Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ubiquinol is the two-electron reduction product of ubiquinone (coenzyme Q(10) or CoQ(10)) and functions as an antioxidant in both mitochondria and lipid membranes. In humans and most mammals, including dogs, the predominant form of coenzyme Q is coenzyme Q(10), whereas the primary form in rodents is coenzyme Q(9) (CoQ(9)). Therefore, the subchronic toxicity of ubiquinol was evaluated and compared in Sprague-Dawley rats and beagle dogs. In the initial rat study, males and females were given ubiquinol at doses of 0, 300, 600, or 1200 mg/kg or ubiquinone at 1200 mg/kg by gavage for 13 weeks. This was followed by the second study, where females were given with doses of 75, 150, 200, or 300 mg/kg/day in order to determine a no observed adverse effect level (NOAEL). In the dog study, the test material was administered to males and females at dose levels of 150, 300, and 600 mg/kg, and ubiquinone was included at 600 mg/kg. Clinical observations, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, blood biochemistry, gross findings, organ weights, and histopathological findings were examined. In both species, determination of plasma and liver ubiquinol concentrations, measured as total coenzyme Q(10), were performed. There were no deaths or test article-related effects in body weight, food consumption, ophthalmology, urinalysis, or hematology in rats. Histopathological examinations revealed test article-related effects on the liver, spleen, and mesenteric lymph node in female rats but not in male rats. In the liver, fine vacuolation of hepatocytes was observed in the ubiquinol groups at 200 mg/kg and above. These changes were judged to be of no toxicological significance because they were not considered to induce cytotoxic changes. Microgranuloma and focal necrosis with accumulation of macrophages were observed in the ubiquinol groups at 300 mg/kg and above. These findings were accompanied by slight increases in blood chemistry enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and lactate dehydrogenase [LDH]), which was suggestive of either potential hepatotoxicity or a normal physiological response to ubiguinol loading. Microgranuloma, and focal necrosis were judged to be only adverse effects induced by test article based on their incidence and pathological characteristics. These changes observed in liver were thought due to uptake of the administered ubiquinol by the liver as an adaptive response to xenobiotics, and the microgranulomas and focal necrosis were considered the results of excessive uptake of ubiquinol, which exceeded the capacity for adaptive response. Based on these findings the NOAEL in rats was conservatively estimated to be 600 mg/kg/day for males and 200 mg/kg/day for females. In dogs, there were no deaths or ubiquinol-related toxicity findings during the administration period. No test article-related effects were observed in body weight, food consumption, ophthalmology, electrocardiogram, urinalysis, hematology, or blood chemistry. Histopathological examination revealed no effects attributable to administration of ubiquinol or ubiquinone in any organs examined. Based on these findings, a NOAEL for ubiquinol in male and female dogs was estimated to be more than 600 mg/kg/day under the conditions of this study.
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PMID:Subchronic oral toxicity of ubiquinol in rats and dogs. 1840 43

The antioxidant effect of CoQ(10) on N-nitrosodiethylamine (NDEA)-induced oxidative stress was investigated in mice. Food intake and body weight were similar in both CoQ(10) and control groups during the 3-week experimental period. NDEA significantly increased the activities of typical marker enzymes of liver function (AST, ALT and ALP) both in control and CoQ(10) groups. However, the increase of plasma aminotransferase activity was significantly reduced in the CoQ(10) group. Lipid peroxidation in various tissues, such as heart, lung, liver, kidney, spleen and plasma, was significantly increased by NDEA, but this increase was significantly reduced by 100 mg/kg of CoQ(10). Superoxide dismutase activity increased significantly upon NDEA-induced oxidative stress in both the control and CoQ(10) groups with the effect being less in the CoQ(10) group. Catalase activity decreased significantly in both the control and CoQ(10) groups treated with NDEA, again with the effect being less in the CoQ(10) group. The lesser effect on superoxide dismutase and catalase in the NDEA-treated CoQ(10) group is indicative of the protective effect CoQ(10). Thus, CoQ(10) can offer useful protection against NDEA-induced oxidative stress.
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PMID:Antioxidant Effect of CoQ(10) on N-nitrosodiethylamine-induced Oxidative Stress in Mice. 1988 17