Potential involvement of PPAR α activation in diminishing the hepatoprotective effect of fenofibrate in NAFLD: Accuracy of non- invasive panel in determining the stage of liver fibrosis in rats.

BACKGROUND: Although Fenofibrate (FF) is a hypolipedmic drug and one of the PPARα agonists which is a drug target for non alcoholic liver disease (NAFLD), no studies had investigated its potential hepatic effects in such cases.

AIM: To compare between the effect of FF and Gemfibrozil (GF) on the prognosis of NAFLD in rats.

METHODS: Sixty four rats were used and classified into two main groups. Group I (treated for 6 weeks): naïve, FF, GF groups and Group II (treated for 14 weeks and drugs were added at the last 6 weeks): Control, high fat diet (HFD) untreated, HFD+FF, HFD+FF+folic acid (FA) and HFD+GF groups. Body weight (BW), liver index (LI), renal perfusion test (RPT), glomerular filtration rate (GFR), serum creatinine (S.cr), plasma homocysteine (Hcy), liver function, non invasive markers of fibrosis and histopathology were done.

RESULTS: HFD produced significant increase (P<0.05) in BW, LI, S.cr, plasma Hcy, lipid profile and liver enzymes. It showed significant (P<0.05) decrease in GFR and RPT. These findings were correlated to the histopathology. FF through its effect on GFR and renal function induced significant increase in plasma Hcy and that decreased its effectiveness in managing NAFLD associated with hyperlipidemia. The addition of FA improved significantly its hypolipidemic and hepatotoxic effects.GF showed none of the above FF effects and this may be due to its low affinity to PPAR α.

CONCLUSIONS: There is preference of adding FA to FF or using GF instead in cases of NAFLD. Moreover, this work implies the enhanced liver fibrosis (ELF) panel diagnostic performance in diagnosis of any and moderate degree of fibrosis in rats with NAFLD.