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)

The killing of blood-stage malaria parasites in vivo has been attributed to reactive intermediates of oxygen (ROI) and of nitrogen (RNI). However, in the case of the latter, this contention is challenged by recent observations that parasitemia was not exacerbated in nitric oxide synthase (NOS) knockout (KO) (NOS2-/- or NOS3-/-) mice or in mice treated with NOS inhibitors. We now report that the time course shows that Plasmodium chabaudi parasitemia in NADPH oxidase KO (p47phox-/-) mice also was not exacerbated, suggesting a minimal role for ROI-mediated killing of blood-stage parasites. It is possible that the production of protective antibodies during malaria may mask the function of ROI and/or RNI. However, parasitemia in B-cell-deficient JH-/- x NOS2-/- or JH-/- x p47phox-/- mice was not exacerbated. In contrast, the magnitude of peak parasitemia was significantly enhanced in p47phox-/- mice treated with the xanthine oxidase inhibitor allopurinol, but the duration of patent parasitemia was not prolonged. Whereas the time course of parasitemia in NOS2-/- x p47phox-/- mice was nearly identical to that seen in normal control mice, allopurinol treatment of these double-KO mice also enhanced the magnitude of peak parasitemia. Thus, ROI generated via the xanthine oxidase pathway contribute to the control of ascending P. chabaudi parasitemia during acute malaria but alone are insufficient to suppress parasitemia to subpatent levels. Together, these results indicate that ROI or RNI can contribute to, but are not essential for, the suppression of parasitemia during blood-stage malaria.
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PMID:Suppression of Plasmodium chabaudi parasitemia is independent of the action of reactive oxygen intermediates and/or nitric oxide. 1550 65

This study investigated the effect of astaxanthin (ASX; 3,3-dihydroxybeta, beta-carotene-4,4-dione), a water-dispersible synthetic carotenoid, on liver ischemia-reperfusion (IR) injury. Astaxanthin (5 mg/kg/day) or olive oil was administered to rats via intragastric intubation for 14 consecutive days before the induction of hepatic IR. On the 15th day, blood vessels supplying the median and left lateral hepatic lobes were occluded with an arterial clamp for 60 min, followed by 60 min reperfusion. At the end of the experimental period, blood samples were obtained from the right ventricule to determine plasma alanine aminotransferase (ALT) and xanthine oxidase (XO) activities and animals were sacrificed to obtain samples of nonischemic and postischemic liver tissue. The effects of ASX on IR injury were evaluated by assessing hepatic ultrastructure via transmission electron microscopy and by histopathological scoring. Hepatic conversion of xanthine dehygrogenase (XDH) to XO, total GSH and protein carbonyl levels were also measured as markers of oxidative stress. Expression of NOS2 was determined by immunohistochemistry and Western blot analysis while nitrate/nitrite levels were measured via spectral analysis. Total histopathological scoring of cellular damage was significantly decreased in hepatic IR injury following ASX treatment. Electron microscopy of postischemic tissue demonstrated parenchymal cell damage, swelling of mitochondria, disarrangement of rough endoplasmatic reticulum which was also partially reduced by ASX treatment. Astaxanthine treatment significantly decreased hepatic conversion of XDH to XO and tissue protein carbonyl levels following IR injury. The current results suggest that the mechanisms of action by which ASX reduces IR damage may include antioxidant protection against oxidative injury.
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PMID:Effect of astaxanthin on hepatocellular injury following ischemia/reperfusion. 1990 May

Oxidative stress and excessive nitric oxide production via induction of inducible nitric oxide synthase (NOS)-2 have been shown in the pathogenesis of liver ischemia-reperfusion (IR) injury. Neutral sphingomyelinase (N-SMase)/ceramide pathway can regulate NOS2 expression therefore this study determined the role of selective N-SMase inhibition on nitrative and oxidative stress markers following liver IR injury. Selective N-SMase inhibitor was administered via intraperitoneal injections. Liver IR injury was created by clamping blood vessels supplying the median and left lateral hepatic lobes for 60 min, followed by 60 min reperfusion. Nitrative and oxidative stress markers were determined by evaluating NOS2 expression, protein nitration, nitrite/nitrate levels, 4-hydroxynonenal (HNE) formation, protein carbonyl levels and xanthine oxidase/xanthine dehydrogenase (XO/XDH) activity. Levels of sphingmyelin and ceramide in liver tissue were determined by an optimized multiple reaction monitoring method using ultra-fast liquid chromatography coupled with tandem mass spectrometry (MS/MS). Spingomyelin levels were significantly increased in all IR groups compared to controls. Treatment with a specific N-SMase inhibitor significantly decreased all measured ceramides in IR injury. NOS2 expression, nitrite/nitrate levels and protein nitration were significantly greater in IR injury and decreased with N-SMase inhibition. Treatment with a selective N-SMase inhibitor significantly decreased HNE formation, protein carbonyl levels and the hepatic conversion of XO. Data confirm the role of nitrative and oxidative injury in IR and highlight the protective effect of selective N-SMase inhibition. Future studies evaluating agents blocking N-SMase activity can facilitate the development of treatment strategies to alleviate oxidative injury in liver I/R injury.
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PMID:Inhibition of neutral sphingomyelinase decreases elevated levels of nitrative and oxidative stress markers in liver ischemia-reperfusion injury. 2707 55