Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malotilate, diisopropyl 1,3-dithiol-2-ylidenemalonate, is a relatively recently synthesized hepatotrophic chemical substance. Its inhibitory effect on rat liver cirrhosis induced by carbon tetrachloride (CCl4) was biochemically and morphologically investigated for 10 weeks, since this chemical had been reported to suppress liver damage caused by CCl4 or in vitro collagenogenesis of human fibroblasts. Concomitant administration of malotilate with CCl4 completely suppressed liver cell necrosis and markedly inhibited fatty change of hepatocytes in the first three weeks of the experiment. During the six to ten weeks of the experimental period, liver cirrhosis was perfectly inhibited by malotilate. Previously established liver cirrhosis, however, could not be normalized by malotilate treatment. Precise mechanism of the inhibitory effect of malotilate on liver cirrhosis is not elucidated, but this substance is clearly effective for preventing liver cell damage and/or liver cirrhosis caused by CCl4.
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PMID:Malotilate completely inhibits CCl4-induced liver cirrhosis in rats: biochemical and morphological analysis. 129 70

Macrophages isolated from fluids of patients with liver cirrhosis mainly generated the 5-lipoxygenase products leukotriene B4 and 5-monohydroxyeicosatetraenoic acid. The cyclooxygenase products 6-keto-PGF1 alpha and thromboxane B2 were the most important prostaglandin-like substances. Malotilate, an anti-fibrotic substance, selectively inhibited the 5-lipoxygenase, whereas both the 12- and the 15-lipoxygenase pathways were stimulated. The effects of malotilate on eicosanoid production differ from those of known lipoxygenase inhibitors. Such differential effects have not been reported previously.
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PMID:Differential effects of malotilate on 5-, 12- and 15-lipoxygenase in human ascites cells. 253 38

Malotilate, a hepatotropic agent, was given to 39 cirrhotic patients for more than 32 weeks. The serial changes in the serum levels of hepatic fibrogenesis markers, such as procollagen type III N-terminal peptides (P-III-N-P) and immunoreactive prolyl hydroxylase beta-subunit (IR-BPH) were analyzed. Serum albumin levels, transaminase and choline esterase activities and the Normotest values were found to be significantly improved by malotilate treatment. The levels of both serum markers of hepatic fibrogenesis were also significantly reduced by malotilate. The prognoses of the decompensated liver cirrhosis patients treated with malotilate were significantly better than those who did not receive malotilate. These results indicate that the effects of malotilate on chronic liver diseases are not simply biocosmetic, but rather are related to an improvement in the basal changes of the liver, including a decrease in the fibrogenetic stimulus. These effects of malotilate improved the prognosis of liver cirrhosis.
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PMID:Effects of malotilate treatment on the serum markers of hepatic fibrogenesis in liver cirrhosis. 285 77

Malotilate, a sulphur-containing compound with antifibrotic and hepatoprotective properties in several animal models, has been investigated in cirrhotic patients. Nine patients with cirrhosis of various aetiologies and severity, and 4 healthy volunteers, participated in a pharmacokinetic study. After a single dose of 500 mg malotilate p.o. peak malotilate plasma concentration measured by GC-MS was 35 times higher in patients (median 0.70 micrograms/ml) than in controls (median 0.019 micrograms/ml). The median apparent oral clearance was approximately 50 times lower in cirrhotics (median 2.21/min) than in healthy volunteers (1181/min). The apparent oral clearance was significantly correlated with indicators of portal-systemic shunting, such as the 2-h postprandial serum bile acids and the bioavailability of oral nitroglycerine. Urinary output of the glucuronidated metabolite-(M3), measured by HPLC, was normal in patients, whereas recovery of metabolite-M6 (resulting from ring opening and loss of sulphur) was reduced. Six patients in an open 6-month trial received malotilate 200 mg t.i.d. for 2 months and 400 mg t.i.d. for 4 months. The thrombocyte count increased and serum ferritin level fell in all patients, and serum cholinesterase rose and IgA decreased in 5 of 6. The other indicators of liver function did not show a significant change. Dry skin was the only possible adverse effect. It is concluded that first-pass elimination of malotilate is dramatically reduced in cirrhotics, and that a smaller amount of the drug reaches the liver in such patients. Malotilate was well tolerated, even in patients with advanced disease.
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PMID:Treatment of liver disease with malotilate. A pharmacokinetic and pharmacodynamic phase II study in cirrhosis. 374 16