US EPA

1646370 

Journal Article 

Role of Heme Oxygenase-1 Induction and Type 5 Phosphodiesterase Inhibition in Hepatic Ischemia Reperfusion Injury in Male Albino Rats 

Eissa, HM; Saleh, ME; Elsayed, LA; Hassan, HA 

2012 

1 

Life Science Journal
ISSN: 1097-8135 

9 

3 

1711-1724 

WOS:000315724100248 

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 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), a 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 following ischemia, 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 change (p >0.05) in total hepatic nitrite content compared to group II. 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 group II. 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) increasd. 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 < 0.05) increased.



Conclusion: Induction of HO-1 gene expression and inhibition of phosphodiesterase type 5 could have synergistic hepatoprotective effects against I/R injury. Further investigations are recommended for using agents that are not hepatotoxic and can protect the liver and other organs from I/R injury. [Hassan M. Eissa; Mohammad E. Saleh; Laila A. Elsayed; and Hend A. Hassan. Role of Heme Oxygenase -1 Induction and Type 5 Phosphodiesterase Inhibition in Hepatic Ischemia Reperfusion Injury in Male Albino Rats. Life Sci J 2012;9(3):1711-1724] (ISSN:1097-8135). http://www.lifesciencesite.com. 250 

Hepatic ischemic-reperfusion injury; Heme Oxygenase-1; Nitric oxide; Phosphodiesterase Type 5 Inhibition