The preventive effect of low molecular weight heparin on CCL₄-induced necrosis and apoptosis in rat liver.

BACKGROUND

Heparin having anti-inflammatory and anti-fibrotic properties may have therapeutic effect on liver injury. The present study investigated the effect of low molecular weight heparin (Enoxaparin) on carbon tetrachloride (CCl₄) induced hepatic necrosis and apoptosis in rats.

METHODS

Thirty male rats were divided into 5 groups. Group I: Control; Group II: Olive oil dissolved CCl₄ at dose of 1 mL/kg, ip, twice per week; Group III: CCl₄ and Enoxaparin at dose of 180 IU/kg, sc, daily; Group IV: Enoxaparin; Group V: Olive oil at dose of 1 mL, ip, twice per week. The liver histology at the forth week was examined by haematoxylin-eosin, Masson.s trichrome, Toluidine blue and Periodic acid schiff stains. Proliferative and apoptotic activities were assessed semi-quantitatively by proliferating cell nuclear antigen (PCNA) and caspase-3 immune staining and TUNEL method. Semi-quantitative values formulated by the equation HSCORE =ΣP(i) (i+1) including both distribution and intensity of staining. Additionally, nidogen and a-smooth muscle actin were labeled by immunohistochemistry.

RESULTS

CCl₄ group had marked hepatocelluar necrosis around the vena centralis and increased inflammatory cells and mast cells. Hepatocytes showed deposition of lipid droplets, decrease in glycogen, apoptosis, and picnotic or enlarged nuclei. Enoxaparin reduced necrosis, apoptosis, and number of mast cells but had no effect on lipid droplets in hepatocytes. HSCORE.s of caspase-3 and PCNA were also significantly decreased by administration.

CONCLUSIONS

Enoxaparin have beneficial effects against necrosis as well as apoptosis at the early stage of CCL₄ induced liver injury.