antifibrotic effect of Zilla spinosa extracts targeting apoptosis in CCl4-induced liver damage in rats

Background/aim: Liver fibrosis and its end-stage cirrhosis are the main reasons of morbidity and mortality all over the world. The current study aimed to evaluate the efficacy of Zilla spinosa [Z. spinosa] on CCl4-induced liver fibrosis, apoptosis, and oxidative stresses in rats

Materials and methods: Extract of aerial part of Z. spinosa was used in this study. Thirty male Sprague Dawley rats were enrolled in this study and divided into five groups [six each]: group 1 served as control and groups 2-5 were treated with CCl4 [1ml/kg intraperitoneal twice a week for 8 weeks], where group 2 served as a control positive, group 3 received silymarin [50?mg/kg] daily, and groups 4 and 5 were administrated with Z. spinosa [100 and 200 mg/kg, respectively] daily for 8 weeks. At the end of each experiment, liver function tests were analyzed in serum, whereas malondialdehyde [MDA], Nitric oxide [NO], Glutathione [GSH], and hydroxyproline [HA] were analyzed in liver tissues. Liver fibrosis was confirmed histopathologically, and collagen content, caspase-3, and alpha-smooth muscle actin [alpha-SMA] were assayed immunhistochemically

Results: Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, MDA, NO, and HA levels were increased [P<0.05], whereas total protein and GSH were decreased [P<0.05] in CCl4-administrated rats. Histopathological results showed loss of lobular structure, fibrosis with expansion of portal tract by fibrous tissue together with inflammatory changes confined to portal tract and central vein, and intense centrilobular necrosis and remarkable fatty hydropic degeneration. In addition, extensive accumulation of connective tissue, marked depletion of glycogen, strong expression of alpha-SMA, and increased of caspase-3 were found in CCl4-administrated rats. Oral administration of Z. spinosa at 100 or 200 mg/kg restored the normal levels of liver function parameters, MDA, NO and GSH; decreased HA; and reduced collagen, glycogen content, caspase-3, and alpha-SMA in liver tissue of rats. The high dose of 200 mg/kg showed more potent effect than low dose of 100 mg/kg when compared with silymarin treatment group

Conclusion:The present study clarified that Z. spinosa extract has antioxidant and antiapoptotic properties in CCl4-induced liver fibrosis in rats, and may be able to exert a therapeutic effect on developing hepatic fibrosis; moreover, high dose of 200?mg/kg appeared to be more potent than low dose [100 mg/kg]

Combinational effect of 5-flourouracil and resveratrol against N-nitroso-N-methyl urea induced colorectal cancer

Background: colorectal cancer is considered to be the third most common cause of deaths in both men and women. The incidence of colorectal cancer cases has been rising at an alarming rate. In most cases, colon cancer treatment involves chemotherapy. However, toxicity and tumor cell drug resistance are outstanding obstacles to this treatment. Scientific studies suggested that combining certain chemotherapy treatments with specific antioxidants at defined dosages can improve drug efficacy or may reduce side effects severity.5-Fluorouracil, which is used in the treatment of breast, stomach and pancreatic cancer, remains the cornerstone of CRC treatment, although widely used in combination with several other drugs. Many effective drugs, including those actually used for cancer treatment, have been developed from botanical sources. Resveratrol is a pleiotropic phytochemical which is belong to the stilbene family. Although, it is only significantly present in grape products. Many preclinical studies investigated its anticancer properties in a plethora of cellular and animal models

Aim of the work: in the present study, the anticancer effects of Resveratrol alone or combined with 5-Fu were assessed on experimentally induced colorectal cancer in rats

Results: the results of this study indicated that RES had a better therapeutic effect against N-methylnitrosourea induced colorectal cancer than 5-Fu alone and when in combination with each other they diminished the cytotoxic effect of 5-Fu and enhanced normal histological appearance of colon tissue, which could be a promising alternative for resistant colorectal cancer. However, the exact mechanisms involved needs to be further explored

Conclusion: our results suggested that both natural compounds could be in the future a possible alternative to enhance the efficiency of 5-Fu in resistant colon cancer cells. This study supports the potential of plant extracts as source of bioactive compounds with biomedical applications

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