EFFECT OF SELECTED NATURAL PRODUCTS, THIOPROLINE AND PEGASYS® ON HEPATIC PLATELET ACTIVATING FACTOR (PAF) IN CCL4-INDUCED HEPATIC FIBROSIS IN RATS

This study aimed to estimate hepatic levels of platelet activating factor (PAF) in liver fibrosis induced by CCl4 in rats. A group of selected natural products; boswellic acids, curcumin and glycyrrhizin (preparation named OMNI® ; a drug under clinical trials for treatment of hepatitis C virus), Mirazid® (a commercially available schistomicidal drug), Thioproline (a commercially available hepatoprotective agent) and Pegasys® (peg interferon alpha-2a; a commercially available therapy for treatment of hepatitis C virus) were examined for their effect on hepatic PAF after CCl4 intoxication. For this purpose, 54 rats were used in the study. Rats were divided into 6 groups each comprised 9 rats. Group 1 was treated only with CCl4, groups 2 to 5 were treated with OMNI®, Mirazid®, Thioproline and Pegasys®, respectively, whereas the sixth group was the normal control group (with no treatment, except an injection of the vehicle). Liver damage was induced in all groups except normal control group (groups 1 to 5) by i.p. injection of 40% CCl4 in corn oil (0.375 ml/kg) 3 times a week for 3 weeks. One week after CCl4 intoxication, all tested drugs were injected i.p. daily for 3 weeks. Hepatic PAF concentration was estimated by HPTLC (high performance thin layer chromatography), while, levels of serum transaminases (ALT, AST), hepatic hydroxyproline (as markers of liver fibrosis), serum malondialdehyde and catalase (as markers of oxidative stress) were estimated spectrophotometrically. The hepatic PAF levels were significantly higher in CCl4 group (24.24±2.01 pmol equiv./mg) as compared to normal control (8.81±1.09 pmol equiv./mg) (p 0.001). Treatment with OMNI®, Mirazid®, Thioproline and Pegasys® reduced hepatic PAF significantly to be 11.84±0.22, 14.5±1.00, 13.17±0.54 and 14.26±1.09 pmol equiv./mg, respectively. This study may add further rational to the anti-fibrotic activity of the tested drugs via reduction of hepatic PAF.