Date of Graduation
Davis College of Agriculture, Natural Resources and Design
Animal and Nutritional Sciences
Diminished levels of urate have been linked to oxidative stress in birds and mammals. Urate, a major antioxidant that lowers reactive oxygen/nitrogen species (ROS/RNS), is thought to ameliorate the effects. The relationship between reduced urate, the immune system and the pathogenesis of the intestine, the liver or the brain has not been well characterized in avians. Moreover, recent studies have proposed that an increased permeability in the intestine due to some insult can induce inflammation in peripheral organs such as the brain. Allopurinol, a relatively toxic purine analogue that serves as a xanthine oxidase inhibitor, reduces urate levels which can subsequently induce an inflammation state in the intestine. For this study, White Leghorn Chickens (n=44) were divided into 11 groups, which constituted of six control groups and five allopurinol treatments fed at 15 mg/kg body weight. The dose of allopurinol was increased 5 mg/kg body weight each week for 12 weeks. Blood samples were obtained by from the brachial vein of the wing. Liver panel blood chemistries were performed to characterize the inflammations state. At the end of the study, tissues were removed after cervical dislocation and placed in liquid nitrogen. Expression levels of TNF-α, IL-6, FASLG and COX-2 were subsequently investigated in the intestines, liver and midbrain. The results showed that urate was reduced in all treatment groups regardless of time (p < 0.05), treatment groups exhibited reduced amounts of bile acids throughout time (p < 0.05) and female treatment groups exhibited increased amounts of LDH and AST from week 2 to the end of the experiment (p < 0.05). The effect of allopurinol on the intestines of females showed that expression of IL-6, COX-2, TNF-α expression increased from every other group by 185.93, 211.74 and 107.52 times respectively (p < 0.05). TNF-α expression in the liver decreased in both females and males by 3 and 2-fold respectively (p < 0.05). FASLG expression in the liver decreased 2-fold in both male and females respectively (p < 0.05). The effect of allopurinol on the midbrain of females showed that IL-6 expression decreased by 0.061fold (?) (p < 0.05) whereas in males IL-6 expression increased by almost 2-fold (p < 0.05). COX-2 expression in the midbrain increased in females and males by 7 and 10 times (p < 0.05). The midbrain of treated females reveal that the inflammatory potential was reduced in the brain tissue of female chickens due to decreased IL-6 expression. Females were found respond more intensely to allopurinol administration from an increase of intestinal permeability which could alter the laying quality and reproductive fitness. Lastly, an upregulation of IL-6 in males also induce inflammation and could be used to create a model of neuropathological disorders.
Marku, Lundrim s., "Allopurinol alters the expression of cytokines and mediators of immune cells in the systemic 2 tissue by decreasing plasma urate." (2020). Graduate Theses, Dissertations, and Problem Reports. 7724.