Effect of some calcium channel blockers [nifedipine and amlodipine] on the injury associated to hepatic ischemiareperfusion in albino rats

ABSTRACT

Hepatic ischemia is an important factor in the development of hepatic degeneration and necrosis in different hepatic pathological conditions. This study was conducted to declare the effect of pretreatment of albino rats with dihydropyridine L-type calcium channel blockers [nifedipine and amlodipine] on hepatic ischemia reperfusion [l/R]. Furthermore this study investigated the effect oi IIR on plasma levels of endothelin-1 [ET-1] and nitric oxide [NO] and their pathophysiologic links to maintenance of hepatic function. This study was carried on 36 male albino rats. The animals were divide into 6 equal groups, each consisted of 6 rats. Group [1] sham operated [rats subjected to anesthesia and laparotomy]. Group [II] control l/R rats, pre-treated with saline. Group [ill] treated with nifedipine [2mg/kg/day] intré-gasttic for 6 weeks before exposure to sham operation. Group [IV] l/R treated with nitedipine with the same previously mentioned dose and for the same duration before induction of VR. Group [V] amlodipine pretreated [0.5mg/kg/day] for 6 weeks, intragastrically and then exposed to sham operation. Group [VI] received amlodipine 0.5mg/kg/day for 6 weeks before being subjected to I/R. Transient hepatic ischemia for 90 minutes was done under anesthesia by hepatic vascular pedicle clamping followed by 30 minutes reperfusion. Hepatic cell function was tested by measuring plasma alanine transferase [ALT]. This Is In addition to measurements of hepatic tissue calcium content, plasma endothelin-l and plasma nitrites. It was found that UR produced a significant increase in plasma ALT. ET-1, nitrites and hepatic tissue calcium. Both nifedipine and amlodipine induced hepato-protective effect confirmed by prevention of the elevation in plasma levels of ALT and hepatic tissue calcium load. Each of nifedipine and amlodipine had equally prevented the hepatic accumulation of calcium. In spite of this equieffective protection any of the drugs exerted significant changes in plasma ET-1 levels. While plasma nitrites levels remained high. Further studies of these results on hepatic patients are recommended especially in patients given nifedipine or amlodipine for associated cardiovascular problems