Modulalion of gene expression in the liver of mice 48-h post-treatment with CCl[4]

Carbon tetrachloride [CCl[4]] has been widely used to study mechanisms of hepatic injury and repair following toxic induced injury. This study was undertaken to evaluate the changes in gene expression in hepatocyte of injured liver of mice 48-h post-treatment with CCl[4]. Twelve adult male wild type mice were used in this experiment. The mice were fasted overnight and classified into two groups, [six mice each] the first group received in the following morning 4 ml/kg Olive oil, while the second group was received 8 ml/kg CCl4 [50% in olive oil] by gavages. After 48-h, the mice were anesthetized and killed to obtain blood and excise the liver. Gene's expression analysis in the liver tissue was carried out using cDNA microarray technique. Serum liver function tests, histopathological, histochemical and immunohistochemical examinations were also done. Serum transaminases [AST and ALT] activities exhibited significant increase with the induced hepatic pathological changes included typical inflammation and necrosis observed in CCl[4]-treated mice. The cDNA microarrays analysis revealed that 63 genes have clearly changed their levels of expression. Of these, 37 genes were up-regulated, and 26 genes were downregulated. Of the up-regulated genes were ribosomal, transcription, stress, proteolysis and peptidolysis encoded proteins. The most interesting up-regulated gene is metallothionine-1 gene which was observed by microarry and immunohistochemistry techniques. On the other hand, the down-regulated genes encoded proteins for xenobiotic metabolism, detoxification, lipid metabolism and hormones proteins. These results demonstrated that changes in gene expression profile correlate with the biochemical and pathological alterations in the liver in response to CCl[4] intoxication, and most of them can be related to CCl[4] mechanism of toxicity. However, the majority of the up-regulated genes are occurred in ribosomal protein. Furthermore, Mt-1 can be used as a biological marker for CCl[4] toxicity

Effects of profenofos on antioxidant enzymes activities and gastric mucosa in rats

Objective: In present study the effect of the organophosphorus insecticide, profenofos, on the antioxidant enzymes activities and mucosa of stomach was investigated in rats

Material and Methods: To evaluate these effects, the biochemical, histological, morphometrical, and histochemical studies on stomach were done. Animals were divided into three groups 10 animals of each. Control animals [group I] were administered vehicle. Treatment group animals [group II and III] were respectively administered oral doses of profenofos: 86.8 and 214.4 mg/kg b. wt. daily for 15 days

Results: The administration of profenofos caused a significant decrease in the levels of superoxide dismutase [SOD], glutathione peroxidase [GPx] and reduced glutathione [GSH], and an increase in the lipid peroxidation [LPO] level [p < 0.05]. The histopathological findings indicated that profenofos caused different alterations in stomach, including haemorrhagic areas in the mucosa and submucosa and degenerative changes. The histochemical examination showed noticeable reduction in polysaccharide materials of stomach; the cells of such organ displayed faint stain

Conclusion: Generally, profenofos caused extensive biochemical, histological, and histochemical injury. Such effects were relevant to the amount of dose given

L-carnitine and melatonin reverse CCl4 induced liver fibrosis in rats [histological and histochemical studies]

Carbontetrachloride [CCl4] 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 CCl4 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 CCl4 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 CCl4 only. Quantitative DNA image analysis showed that 3% of aneuploid cells could be noticed in liver of rats treated with CCl4 only. Histochemical results of rats treated with CCl4 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 L- carnitine or melatonin only. Both L–carnitine and melatonin were found to reverse CCl4 induced liver damage