The effect of deoxynivalenol on serotoninergic neurotransmitter levels in pig blood 1

Abstract

Deoxynivalenol (DON) produces two characteristic toxicological effects, decreased feed consumption (anorexia) and emesis. Both effects have been linked to increased central (CNS) serotoninergic activity. Although there has also been some indication of a peripheral involvement, the role of blood pools of serotonin and related compounds in mediating DON toxicity is not well defined. In this study, the effect of DON on plasma concentrations of serotonin (5‐hydroxytryptamine, 5HT), 5HIAA (5‐hydroxyindoleacetic acid) and tryptophan (TRP), as a reflection of an induced peripheral serotoninergic system, was investigated in swine.

Typical values for the plasma concentrations of 5HT, 5HIAA, and TRP were established in pigs. Following administration of DON, either intragastrically or intravenously, concentration changes in these substances were measured over an eight hour period. The effect of low and high toxin doses were also compared.

Analyses showed no effect on plasma levels of the compounds of interest, even at sufficient toxin doses to invoke emesis in the test animals. Any variation over the course of the study remained within acceptable control limits. These results indicated no peripheral effect by DON which could account for the increased serotoninergic activity associated with altered feeding behaviour or emesis.     

Volatile sesquiterpenes from Stachybotrys chartarum: Indicators for trichothecene producing mold species?

Trichodiene, a volatile sesquiterpene which is structurally related to trichothecene mycotoxins, has been identified in the headspace of growing Stachybotrys chartarum by GC/MS. It is possible that volatile sesquiterpene patterns can be used to characterize S. chartarum and related mold isolates as trichothecene producers, thus providing clear criteria for decisions concerning the occupancy and renovation of contaminated buildings.     

A study on the effect of deoxynivalenol on serotonin receptor binding in fig brain membranes

Abstract

Central serotoninergic (5‐hydroxytryptamine, 5HT) pathways are believed to be involved in the mechanisms of anorexia and/or emesis evoked by the trichothecene mycotoxin deoxynivalenol (DON). Using an in vitro membrane receptor binding assay, the competitive potency of DON was investigated against several radioactive ligands that have a high affinity for selective 5HT‐receptor subgroups. Receptor site densities and displacement profiles in twelve selected regions of pig brain were investigated. Overall, DON possessed only minimal efficacy to competently block any of the 5HT‐ligands tested. IC₅₀ values (50% inhibitory concentration) of at least 5 mM DON were required to inhibit binding, and in certain regions concentrations of 100 mM were ineffective. In comparison, several standard 5HT‐antagonists showed 10³‐10⁵ times greater capability than DON to displace binding of these ligands. Because these results indicated DON possesses only weak affinity for the 5HT‐receptor subtypes investigated here, this suggested that in vivo, unless relatively high concentrations of the toxin are present, its pharmacological effects may be mediated by mechanisms other than a functional interaction with serotoninergic receptors at the central level.     

Effect of the appetite stimulant cyproheptadine on deoxynivalenol ‐ induced reductions in feed consumption and weight gain in the mouse 1

Abstract

Deoxynivalenol (DON, vomitoxin), a Fusarium mycotoxin, is suspected of inducing its anorectic/feed refusal activity through a serotoninergic (5HT) mechanism, possible via 5HT₂‐receptors. In this study the efficiency of cyproheptadine (CYP), a serotonin antagonist and known appetite stimulant, to attenuate the adverse effect of DON was investigated in mice. CYP was administered in the feed for two days before animals began receiving the DON, which was also added to the feed. Both agents were administered concurrently thereafter for a 12‐day period. Dosing levels included various combinations of the two compounds, ranging from 0–16 ppm DON and 0–20 ppm CYP.

Results showed that CYP could effectively offset the reduction in feed intake caused by dietary DON, but only when dose levels were optimized (CYP appeared to have a narrow effective dose range, which was also dependent on the DON concentration). In fact, optimum CYP doses were able to enhance feed intake in DON‐fed mice above control levels, indicating that more than just a direct block of the toxin's effect was occurring. Conversely though, the effect of CYP on weight gain (WG) was ambiguous. At the lower CYP doses (≤ 5 ppm), alone or in combination with the lowest DON level tested (4 ppm), a modest positive effect was noted, but at the higher DON concentrations (≥ 8 ppm) the overall WG generally remained depressed, and tended to be reduced further by increasing doses of CYP.

These results provide additional support that serotoninergic mechanisms probably play a role in mediating DON‐induced reduction in feed intake. Where and how DON actually initiates its anorectic effect, however, has not been resolved.     

真菌毒素引起的氧化应激及其毒理学意义

真菌毒素是一类由真菌产生的次生代谢产物,由于其在自然界污染的普遍性和广泛的毒性作用,被给予了充分关注。从机理上入手来研究真菌毒素毒性作用的起因具有重要意义。真菌毒素根据结构分类可达400种之多,它们的机理也各有不同,但是越来越多的研究表明真菌毒素与氧化应激有重大关联。真菌毒素引起的氧化应激能引起细胞毒性作用,还参与了其他靶点的毒性反应。同时真菌毒素能干扰细胞抗氧化系统的功能,降低细胞对毒素的抵抗能力。本文主要综述了真菌毒素中与氧化应激有密切联系的几种毒素的毒性作用,重点阐述了其与氧化应激之间的关系,以期对真菌毒素的毒性机理有更进一步的认识。