title: The effect of allopurinol administration on mitochondrial respiration and gene expression of xanthine oxidoreductase, inducible nitric oxide synthase, and inflammatory cytokines in selected tissues of broiler chickens.
abstract: Birds have a remarkable longevity for their body size despite an increased body temperature, higher metabolic rate, and increased blood glucose concentrations compared to most mammals. As the end-product of purine degradation, uric acid (UA) is generated in the xanthine/hypoxanthine reactions catalyzed by xanthine oxidoreductase (XOR). In the first study, Cobb × Cobb broilers (n = 12; 4 weeks old) were separated into 2 treatments (n = 6); control (CON) and allopurinol (AL) 35 mg/kg BW (ALLO). The purpose of this study was to assess mitochondrial function in broiler chickens in response to potential oxidative stress generated from the administration of AL for 1 wk. There was a significant reduction in state 3 respiration (P = 0.01) and state 4 respiration (P = 0.007) in AL-treated birds compared to the controls. The purpose of the second study was to assess the effect of AL on gene expression of inflammatory cytokines interferon-γ (IFN)-γ, IL-1β, IL-6, and IL-12p35, as well as inducible nitric oxide synthase and XOR in liver tissue. Cobb × Cobb broilers were separated into two groups at 4 wk age (n = 10); CON and ALLO. After 1 wk AL treatment, half of the birds in each group (CON 1 and ALLO 1) were euthanized while the remaining birds continued on AL treatment for an additional week (CON 2 and ALLO 2). A significant increase in gene expression of XOR, IFN-γ, IL-1β, and IL-12p35 in ALLO 2 birds as compared to birds in CON 2 was detected. Liver UA content was significantly decreased in both ALLO 1(P = 0.003) and ALLO 2 (P = 0.012) birds when compared to CON 1 and CON 2, respectively. The AL reduced liver UA concentrations and increased expression of inflammatory cytokines. Additional studies are needed to determine if AL causes a direct effect on mitochondria or if mitochondrial dysfunction observed in liver mitochondria was due indirectly through increased oxidative stress or increased inflammation.
authors: Department of Animal and Nutritional Sciences, West Virginia University, Morgantown, WV 26501.
authors: T
authors: T
authors: Settle
authors: Department of Animal and Nutritional Sciences, West Virginia University, Morgantown, WV 26501.
authors: E
authors: E
authors: Falkenstein
authors: Department of Animal and Nutritional Sciences, West Virginia University, Morgantown, WV 26501 Hillar.Klandorf@mail.wvu.edu.
authors: H
authors: H
authors: Klandorf
mesh_terms: D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D030161:Avian Proteins / Q000235:genetics* / Q000378:metabolism; D002645:Chickens / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D008928:Mitochondria / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D014968:Xanthine Dehydrogenase / Q000235:genetics / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D016207:Cytokines; D004791:Enzyme Inhibitors; D000493:Allopurinol; D052247:Nitric Oxide Synthase Type II; D014968:Xanthine Dehydrogenase
keywords: allopurinol; inflammation; mitochondrial respiration; uric acid