Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatty livers of obese fa/fa rats are vulnerable to injury when challenged by insults such as endotoxin, ischemia-reperfusion or acute ethanol treatment. The objective of this study was to evaluate whether a high-fat diet can act as a "second hit" and cause progression to liver injury in obese fa/fa rats compared with lean Fa/? rats. Accordingly, obese fa/fa rats and their lean littermates were fed a diet low in fat (12% of total calories) or a diet with 60% calories as lard for 8 weeks. Hyperglycemia and steatohepatitis occurred in the fa/fa rats fed the high-fat diet. This was accompanied by liver injury as assessed by alanine aminotransferase, hematoxilin and eosin staining, increased TNFalpha and stellate cell-derived TGFbeta, collagen deposition, and up-regulation of alpha-smooth muscle actin. Active MMP13 decreased in fa/fa rats independently of the diet, and TIMP1 expression increased with the high-fat diet, especially in fa/fa rats. Although UCP2 expression was higher in fa/fa rats regardless of the diet, minor changes in ATP levels were observed. Oxidative stress occurred in the fa/fa rats fed the high-fat diet as lipid peroxidation and protein carbonyls were elevated, while glutathione and antioxidant enzymes were very low. Expression and activity of cytochrome P450 2E1 and xanthine oxidase activity were down-regulated in fa/fa compared with Fa/? rats, and no effect was seen by the high-fat diet. However, NADPH oxidase activity increased 2.5-fold in fa/fa rats fed with the high-fat diet. In summary, a high-fat diet induces liver injury in fa/fa rats leading to periportal fibrosis. A role for oxidative stress is suggested via increased NADPH oxidase activity, lipid peroxidation, protein carbonyl formation, and low antioxidant defense.
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PMID:A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. 1552 5

Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders, most notably preeclampsia (PE) and intrauterine growth restriction (IUGR). Oxidative stress occurs when accumulation of reactive oxygen species (ROS) damages DNA, proteins and lipids, an outcome that is limited by antioxidant enzymes; mitochondrial uncoupling protein 2 (UCP2) may also limit oxidative stress by reducing ROS production. Here we characterized placental antioxidant defenses during normal gestation and following glucocorticoid-induced IUGR. Placentas were collected on Days 16 and 22 of normal rat pregnancy (term = Day 23) and at Day 22 after dexamethasone treatment from Day 13. Expression of several genes encoding antioxidant enzymes (Sod1, Sod2, Sod3, Cat, Gpx3, Txn1, Txnrd1, Txnrd2, and Txnrd3) and Ucp2 was measured by quantitative RT-PCR in the labyrinth (LZ) and junctional zones (JZ) of the placenta. Expression of Sod1 and Ucp2 mRNAs and the activity of xanthine oxidase, a source of ROS, all increased from Days 16 to 22 in both placental zones, whereas Sod2 and Gpx3 increased only in the rapidly growing LZ. In contrast, Sod3 and Txnrd1 expression fell in the LZ over this period, whereas total superoxide dismutase activity remained stable. Dexamethasone treatment reduced fetal-placental growth and LZ expression of Ucp2 but increased JZ expression of Txn1. Indices of placental oxidative damage (TBARS, F(2)-isoprostanes, and 8-OHdG) did not change with gestational age or dexamethasone, indicative of adequate antioxidant protection. Overall, our data suggest that the rat placenta is protected from oxidative stress by the dynamic zone- and stage-dependent expression of antioxidant defense genes.
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PMID:Antioxidant defenses in the rat placenta in late gestation: increased labyrinthine expression of superoxide dismutases, glutathione peroxidase 3, and uncoupling protein 2. 2039 69

The superoxide-dependent chemiluminescent intensity in different brain regions was examined in ex vivo tissue slices of rat brain during normoxia and hypoxia-reoxygenation with lucigenin. The chemiluminescent intensity increased during reoxygenation after hypoxic treatment. There was a higher level of chemiluminescent intensity in the hippocampus during normoxia, and a lower level in the white matter during normoxia and hypoxia-reoxygenation. A weak correlation was found between the chemiluminescent intensity and the glucose uptake rate during normoxia. Then we examined whether hypoxic strength correlates to superoxide generation. The chemiluminescent intensity increased in a hypoxic strength-dependent manner. The generation mechanism of superoxide was examined using carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, genipin, an inhibitor for uncoupling protein-2, alloprinol, a xanthine oxidase inhibitor, or apocynin, an NADPH oxidase inhibitor. The chemiluminescent signal was significantly inhibited by CCCP under normoxic condition and enhanced by genipin during normoxia and hypoxia-reoxygenation, but not by allopurinol or apocynin. These results suggest that superoxide generation is high in the hippocampus during normoxia and low in the white matter during normoxia and hypoxia-reoxygenation, superoxide generation in the hypoxia-reoxygenation brain correlates with the strength of hypoxia influenced by oxygen delivery, and mitochondrion is the major sites of intracellular superoxide generation.
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PMID:Superoxide generation in different brain regions of rats during normoxia and hypoxia-reoxygenation. 2314 23

This work investigates the effects of oxidative stress due to exhaustive training on uncoupling protein 2 (UCP2) and Bcl-2/Bax in rat skeletal muscles. A total of 18 Sprague-Dawley female rats were randomly divided into three groups: the control group (CON), the trained control group (TC), and the exhaustive trained group (ET). Malondialdehyde (MDA), superoxide dismutase (SOD), xanthine oxidase (XOD), ATPase, UCP2, and Bcl-2/Bax ratio in red gastrocnemius muscles were measured. Exhaustive training induced ROS increase in red gastrocnemius muscles, which led to a decrease in the cell antiapoptotic ability (Bcl-2/Bax ratio). An increase in UCP2 expression can reduce ROS production and affect mitochondrial energy production. Thus, oxidative stress plays a significant role in overtraining.
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PMID:Exhaustive training increases uncoupling protein 2 expression and decreases Bcl-2/Bax ratio in rat skeletal muscle. 2336 96