Submitted to: Research in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/17/2018
Publication Date: 2/19/2019
Citation: Shappell, N.W., Duke, S.E., Bartholomay, K.A. 2019. In vitro subcellular characterization of flunixin liver metabolism in heifers, steers, and cows. Research in Veterinary Science. 123:118-123. https://doi.org/10.1016/j.rvsc.2018.12.012.
DOI: https://doi.org/10.1016/j.rvsc.2018.12.012 Interpretive Summary: In the United States, our meat is inspected to ensure food safety. One aspect of a safe food supply is to ensure that drugs approved for use in livestock are found below certain levels in meat products destined for human consumption. The anti-inflammatory drug flunixin (FNX, trade name Banamine) is approved for use in cattle to treat illness, but its use must be terminated or withdrawn at a certain time prior to slaughter. This should allow for adequate breakdown of the drug, thereby achieving acceptable levels in harvested meat products. Flunixin has been detected in livers of dairy cows at concentrations exceeding allowed levels, with this occurring more often in dairy cows than in other classes of cattle. Scientists have theorized slower metabolism of FNX in sick animals or older cows, which could result in higher tissue levels, even when following prescribed withdrawal periods. For this reason, we compared FNX metabolism in liver fractions prepared from heifers, steers, and dairy cows. The rate of FNX metabolism was reduced by 40-50% in fractions from dairy cows versus heifers or steers. These findings support the theory that the presence of FNX residues in older dairy cows is related, at least in part, to slower rates of FNX metabolism. This suggests that longer withdrawal periods may be appropriate for old cows, though the effect of illness on FNX metabolism still needs further investigation.
Technical Abstract: The majority of cattle found to have violative liver residues of flunixin (FNX) in the United States are dairy cows. It has been hypothesized that illness of cows decreases the rate of FNX metabolism, resulting in violative residues at slaughter. Another contributing factor might be an age-related decrease in FNX metabolism, as dairy cull cows are typically older at slaughter than cattle raised for beef, rather than milk production. In order to investigate this possibility, subcellular fractions were prepared from liver slices from steers (6) and heifers (5) less than 30 months of age, and cows (8) greater than 48 mos of age. Cytochrome P450 (P450), NADPH-P450 reductase and glucose-6-phosphate dehydrogenase (G6PDH) activity and rate of 5-hydroxy FNX (5-OH FNX) formation were measured in liver homogenate, cytosolic, microsomal, and S9 fractions. Cows had lower concentrations of P450, NADPH-P450 reductase activity, and 5-OH FNX formation (P = 0. 02), supporting the theory that advanced age may contribute to the higher incidence of violative FNX residues in dairy cows.