L -Carnitine and Melatonin Reverse CCl4 Induced Liver Fibrosis In Rats (Histological and Histochemical Studies)

Abstract

Carbontetrachloride (CCl 4 ) is closely related chemically to chloroform and likewise in hepatic poisons. This study was designed to evaluate the effects of carbon tetrachloride on liver of male rats and the reversing effects of L-carnitine and melatonin on established liver fibrosis. A total of 72 adult male albino rats were used in this study. The animals were divided into six groups. Group (1) animals of the first group were kept as control andtreated with paraffin oil twice weekly for eight weeks. Group (2) rats of the second group were injected with CCl4 intraperitoneally at 0.15 ml per rats (diluted 1:1 in liquid paraffin) twice weekly for eight weeks to produced liver fibrosis. Group (3) following establishment with CCl 4 which induced liver fibrosis, the rats were treated with L-carnitine at a dose level of 50 mg/kg for four weeks. Group (4) rats with liver fibrosis were injected intraperitoneally with melatonin at dose level of 10 mg/kg for four weeks. The fifth and sixth groups were given L-carnitine and/or melatonin at dose levels of 50 mg/kg and 10 mg/kg respectively for four weeks.Histological changes in the liver of rats treated with CCl 4 including liver fibrosis, architecture distortion and appearance of many pseudolobule. The fibrous tissues run in septa between the nodules. The liver damage varied from one area to another and varied from moderate fibrosis to cirrhosis.Quantitative measurement of the severity of liver fibrosis (area damage) was achieved by using computerized image analysis (Leica image) showed that highly significant increase in area of fibrosis was recorded in the case of rats treated with CCl 4 only.Quantitative DNA image analysis showed that 3% of aneuploid cells could be noticed in liver of rats treated with CCl 4 only. Histochemical results of rats treated with CCl 4 showed highly significant increase in grey level of mucopolysaccharides and protein levels. No histological and histochemical changes could be noticed in the liver of rats treated with either Lcarnitine or melatonin only. Both L-carnitine and melatonin were found to reverse CCl 4 induced liver damage.