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

Abstract

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 degrees C) for 5 d, followed by TN or 31 degrees 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.

Warmer ambient temperatures depress liver function in a mammalian herbivore

“…Laboratory rodents experienced decreases in both hepatic enzyme activity and gene expression of key biotransformation enzymes at warmer temperatures [7,8]. The underlying cause of these decreases is most probably the result of an increase in peripheral circulation under high temperatures to increase heat dissipation and protect the liver [18].…”

“…The liver is responsible for drug metabolism, and as the largest visceral organ, also plays a key role in thermoregulation [6]. Previous work in laboratory rodents has documented decreases in hepatic gene expression of xenobiotic metabolism and in hepatic enzyme activity at warmer temperatures [7,8]. Energetic processes like biotransformation may become compromised in mammals at higher temperatures as they reach their maximal capacity to dissipate body heat [9].…”

Ambient temperature‐mediated changes in hepatic gene expression of a mammalian herbivore (Neotoma lepida)

“…Temperature‐mediated shifts in hepatic gene expression were previously documented by Settivari et al. () in laboratory rats fed ergot alkaloids, that is, known fungal toxins that cause fescue toxicosis in cattle feeding on grasses infected with Neotyphodium coenophialum (Aldrich et al., ). In this study, genes associated with xenobiotic metabolism, oxidative phosphorylation and antioxidative mechanisms were downregulated in the liver after a short‐term heat shock treatment (Settivari et al., ).…”

“…Additionally, shifts in enzyme function could alter the efficiency of detoxification resulting in an overall decrease in enzymatic activity in the liver when animals are at higher ambient temperatures (Kaplanski & Ben‐Zvi, ; Pachecka, Kobylińska, Miaskiewicz, & Bicz, ). Changes at the genetic level such as differences in gene expression could also be driving the observed patterns of increased compound toxicity after short‐term exposures to warmer ambient temperatures (Settivari et al., ). These mechanisms are not mutually exclusive and could be acting in concert, ultimately resulting in reduced liver functionality and elevated compound toxicity for mammals at higher temperatures.…”

“…() in laboratory rats fed ergot alkaloids, that is, known fungal toxins that cause fescue toxicosis in cattle feeding on grasses infected with Neotyphodium coenophialum (Aldrich et al., ). In this study, genes associated with xenobiotic metabolism, oxidative phosphorylation and antioxidative mechanisms were downregulated in the liver after a short‐term heat shock treatment (Settivari et al., ). Conversely, genes associated with gluconeogenesis and apoptosis were upregulated after heat stress, demonstrating that laboratory rats were calorically stressed and experiencing hepatic tissue injury when faced with both high temperatures and foreign toxins (Guicciardi, Malhi, Mott, & Gores, ; Settivari et al., ).…”