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)

In this study the role of free radicals, lipid peroxidation, and neutrophil infiltration as mediators of ischemia and reperfusion-induced intestinal mucosal damage were investigated. We used a rat experimental model in which a ligated loop of the distal ileum was subjected to ischemia and reperfusion and the ensuing mucosal damage was assessed by means of lysosomal enzyme release and intestinal permeability measurements. We also determined the mucosal content of malondialdehyde, a lipid peroxidation product, and the mucosal activity of myeloperoxidase, a neutrophil granulocyte marker. Ischemia and revascularization alone caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa, and increased myeloperoxidase activity in the mucosa. Intravenous injection of enzymatic antioxidant, superoxide dismutase, together with xanthine oxidase inhibitor, allopurinol, prevented the malondialdehyde accumulation and caused attenuation of all the other effects of ischemia. Intravenous pretreatment of hydrocortisone sodium succinate (Solu-Cortef), a steroid and also a nonenzymatic antioxidant, prevented not only malondialdehyde accumulation but also neutrophil infiltration and mucosal damage. These data support a concept that neutrophil infiltration is an important element in ischemic mucosal damage. In addition, the blocking of this phenomenon may have clinical significance in attempts to modulate the potential damaging effects of the increased neutrophil infiltration associated with small-intestinal ischemia.
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PMID:Oxygen radicals, lipid peroxidation, and neutrophil infiltration after small-intestinal ischemia and reperfusion. 253 52

Impairment of lysosomal stability due to reactive oxygen species generated during the oxidation of hypoxanthine by xanthine oxidase was studied in rat liver lysosomes isolated in a discontinuous Nycodenz gradient. Production of O2.- and H2O2 during the hypoxanthine/xanthine oxidase reaction occurred for at least 5 min, while lysosomal damage, indicated by the release of N-acetyl-beta-glucosaminidase, occurred within 30 s, there being no further damage to these organelles thereafter. The extent of lysosomal enzyme release increased with increasing xanthine oxidase concentration. Superoxide dismutase and catalase did not prevent lysosomal damage during the hypoxanthine/xanthine oxidase reaction. Lysosomes reduced xanthine oxidase activity, as assessed in terms of O2 consumption, only slightly but substantially inhibited in a competitive manner the O2.- -mediated reduction of cytochrome c. This inhibition was almost completely reversed by potassium cyanide, thus pointing to the presence of a cyanide-sensitive superoxide dismutase in the lysosomal fraction. However, potassium cyanide did not affect the hypoxanthine/xanthine oxidase-mediated lysosomal damage, thus suggesting an inability of the lysosomal superoxide dismutase to protect the organelles. Negligible malondialdehyde formation was observed in the lysosomes either during the hypoxanthine/xanthine oxidase reaction or with different selective experimental approaches known to produce lipid peroxidation in other organelles such as microsomes and mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lysosomal enzyme leakage during the hypoxanthine/xanthine oxidase reaction. 256 86

The hepatotoxic effects of hyperthermic liver perfusion were investigated in male Fischer 344 rat livers. Perfusions were carried out at 37, 41, 42, 42.5, and 43 degrees C for 2 hr. During the 2 hr, the perfusate was analyzed for activity of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), N-acetyl-beta-glucosaminidase (NAG), and glutathione (GSH), oxidized glutathione (GSSG), allantoin, and potassium. After perfusion, each liver was homogenized and analyzed for total xanthine oxidase (XO) activity, percentage type-D and type-O XO, and total GSH content. Perfusate AST, LDH, NAG, and potassium levels were increased significantly with time and were significantly different in all hyperthermic perfusions from the 37 degrees C perfusion values by the end of the perfusion. Perfusate GSH + GSSG levels were increased significantly in all hyperthermic perfusions after 60 min. Liver GSH levels were significantly lowered following perfusion at hyperthermic temperatures. There was a temperature-dependent increase in the percentage of XO in the type-O form following perfusion at hyperthermic temperatures, which was strongly and positively correlated with the loss of hepatic GSH. These data support the hypothesis that hyperthermic toxicity to the liver is the result of oxidative stress brought about by conversion of XO to the type-O form.
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PMID:Effects of hyperthermia on xanthine oxidase activity and glutathione levels in the perfused rat liver. 259 31

Rat livers were perfused at 37 degrees C, 41 degrees C, 42 degrees C, 42.5 degrees C, and 43 degrees C for 2 hr. Among perfusate constituents analyzed were urea, total amino acids, N-acetyl-beta-glucosaminidase (NAG), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malonaldehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), allantoin, potassium, phosphate, and glucose. After perfusion, livers were homogenized and analyzed for xanthine oxidase (XO) activity, GSH content, and lysosomal lability. Perfusate AST, LDH, NAG, potassium, glucose, and phosphate increased significantly with time, and there were significant differences in the final values between 37 degrees C and 42 degrees C, 42.5 degrees C and 43 degrees C (P less than .05). GSH levels increased significantly at all temperatures after 90 and 120 min, whereas GSSG levels differed significantly at 60, 90, and 120 min for 37 degrees C vs. 42 degrees C, 42.5 degrees C, and 43 degrees C (P less than .05). Mean MDA levels at 37 degrees C differed from those at 41 degrees C and 43 degrees C (P less than .05) at each temperature. Allantoin levels increased significantly with time of perfusion; mean levels at 37 degrees C were significantly different from mean levels at each temperature at 60, 90, and 120 min. GSH liver tissue levels decreased with perfusion at hyperthermic temperatures; mean values at 41 degrees C, 42 degrees C, and 42.5 degrees C, and 43 degrees C differed from 37 degrees C mean values (P less than .01). Type O XO increased after 120 min perfusion from 6.4% +/- 2.0% at 37 degrees C to 55% +/- 30%, 43% +/- 27%, and 63% +/- 29% at 42 degrees C, 42.5 degrees C, and 43 degrees C, respectively. Lysosomal lability increased after perfusion at 42.5 degrees C. There was a significant increase in nonsedimentable NAG activity at 42.5 degrees C (P less than .05). These data support the premise that hyperthermic toxicity to the liver may be a consequence of oxidative stress brought about by enhanced adenosine triphosphate (ATP) consumption and conversion of XO to type O. Such conversion results in superoxide formation and subsequent depletion of cellular GSH, labilization of the lysosomes, and plasma membrane damage.
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PMID:Hyperthermic liver toxicity: a role for oxidative stress. 279 43