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This Article Full Text Full Text (PDF) Supplemental Table 1 All Versions of this Article: jas.2008-1684v1 87/10/3142    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Settivari, R. S. Articles by Spiers, D. E. PubMed PubMed Citation Articles by Settivari, R. S. Articles by Spiers, D. E.

Effects of short-term heat stress on endophytic ergot alkaloid-induced alterations in rat hepatic gene expression¹

R. S. Settivari^*, T. J. Evans, L. P. Yarru^*, P. A. Eichen^*, P. Sutovsky^*, G. E. Rottinghaus, E. Antoniou^* and D. E. Spiers^*,2

^* Division of Animal Science, and Veterinary Diagnostic Laboratory, University of Missouri, Columbia 65211

² Corresponding author: spiersd{at}missouri.edu

Exposure to ergot alkaloids in endophyte-infected fescue (E+) is associated with impaired animal productivity, especially during heat stress, which is commonly referred to as fescue toxicosis. To elucidate the pathogenesis of this condition, the effects of short-term heat stress (HS) on hepatic gene expression in rats exposed to endophytic ergot alkaloids were evaluated. Rats implanted with telemetric transmitters to continuously measure core temperature were fed an E+ diet and maintained under thermoneutral (TN) conditions (21°C) for 5 d, followed by TN or 31°C (HS) conditions for 3 d. Feed intake (FI) and BW were monitored daily. The E+ and HS-induced alterations in hepatic genes were evaluated using DNA microarrays and PCR analyses. Hepatic antioxidant enzyme activities, as well as the incidence of apoptosis, were determined. As expected, intake of E+ reduced FI and BW from pretreatment levels under TN conditions, with greater reductions during short-term HS. Genes involved in gluconeogenesis and apoptosis were upregulated, whereas genes associated with oxidative phosphorylation, xenobiotic metabolism, antioxidative mechanisms, immune function, cellular proliferation, and chaperone activity were all downregulated with short-term HS. Hepatocytic apoptosis was increased and antioxidant enzyme activity decreased in the livers of rats exposed to HS. The hypothesized, exacerbating effects of HS on the direct, endophytic toxin-related and indirect, reduced caloric intake-associated alterations in hepatic gene expression were clearly demonstrated in rats and may help to elucidate the pathogenesis of fescue toxicosis in various animal species.

Key Words: ergot alkaloid • fescue toxicosis • heat stress • hepatic gene expression • microarray