Rebamipide ameliorates hepatic dysfunction induced by ischemia/reperfusion in rats

Area of Science:

• Hepatology
• Biochemistry
• Pharmacology

Background:

• Hepatic ischemia/reperfusion (I/R) injury is a significant clinical challenge.
• Lipid peroxidation is implicated in I/R-induced liver damage.
• The impact of I/R on hepatic secretory and microsomal functions requires further elucidation.

Purpose of the Study:

• To investigate the relationship between lipid peroxidation and hepatic secretory/microsomal dysfunction during I/R.
• To evaluate the protective effects of free radical scavengers against I/R-induced liver injury.

Main Methods:

• Rats were subjected to 60 minutes of hepatic ischemia followed by 1 and 5 hours of reperfusion.
• Animals were pretreated with free radical scavengers: rebamipide, alpha-tocopherol, and allopurinol.
• Measurements included serum aminotransferase levels, microsomal lipid peroxidation, bile flow, cholate output, and microsomal enzyme activities (NADPH-cytochrome P450 reductase, aminopyrine N-demethylase, aniline p-hydroxylase).

Main Results:

• Ischemia/reperfusion significantly increased serum aminotransferase levels and microsomal lipid peroxidation.
• These increases were attenuated by rebamipide, alpha-tocopherol, and allopurinol.
• Bile flow and cholate output decreased post-I/R but were restored by free radical scavengers, especially rebamipide.
• NADPH-cytochrome P450 reductase activity decreased with I/R, an effect prevented by rebamipide.
• Specific drug effects varied on cytochrome P450 content and other enzyme activities.

Conclusions:

• Ischemia/reperfusion impairs hepatic secretory and microsomal functions primarily through increased lipid peroxidation.
• Free radical scavengers, notably rebamipide, demonstrate significant protective effects against I/R-induced liver dysfunction.
• Rebamipide's free radical scavenging activity is key to ameliorating these detrimental changes in liver function.