP; 30 min prior to induction of ischemia. Following 30 min of ischemia, the clamps were released and allowed to the reperfusion for 2 h. Blood samples were collected to examine the levels of serum urea and creatinine. Kidney tissue was used to measure the levels of cytokines (TNFα, IL6, MCP, BAX, BCL2 and isoprostane F2. Immunohistochemistry was used to assess the levels of Nrf2 and HO-1. Histological analyses were used to detect the tubular damage in the kidney. CONCLUSION: Conclusions: The results showed that Olmesartan alleviates renal tissue damage through activating the antioxidant effect mediated by Nrf2 signaling.

LUNG PROTECTIVE POTENTIAL EFFECT OF ZILEUTON DURING ENDOTOXAEMIA MODEL IN MALE MICE.

OBJECTIVE: The aim: This study was undertaken to investigatethe possible lung protective potential effect of zileuton during polymicrobial sepsis, through modulation of inflammatory and oxidative stress pathway. PATIENTS AND METHODS: Materials and methods: 24 adult male Swiss-albino mice aged 8-12 weeks, with a weight of 25-35g, were randomized into 4 equal groups n=6, sham (laparotomy without CLP), CLP (laparotomy with CLP), vehicle (equivalent volume of DMSO 1 hour prior to CLP), and Zileuton (5 mg/kg 1 hour prior to CLP) group. After 24 hrs. of sepsis, the lung tissue harvested and used to assess IL-6, IL-1B, IL-17, LTB-4,12(S) HETE and F2-isoprostane as well as histological examination. RESULTS: Results: Lung tissue inflammatory mediators IL-6, IL-1B, IL-17, LTB, 12 (S) HETE) and oxidative stress were carried out via ELISA. Lung tissue levels of IL-6, IL-1B, IL-17, LTB4, 12(S) HETE and oxidative stress (F2 isoprostan)level were significantly higher in sepsis group (p<0.05) as compared with sham group, while zileuton combination showed significant (p<0.05) lower level in these inflammatory mediators and oxidative stress as comparedto sepsis group. Histologically, All mice in sepsis group showed a significant (p<0.05) lung tissue injury, while in zileuton pretreated group showed significantly (p<0.05) reduced lung tissue injury. CONCLUSION: Conclusions: The results of the present study revealed that zileuton has the ability to attenuate lung dysfunction during CLP induced polymicrobial sepsis in male mice through their modulating effects on LTB4,12(S) HETE and oxidative stress downstream signaling pathways and subsequently decreased lungtissue levelsof proinflammatory cytokines (IL-1ß, and IL-6,IL-17).