Role of xanthine oxidase inhibitor as free radical scavenger: A novel mechanism of action of allopurinol and oxypurinol in myocardial salvage

Das, Dipak K.; Engelman, Richard M.; Clement, Ronald; Otani, Hajime; Prasad, M. R. N.; Rao, P. Syamasundar

doi:10.1016/0006-291x(87)91112-0

Cited by 185 publications

(77 citation statements)

References 9 publications

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“…3A and 3B). These facts are consistent with the attenuation of the O 2 -· current and Q. Allopurinol itself has ROS scavenging effects (Das et al, 1987;Moorhouse et al, 1987) and can cross blood brain barrier (Palmer et al, 1993). These mechanisms in addition to XO inhibition acted on the suppression of brain and plasma MDA.…”

Section: Discussionsupporting

confidence: 84%

“…It has been suggested that there is a positive feedback loop in the O 2 -· generation associated with XO (McNally et al, 2005). Allopurinol itself has ROS scavenging effects (Das et al, 1987;Moorhouse et al, 1987), so that allopurinol might suppress the positive feedback loop of O 2 -· generation due to both inhibition of XO and the ROS scavenging effect.…”

Section: Discussionmentioning

confidence: 99%

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Xanthine oxidase is one of the major sources of superoxide anion radicals in blood after reperfusion in rats with forebrain ischemia/reperfusion

et al. 2009

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Xanthine oxidase is one of the major sources of superoxide anion radicals in blood after reperfusion in rats with forebrain ischemia/reperfusion

et al. 2009

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“…These results suggest that oxygen free radicals produced by XOD increasing in the liver of CC14-treated rats cause the enhancements of increase in TBARS concentration and decrease in GSH concentration in the liver, which contributes to the progression of CC14-induced acute liver injury. It has been shown in vitro that allopurinol and its main in vivo metabolite, oxypurinol, function as a scavenger of oxygen free radicals [49,50] . However, Klein et al…”

Section: Discussionmentioning

confidence: 99%

Contribution of Xanthine Oxidase-Derived Oxygen Free Radicals to the Development of Carbon Tetrachloride-Induced Acute Liver Injury in Rats

Ohta

Kongo-Nishimura

Imai

et al. 2003

J. Clin. Biochem. Nutr.

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Summary We examined how oxygen free radicals derived from xanthine oxidase (XOD) contribute to the development of carbon tetrachloride (CCl4)-induced acute liver injury in rats. In rats treated with CCl4 (1 ml/kg), liver injury appeared 3 h after the treatment and developed by 24 h, judged from the serum levels of transaminases. Hepatic and serum XOD activities and serum uric acid concentration did not change 6 h after CCl4 treatment, but they all increased at 12 h and further increased at 24 h. An increase in the concentration of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, and decreases in reduced glutathione concentration and Cu,Zn-superoxide dismutase (SOD) activity, but not Mn-SOD activity, were observed in the liver at b h after CCl4 treatment and these changes were further enhanced at 24h. When allopurinol (50 mg/kg), an XOD inhibitor, was administered to CCl4-treated rats 6 h after CCl4 treatment, liver injury progression was prevented with attenuation of increased hepatic and serum XOD activities, serum uric acid concentration, and hepatic TBARS concentration and decreased hepatic reduced glutathione concentration and Cu,Zn-SOD activity at 24 h after CCl4 treatment. These results indicate that XOD-derived oxygen free radicals contribute to the progression of CCl4-induced acute liver injury in rats both by stimulating hepatic lipid peroxidation and by disrupting hepatic antioxidant defense system.

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“…For example, the replacement of molybdenum with tungsten leads to the inhibition of XOD activity; however, the tungsten-enriched diet can also influence other molybdenum-dependent enzymes (21,23). Likewise, oxypurinol not only inhibits XOD, it may also directly scavenge ROS (9). Although both the tungsten diet and oxypurinol inhibit XOD, both treatments have other potential nonspecific effects that may also impact hydraulic conductivity and lead to the observed differences in the magnitude of their effects.…”

Section: Postcapillary Venular Endothelial Cells Are Especially Suscementioning

confidence: 99%

Ischemia-reperfusion injury in rats affects hydraulic conductivity in two phases that are temporally and mechanistically separate

Victorino¹,

Ramírez²,

Chong³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Victorino GP, Ramirez RM, Chong TJ, Curran B, Sadjadi J. Ischemia-reperfusion injury in rats affects hydraulic conductivity in two phases that are temporally and mechanistically separate. Am J Physiol Heart Circ Physiol 295: H2164 -H2171, 2008. First published September 12, 2008 doi:10.1152/ajpheart.00419.2008 injury is a major insult to postcapillary venules. We hypothesized that IR increases postcapillary venular hydraulic conductivity and that IR-mediated changes in hydraulic conductivity result from temporally and mechanistically separate processes. A microcannulation technique was used to determine hydraulic conductivity (Lp) in rat mesenteric postcapillary venules serially throughout ischemia (45 min) and reperfusion (5 h) induced by superior mesenteric artery occlusion and release. Mesenteric IR resulted in a biphasic increase in Lp. White blood cell (WBC) adhesion slowly increased with maximal adhesion corresponding to the second peak (P Ͻ 0.005). After IR, tissue was harvested for RT-PCR analysis of ICAM-1, E-selectin, and P-selectin mRNA. Intercellular adhesion molecule-1 (ICAM-1) mRNA in the gut showed the most significant upregulation. Quantitative real-time PCR revealed that ICAM-1 mRNA was upregulated 60-fold in the gut. An ICAM-1 antibody was therefore used to determine the effect of WBC adhesion on Lp during IR. ICAM-1 inhibition attenuated Lp during the first peak and completely blocked the second peak (P Ͻ 0.005). When rats were fed a tungsten diet to inhibit xanthine oxidase and then underwent IR, Lp was dramatically attenuated during the first peak and mildly decreased the second peak (P Ͻ 0.005). Inhibition of xanthine oxidase by oxypurinol decreased Lp during IR by over 60% (P Ͻ 0.002). Tempol, a superoxide dismutase mimetic, decreased Lp during IR by over 30% (P Ͻ 0.01). We conclude that IR induces a biphasic increase in postcapillary hydraulic conductivity. Reactive oxygen species impact both the first transient peak and the sustained second peak. However, the second peak is also dependent on WBC-endothelial cell adhesion. These serial measurements of postcapillary hydraulic conductivity may lead the way for optimal timing of pharmaceutical therapies in IR injury. microvascular permeability; reactive oxygen species; intercellular adhesion molecule-1

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Role of xanthine oxidase inhibitor as free radical scavenger: A novel mechanism of action of allopurinol and oxypurinol in myocardial salvage

Cited by 185 publications

References 9 publications

Xanthine oxidase is one of the major sources of superoxide anion radicals in blood after reperfusion in rats with forebrain ischemia/reperfusion

Xanthine oxidase is one of the major sources of superoxide anion radicals in blood after reperfusion in rats with forebrain ischemia/reperfusion

Contribution of Xanthine Oxidase-Derived Oxygen Free Radicals to the Development of Carbon Tetrachloride-Induced Acute Liver Injury in Rats

Ischemia-reperfusion injury in rats affects hydraulic conductivity in two phases that are temporally and mechanistically separate

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