ABSTRACT
This study is to investigate the therapeutic effect and mechanism of indole-3-carbinol (I3C) on pig serum-induced liver fibrosis of rats. The liver fibrotic model of rats was induced by pig serum. After models were successfully established, rats in the treatment groups were administered with I3C through intraperitoneal injection or curcumin by intragastric administration, daily for 17 days. Hepatic hydroxyproline (Hyp) content was measured. The liver histology and immunohistochemistry with a-smooth muscle actin (alpha-SMA) were assayed. Hepatic stellate cells line, HSC-T6 was incubated with different concentrations of I3C (25, 50, and 100 micromol x L(-1)) for 24 h. The effect of I3C on cell apoptosis was identified by FITC-Annexin V/PI double labeled assay. And the mRNA expressions of Bax and Bcl-2 were measured by real time RT-PCR. The results showed that hepatic content of Hyp decreased by I3C treatment, as compared with the fibrotic model control. Histopathological changes, such as steatosis, necrosis, deposition of collagenous fiber reduced remarkably and the expression of alpha-SMA was significantly down-regulated in the I3C-treated groups (P < 0.01). Apoptosis analysis showed that I3C significantly increased HSC-T6 apoptosis rate and the expressional ratio of Bax to Bcl-2. The results indicated that I3C could effectively cure pig serum-induced liver fibrosis in vivo by inducing HSC apoptosis and promoting ECM degradation.
Subject(s)
Animals , Male , Rats , Actins , Metabolism , Apoptosis , Cell Line , Collagen , Metabolism , Curcumin , Pharmacology , Enzyme Inhibitors , Pharmacology , Hepatic Stellate Cells , Cell Biology , Hydroxyproline , Metabolism , Indoles , Pharmacology , Liver , Metabolism , Pathology , Liver Cirrhosis, Experimental , Metabolism , Pathology , Proto-Oncogene Proteins c-bcl-2 , Genetics , Metabolism , RNA, Messenger , Metabolism , Rats, Wistar , Serum , Swine , Blood , bcl-2-Associated X Protein , Genetics , MetabolismABSTRACT
<p><b>AIM</b>To search for new derivatives of diclofenac (DC) having higher potency than the parent drug and lacking its undesirable effects.</p><p><b>METHODS</b>Coupling DC with NO donor 3-hydroxymethyl-4-phenylfuroxan and its isomer through esterification, evaluating anti-inflammatory and analgesic activities, observing side effects in the rat gastrointestinal (GI) tract and assessing NO releasing ability both in vitro and in vivo.</p><p><b>RESULTS</b>Fifteen new compounds including nine target ones (II1-9) were synthesized, and their structures were determined by IR, 1HNMR, MS and elemental analysis. Compounds II3 and II9 showed anti-inflammatory activity comparable to DC. Compound II2 showed stronger anti-inflammatory and analgesic activities and less GI side effect than DC, and released NO in vivo.</p><p><b>CONCLUSION</b>Compound II2 is worthy to be intensively studied.</p>
Subject(s)
Animals , Mice , Rats , Analgesics , Pharmacology , Therapeutic Uses , Anti-Inflammatory Agents, Non-Steroidal , Pharmacology , Therapeutic Uses , Cyclic N-Oxides , Chemistry , Pharmacology , Diclofenac , Pharmacology , Therapeutic Uses , Digestive System , Edema , Drug Therapy , Gastrointestinal Hemorrhage , Molecular Structure , Nitric Oxide , Metabolism , Nitric Oxide Donors , Chemistry , Pharmacology , Oxadiazoles , Chemistry , Pharmacology , Pain Threshold , Structure-Activity RelationshipABSTRACT
Guinea pigs were given orally with a daily dose of 0.5 mg ascorbic acid per 100 g body weight 20 days before and 4 days after a whole-body r-irradiation and then injected subcutaneously with 10 mg ascorbic acid at 24 hours intervals. During the injection period, the daily urinary output of total ascorbic acid in the animals irradiated with 500 or 1000 r was significantly higher than that in controls, but the difference of 24 hours excretions of total ascorbic acid between the group irradiated with 150 or 250 r and the control group was not statistically significant.As shown in the urinary output of dehydroascorbic acid and diketo- gulonic acid estimated by our modified Roe's method, r-irradiation has no effect on its excretion in guinea pigs and rats.The levels of ascorbic acid in plasma, spleen and adrenals were significantly lower in the irradiated group than in the control group, but might increase with the increase of the injected dose of ascorbic acid.