Liver cytochrome P450 system as affected by endophyte-infected tall fescue seed extracts and ergot alkaloidsReportar como inadecuado




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Endophyte infected tall fescue E+ is the base diet for nearly all beef cattle in the southern USA. It has been linked to a variety of toxicological conditions due to the presence of large numbers of ergot alkaloids. This study was designed to investigate the effects of E+ seed extract and selected ergot alkaloids on the detoxification pathway by cytochrome P450 CYP3A4 enzyme system. Tests were performed using the P450- Glo CYP3A4 enzyme activity kit Promega, WI, according to the manufacturer’s manual. Luminescence was measured using a single tube TD20-20 luminometer. Endophyte infected tall fescue seed was extracted with 50-50 methanol-25 mM ammonium carbonate, cleaned and concentrated on Strata-X reversed phase column Phenomenex. The extracts were evaluated on an HPLC, and then tested using a serial dilution method. Commercially available ergonovine EN, ergocorine ER, bromocryptine BC and ergocryptine EC were tested individually using 0 to 44 nM concentrations. Seed extract of E+ produced a significant P < 0.05 dose dependent inhibition of CYP3A4 enzyme activity similar to that produced by the commercially available ergot alkaloids EC, ER, BC and EN which inhibited CYP3A4 enzyme activity in a significant P < 0.05 dose dependent manner with EC being most potent, followed by ER, BC, and then EN 70%, 40%, 30% and 10% at 44 nM concentration. The similarity of the inhibition curves of seed extract to that of the commercially available ergot alkaloids suggests a related mode of action and that the use of such ergot alkaloids and CYP3A4 assay is a good model to study the toxicity of tall fescue. Furthermore, it provides the foundation to identify the individual toxic components of purified endophyte infected tall fescue extract.

KEYWORDS

Seed Extract; Tall Fescue; CYP3A4; Ergot Alkaloid

Cite this paper

Moubarak, A. , Johnson, Z. and Rosenkrans Jr., C. 2012 Liver cytochrome P450 system as affected by endophyte-infected tall fescue seed extracts and ergot alkaloids. Agricultural Sciences, 3, 1-4. doi: 10.4236-as.2012.31001.





Autor: Ali S. Moubarak*, Zelpha B. Johnson, Charles F. Rosenkrans Jr.

Fuente: http://www.scirp.org/



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