Endotoxin challenge increases xanthine oxidase activity in cattle: effect of growth hormone and vitamin E treatment

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). Growth hormone (GH) and Vitamin E (E) have been shown previously to modify immune response to infection. Our objective was to determine in heifers the effect of endotoxin challenge (LPS; 3.0 microg/kg BW, i.v. bolus, Escherichia coli 055:B5) on xanthine oxidase (XO) activity in plasma and liver and the modification of this response by daily treatment with recombinant GH (0.1 mg/kg BW, i.m., for 12 days) or GH+E (E: mixed tocopherol, 1000 IU/heifer, i.m., for 5 days). In experiment 1, 16 heifers ( 348.7 +/- 6.1 kg) were assigned to control (C, daily placebo injections), GH, or GH+E treatments and were challenged with two consecutive LPS injections (LPS1 and LPS2, 48 h apart). After LPS1, plasma XO activity increased 290% (P < 0.001) at 3 h, reached peak (430%) at 24 h and returned to basal level by 48 h after LPS2. XO responses (area under the time x 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 + nitrate 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 24h 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.