Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite pathophysiological similarities to alcoholic liver disease, susceptibility to acetaminophen hepatotoxicity in metabolic syndrome-related nonalcoholic steatohepatitis (NASH) has not been well elucidated. In this study, therefore, we investigated acetaminophen-induced liver injury in KK-A(y) mice, an animal model of metabolic syndrome. Twelve-week-old male KK-A(y) and C57Bl/6 mice were injected intraperitoneally with 300 or 600 mg/kg acetaminophen, and euthanized 6 h later. Liver histology was assessed, and hepatic expression of 4-hydroxy-2-nonenal was detected by immunohistochemistry. Levels of reduced glutathione were determined spectrophotometrically. Phosphorylation of c-Jun NH(2)-terminal kinase (JNK) was analyzed by Western blotting. Hepatocytes were isolated from both strains by collagenase perfusion, and cell death and oxidative stress were measured fluorometrically by use of propidium iodide and 5-(and-6)-chloromethyl-2'7'-dichloro-dihydrofluorescein diacetate acetyl ester, respectively. Acetaminophen induced more severe necrosis and apoptosis of hepatocytes in KK-A(y) mice than in C57Bl/6 mice and significantly increased serum alanine aminotransferase levels in KK-A(y) mice. Acetaminophen-induction of 4-hydroxy-2-nonenal in the liver was potentiated, whereas the levels of reduced glutathione in liver were lower in KK-A(y) mice. Acetaminophen-induced phosphorylation of JNK in the liver was also enhanced in KK-A(y) mice. Exposure to 20 microM tert-butyl hydroperoxide did not kill hepatocytes isolated from C57Bl/6 mice but induced cell death and higher oxidative stress in hepatocytes from KK-A(y) mice. These results demonstrated that acetaminophen toxicity is increased in diabetic KK-A(y) mice mainly due to enhanced oxidative stress in hepatocytes, suggesting that metabolic syndrome-related steatohepatitis is an exacerbating factor for acetaminophen-induced liver injury.
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PMID:Diabetic KK-A(y) mice are highly susceptible to oxidative hepatocellular damage induced by acetaminophen. 2053 6

Although advanced oxidation protein products (AOPPs) have been reported as the most appropriate parameter for determination of oxidative stress in patients with metabolic syndrome (MetS), a direct comparison between protein and lipid peroxidation has not been performed yet. The aim of this study was to compare protein peroxidation with lipid peroxidation measured by 2 different methodologies (tert-butyl hydroperoxide-initiated chemiluminescence and ferrous oxidation-xylenol orange assay). The hypothesis of this study was that AOPPs would be more related to MetS than to oxidative markers of lipid peroxidation. This cross-sectional study evaluated 76 patients with MetS and 20 healthy subjects. Prooxidant-antioxidant index (PAI) assessed as AOPP/total radical-trapping antioxidant parameter ratio progressively increased (P < .05) according to the number of MetS components, whereas AOPPs and total radical-trapping antioxidant parameter increased (P < .05) when 5 components were compared with 3 components. Spearman test showed a positive correlation between AOPPs and waist circumference (r = 0.318, P < .01), fasting glucose (r = 0.250, P < .05), homeostasis model assessment insulin resistance (r = 0.043, P < .01), triacylglycerol (r = 0.713, P < .0001), highly sensitive C-reactive protein (r = 0.275, P < .05), and uric acid (r = 0.356, P < .01), whereas there was an inverse correlation with high-density lipoprotein cholesterol (r = -0.399, P < .001). Prooxidant-antioxidant index demonstrated a positive correlation with waist circumference (r = 0.386, P < .01), fasting glucose (r = 0.388, P < .01), fasting insulin (r = 0.344, P < .05), homeostasis model assessment insulin resistance (r = 0.519, P < .001), triacylglycerol (r = 0.687, P < .0001), highly sensitive C-reactive protein (r = 0.278, P < .05), and uric acid (r = 0.557, P < .0001), whereas there was an inverse correlation with high-density lipoprotein cholesterol (r = -0.480, P < .0001). In conclusion, protein peroxidation determined by AOPPs, and especially by PAI, is more related to MetS components than lipid peroxidation. In addition, PAI progressively increased with the number of MetS components.
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PMID:Advanced oxidation protein products are more related to metabolic syndrome components than biomarkers of lipid peroxidation. 2625 93

Fermented lentil (FL) produced using L. plantarum and Savinase in alkaline conditions relieves metabolic alterations and oxidative stress in Zucker rats with metabolic syndrome. Here, we investigated the effect of up scaling the fermentation process on chemical composition and biological activity of FL. Moreover, we studied the molecular mechanisms by which FL exert a cytoprotective effect against oxidative stress in tert-butyl hydroperoxide (t-BHP)-challenged RAW264.7 macrophages. Up-scale production reduced overall biological effectiveness of FL with the exception of inhibition of intracellular ROS generation. FL prevented t-BHP-induced cytotoxicity and intracellular accumulation of reactive oxygen species through activation of catalase expression via SAPK/JNK phosphorylation and Nrf2 nuclear translocation. Different oligopeptides, phenolic acids and flavonols were identified as contributors of the observed effects. To the best of our knowledge, we reported for the first time that FL attenuates oxidative stress cellular damage via activation of SAPK/JNK phosphorylation, Nrf2 nuclear translocation and antioxidant enzymes expression.
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PMID:Pilot-scale produced fermented lentil protects against t-BHP-triggered oxidative stress by activation of Nrf2 dependent on SAPK/JNK phosphorylation. 3037 4