Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/8/2003
Publication Date: 12/8/2003
Citation: Kahl, S., Elsasser, T.H. 2004. Endotoxin challenge increases xanthine oxidase activity in cattle: Effect of growth hormone and vitamin E. Domestic Animal Endocrinology. 26:315-328. Interpretive Summary: The generation of oxygen and nitrogen free radicals during infection stress is a major cause of tissue destruction. In addition, these free radicals can change the function of essential proteins and fats in the body and further debilitate animals and humans. We examined whether an enzyme called xanthine oxidase (XO) could participate in these aberrant oxidation reactions by its property of generating a highly chemically reactive oxygen radical called superoxide anion. We tested whether the stimulation of the immune system with a bacterial toxin called endotoxin would change the activity of this XO and furthermore whether other metabolic factors such as growth hormone or vitamin status would modulate the effect of endotoxin. Following the injection of endotoxin into several young female calves, both plasma and liver activity of XO increased. The plasma XO activity was augmented with treatment of calves with bovine growth hormone for 12 days prior to toxin challenge. Pretreatment of calves with vitamin E for four to five days prior to challenge significantly blunter the effects of growth hormone on plasma XO activity. Liver activity levels were affected by neither growth hormone. These data suggest that conditions that increase the production or activity of XO in an immune challenge may contribute significantly to the pool of reactants capable of generating tissue-damaging free radicals. Furthermore, these data define XO as a critical control point at which intervention strategies such as vitamin E could be directed to improve the clinical outcome of disease stress.
Technical Abstract: In addition to its basic role in the metabolism of purine nucleotides, xanthine oxidoreductase (XOR) is involved in the generation of oxygen-derived free radicals and production and metabolic fate of nitric oxide (NO). Our objective was to determine in heifers the effect of daily treatment with recombinant GH (0.1 mg/kg BW, i.m., for 12 days) and vitamin E (E, mixed tocopherol, 1000 IU/d, i.m., for 5 days) on xanthine oxidase activity in plasma and liver after endotoxin (LPS) challenge (3.0 µg/kg BW, i.v. bolus, E. coli 055:B5). In experiment 1, 16 heifers (348.7 ± 6.1 kg) were assigned to control (C, daily corn oil and saline-bicarbonate injections), GH, or GH + E treatments and were challenged with two consecutive LPS injections (LPS1 and LPS2, 48 hr apart). After LPS1, plasma XO activity increased 290% (P < 0.001) at 3 hr, reached peak (430%) at 24 hr and returned to basal level by 48 hr after LPS2. XO responses (area under the time ' activity curve, AUC) were greater after LPS1 than LPS2 (P < 0.001). Total plasma XO responses to LPS (AUC, LPS1 + LPS2) were augmented 55% (P < 0.05) over C with GH treatment but diminished to C responses in GH + E. There was a linear relationship (r2 = 0.605, P < 0.001) between total response in plasma XO activity and plasma nitrate + nitrite concentration. In experiment 2, 24 heifers (346 ± 6 kg) were assigned to C or GH treatments and liver biopsy samples were obtained at 0, 3, 6, and 24 hr after a single LPS challenge. Hepatic XO activities increased 63.3% (P < 0.05) 6 h after single LPS challenge and remained elevated at 24 h (100.1%, P < 0.01) but were not affected by GH treatment. Results indicate that LPS-induced increases in plasma XO activity could be amplified by previous GH treatment but attenuated by E administration. The data also suggest that E may be effective in controlling some mediators of immune response associated with increased production of NO via the effect on XO activity and its production of superoxide anion as well as uric acid.