, "Role of Heme Oxygenase -1 Induction and Type 5 Phosphodiesterase Inhibition in Hepatic Ischemia Reperfusion Injury in Male Albino Rats", Journal of American Science, vol. 8, issue -, pp. 1-15, 2012. Abstract

Abstract: Objective: Ischemia and reperfusion (I/R) injury is a pathophysiologic process whereby hypoxic organ damage is accentuated following return of blood flow and oxygen delivery to the compromised tissue. Both heme oxygenase producing carbon monoxide and nitric oxide synthase producing nitric oxide are involved in cytoprotection against ischemia and reperfusion. The aim of the present study was to investigate the possible hepatic cytoprotective effects of the pretreatment with cobalt (III) protoporphyrin IX chloride (Copp) and sildenafil citrate during ischemia, separately and in combination on hepatic I/R injury assessed by serum alanine transaminase (ALT), an established marker of hepatic IR injury, and necrotic index. Materials and methods: the study was carried out using fifty male albino rats belonging to the local strain aged eight weeks with body weight 165 to 200 gm. Rat were divided randomly into five groups, each included 10 rats: group I( control sham-operated), group II(hepatic I/R, ischemia for 45 minutes followed by reperfusion for 2 hours), group III(Copp pretreatment and I/R), group IV (I/R with sildenafil injection during ischemia), and group V(Copp pretreatment and sildenafil injection during ischemia). After two hours of reperfusion, animals were killed and blood is collected for serum ALT determination and hepatic tissues were used for determining histological evidence of hepatocellular injury assessed by necrotic index. Liver samples are also used for determining HO-1 gene expression and total hepatic nitrite content. Results: Hepatic ischemia and reperfusion (group II) resulted in hepatocellular injury as revealed by significant increases (p< 0.05) in mean value of serum levels of ALT and necrotic index. This was accompanied by significant (p < 0.05) increases in the mean values of hepatic HO-1 gene expression and total hepatic nitrite content compared to the control group. Induction of HO-1, by pretreatment of rats with Copp (group III) resulted in hepatocellular protection as evident by significant decreases (p < 0.05) in mean values of serum level of ALT and necrotic index. This was accompanied by significant increases in the mean values of hepatic HO-1 gene expression and )insignificant chang in total hepatic nitrite content compared to I/R group. Sildenafil citrate injection during ischemia (group IV) also resulted in hepatocellular protection as evident by significant decreases (p < 0.05) in mean values of serum levels of ALT and necrotic index accompanied by significant increases (p < 0.05) in the mean values of hepatic HO-1 gene expression and total hepatic nitrite content compared to I/R group. Compared to group III, sildenafil injection during ischemia produced insignificant changes (p > 0.05) in the mean value of serum level of ALT and necrotic index. However, HO-1 gene expressions was significantly (p < 0.05) decreased while total nitrite content was significantly (p < 0.05) increased. Compared to group II pretreatment of rats with Copp and Sildenafil injection during ischemia(group V) produced significant decreases (p < 0.05) in the mean value of serum levels of ALT, necrotic index while hepatic HO-1 gene expression and total nitrite content were significantly(p < 0.05) increase. Compared to group III and IV by pretreatment of rats with Copp and Sildenafil injection during ischemia produced significant decreases (p < 0.05) in the mean value of serum levels of ALT and necrotic index while hepatic HO-1 gene expression and total nitrite content were significantly(p p < 0.05) increased.
Conclusion: Induction of HO-1 gene expression and inhibition of phosphodiesterase type 5 could have synergistic hepatoprotective effect against I/R injury observed in many clinical situations. Further investigations are recommended for using agents that are not hepatotoxic and can protect the liver and other organs from I/R injury.

A, K., Y. SM, A. H, K. AE, and S. N, "Effects of ghrelin on sepsis induced acute kidney injury: one step forward", Clin Exp Nephrol , vol. 8, 2014. Abstract

Abstract
BACKGROUND:
Among the several disorders induced by sepsis, acute kidney injury (AKI) represents the most important economic burden problem that is associated with high mortality and morbidity rates. The aim of this study was to investigate the anti-inflammatory effects of ghrelin in sepsis-induced AKI and the possible role of vagus nerve.
METHODS:
Five groups were included: sham, cecal ligation and puncture (CLP), CLP-ghrelin, CLP-vagotomy and CLP-vagotomy-ghrelin group.
RESULTS:
Ghrelin treatment immediately after induction of CLP, significantly improved renal Glomerular filtration rate (GFR), serum creatinine, BUN and renal necrosis score as compared to the unprotected CLP group. In addition, ghrelin significantly decreased renal TNF alpha (111.5 ± 10.35 vs. 291.8 ± 15.8 pg/mg ptn), VCAM1 (6.28 ± 1.7 vs. 12.9 ± 1.2 µ/g ptn) and MPO (0.95 ± 0.13 vs. 2.5 ± 0.4 µ/g ptn) without significant increase in renal IL-10. Those effects were abolished by vagotomy.
CONCLUSION:
We concluded that ghrelin could represent new therapeutic window in early treatment of sepsis-induced AKI and this could be mainly due to its anti-inflammatory effects.

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