Effect of verapamil on conversion of xanthine dehydrogenase to oxidase in ischemic rat liver

K. Ishii, S. Suita, Hideki Sumimoto

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The effect of organ flushing with the calcium entry blocker verapamil on the conversion of innocent enzyme xanthine dehydrogenase (XDH) to superoxide generating enzyme xanthine oxidase (XOD) in ischemic rat livers was studied. This enzyme conversion progressed over time in warm or cold ischemia. In non-flushed livers, the activities of XOD as percentages of XDH plus XOD after 6 h at 37°C and 6 days at 4°C were 80.3±5.2 and 31.6±2.1, respectively. In the livers flushed with Euro-Collins solution, the conversion was inhibited to 37.0±3.9% (P<0.001) after 6 h of warm ischemia, while this, inhibitory effect was not found in cold ischemia. Verapamil given through the portal vein on flushing further suppressed the conversion in both warm and cold ischemia (with 5.0 μM of verapamil, 21.2±5.8% (P<0.001) after 6 h of warm ischemia and 25.2±3.3% (P<0.01) after 6 days of cold ischemia). A similar effect was also obtained with the addition of 10 or 30 m M of EGTA instead of verapamil. In contrast, no inhibitory effect on conversion was obtained in livers flushed and homogenized with 10.0 μM of verapamil followed by incubation for 6 h at 37°C. In the livers that were flushed and stored at a warm temperature for 6h, verapamil reduced the increase of tissue lipid peroxidation product (P<0.02) after 15 min of reperfusion. Although the precise mechanisms of these inhibitory effects of verapamil on the enzyme conversion are still uncertain, it is though that organ flushing with verapamil might reduce the XOD-mediated postischemic reperfusion injury in livers subjected to prolonged ischemia.

Original languageEnglish
Pages (from-to)389-399
Number of pages11
JournalResearch in Experimental Medicine
Volume190
Issue number1
DOIs
Publication statusPublished - Dec 1 1990

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Xanthine Dehydrogenase
Verapamil
Oxidoreductases
Cold Ischemia
Warm Ischemia
Xanthine Oxidase
Liver
Enzymes
Egtazic Acid
Portal Vein
Reperfusion Injury
Superoxides
Lipid Peroxidation
Reperfusion
Ischemia
Calcium
Temperature

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Effect of verapamil on conversion of xanthine dehydrogenase to oxidase in ischemic rat liver. / Ishii, K.; Suita, S.; Sumimoto, Hideki.

In: Research in Experimental Medicine, Vol. 190, No. 1, 01.12.1990, p. 389-399.

Research output: Contribution to journalArticle

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abstract = "The effect of organ flushing with the calcium entry blocker verapamil on the conversion of innocent enzyme xanthine dehydrogenase (XDH) to superoxide generating enzyme xanthine oxidase (XOD) in ischemic rat livers was studied. This enzyme conversion progressed over time in warm or cold ischemia. In non-flushed livers, the activities of XOD as percentages of XDH plus XOD after 6 h at 37°C and 6 days at 4°C were 80.3±5.2 and 31.6±2.1, respectively. In the livers flushed with Euro-Collins solution, the conversion was inhibited to 37.0±3.9{\%} (P<0.001) after 6 h of warm ischemia, while this, inhibitory effect was not found in cold ischemia. Verapamil given through the portal vein on flushing further suppressed the conversion in both warm and cold ischemia (with 5.0 μM of verapamil, 21.2±5.8{\%} (P<0.001) after 6 h of warm ischemia and 25.2±3.3{\%} (P<0.01) after 6 days of cold ischemia). A similar effect was also obtained with the addition of 10 or 30 m M of EGTA instead of verapamil. In contrast, no inhibitory effect on conversion was obtained in livers flushed and homogenized with 10.0 μM of verapamil followed by incubation for 6 h at 37°C. In the livers that were flushed and stored at a warm temperature for 6h, verapamil reduced the increase of tissue lipid peroxidation product (P<0.02) after 15 min of reperfusion. Although the precise mechanisms of these inhibitory effects of verapamil on the enzyme conversion are still uncertain, it is though that organ flushing with verapamil might reduce the XOD-mediated postischemic reperfusion injury in livers subjected to prolonged ischemia.",
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AB - The effect of organ flushing with the calcium entry blocker verapamil on the conversion of innocent enzyme xanthine dehydrogenase (XDH) to superoxide generating enzyme xanthine oxidase (XOD) in ischemic rat livers was studied. This enzyme conversion progressed over time in warm or cold ischemia. In non-flushed livers, the activities of XOD as percentages of XDH plus XOD after 6 h at 37°C and 6 days at 4°C were 80.3±5.2 and 31.6±2.1, respectively. In the livers flushed with Euro-Collins solution, the conversion was inhibited to 37.0±3.9% (P<0.001) after 6 h of warm ischemia, while this, inhibitory effect was not found in cold ischemia. Verapamil given through the portal vein on flushing further suppressed the conversion in both warm and cold ischemia (with 5.0 μM of verapamil, 21.2±5.8% (P<0.001) after 6 h of warm ischemia and 25.2±3.3% (P<0.01) after 6 days of cold ischemia). A similar effect was also obtained with the addition of 10 or 30 m M of EGTA instead of verapamil. In contrast, no inhibitory effect on conversion was obtained in livers flushed and homogenized with 10.0 μM of verapamil followed by incubation for 6 h at 37°C. In the livers that were flushed and stored at a warm temperature for 6h, verapamil reduced the increase of tissue lipid peroxidation product (P<0.02) after 15 min of reperfusion. Although the precise mechanisms of these inhibitory effects of verapamil on the enzyme conversion are still uncertain, it is though that organ flushing with verapamil might reduce the XOD-mediated postischemic reperfusion injury in livers subjected to prolonged ischemia.

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