Effects of nitric oxide synthase inhibitor (L-NAME) on cytopathologic changes due to cholestasis in hepatic cells of adult male rats

Abstract

Obstructive cholestasis is associated with overproduction of endogenous opioids, nitric oxide (NO) and cytokines in the blood stream. Nitro-L-arginine methyl ester (L-NAME) administration decreases the NO serum level and it is able to reduce related complications. The aim of this research is to survey the effects of the NO inhibitor on complications relating to cholestasis in liver cells and intrahepatic biliary ducts. We used five groups of animals: control, sham-operated (surgical control), bile duct ligated (BDL) group, BDL and normal saline infused group, and BDL with L-NAME administrated group. After 3 weeks all animals were killed, histopathology of liver cells and intrahepatic biliary ducts were evaluated by hematoxylin-eosin (HE), PAS (periodic acid-Schiff) and trichrome staining. The status of inflammation and fibrosis was evaluated by the modified Knodell score system. Microscopic study of different groups showed that the necro-inflammatory score in the control group was 0.36, it was 1 in the sham-operated group and it raised to 15.2 in the cholestatic group. After administration of L-NAME it had a meaningful decrease to 7, but in the saline-treated group, the score was 16. L-NAME with the mentioned dose was capable of decreasing the serum nitric oxide level, although it is able to decrease the unfavorable complications of cholestatic jaundice.

Cardiovascular effects of high-fructose intake in rats with nitric oxide deficiency

“…( 2011 ) demonstrated that inducible NO synthase (iNOS) is involved in the onset of fructose-induced liver steatosis and that the key factor in this process is the increased formation of reactive oxygen species in hepatic tissue. In mice receiving high amounts of fructose (Spruss et al ., 2011 ) or in rats with cholestasis (Monsef, 2012 ), various parameters indicating the status of inflammation and fibrosis in liver were ameliorated after treatment with unspecific NO synthase inhibitors like L-NAME, or in iNOS knockout mice. This may partially elucidate our observation of the failure of fructose administration to induce abnormalities in liver and plasma parameters in NO deficient rats.…”