ABSTRACT
Liver fibrosis progresses to cirrhosis in several settings, for example, severe acute alcoholic hepatitis, and hepatitis C virus [HCV] reinfection after liver transplantation. Cirrhosis produces hepatocellular dysfunction, which is also a risk factor for hepatocellular carcinoma. We studied verapamil as a prophylactic, therapeutic antifibrotic drug alone and in combination with silymarin in experimental rat's liver-induced fibrosis. Liver fibrosis was induced by intra-peritoneal injection of rats with pig serum 0.5 ml twice weekly for 6 weeks, which resulted in score three fibrosis. Prophylactic verapamil alone and silymarin alone and a combination of both were administered at the same time of induction of liver fibrosis and continued for the duration of induction. Therapeutic verapamil was started on the last day of fibrosis induction and continued for 4 weeks. The extent of liver fibrosis was evaluated using Ishak's fibrosis score. Serum alanine aminotransferase [ALT] was measured for follow-up. Compared to fibrotic model rats, prophylactic verapamil, silymarin and combined verapamil plus silymarin significantly resulted in lower serum ALT levels. Prophylactic use of verapamil and silymarin each alone revealed score 2 fibrosis with positive alpha-SMA immunostaining; while prophylactic treatment with combined verapamil plus silymarin revealed no fibrosis supported by negative alpha-SMA immunostaining. Verapamil treated fibrotic rat's liver revealed significant regression in liver fibrosis scores with positive alpha-SMA immunostaining. Verapamil alone has a more significant prophylactic than therapeutic antifibrotic effect against induced liver fibrosis; it was more significant than silymarin. The combination of verapamil and silymarin, showed the best protection through their synergistic antifibrotic effect
ABSTRACT
In this study, L-arginine was administrated orally [p.o.] at a dosage of 10, 20 and 40 mg/kg of body weight, acutely once and chronically daily throughout two weeks prior to ulcer induction. Gastric mucosal lesion was induced by single oral administration of aspirin 300 mg/kg body weight suspected in water, after 36 hours fasting. The rats were killed within 24-48 hours and the gastrointestinal tract was subjected to gastric motility study and examined for the evidence of gross or microscopic change. The obtained results indicated the relaxant effect of L-arginine on gastric fundus and its protective role against the aspirin-induced ulcers in the rat