Swainsonine

While previous reports come mostly from the southern Americas, several outbreaks of hypersalivation in horses were observed in Middle Europe from 2016 to 2018.

To describe feed‐induced hypersalivation in European horses.

Analysis of feedstuffs.

Veterinarians and horse or stable owners were encouraged to submit feedstuffs from case outbreaks of hypersalivation in which, infectious diseases or other systemic causes of the syndrome were ruled out and intoxication was suspected. Feedstuff analysis was performed, including gross examination, microscopic analysis of fine particles, and for hay and forage mycological culturing and mycotoxin testing.

Eleven case outbreaks were investigated. Typical clinical findings in the horses were either foamy saliva around the mouth or serous salivation with puddles forming on the ground. Some horses also showed lesions of the gingival mucosa and/or the tongue. Foamy hypersalivation, sometimes combined with lesions of tongue and/or gingiva, was associated with finding of ergot sclerotia and ergot alkaloids in hay or pasture plants (ergocornin and ergocorninin having the highest concentrations). Serous hypersalivation with massive loss of fluid was associated with the fungus Rhizoctonia spp. As indicated by the detection of traces of swainsonine, mycotoxin production on the forage was seen as likely cause. The cessation of clinical signs took days to weeks after diet change, probably depending on the duration, type and amount of toxin intake.

Small number of case outbreaks, records of clinical findings and horses' management were incomplete and were reported by horse owners.

Hypersalivation due to mycotoxins in the feed has become an emerging problem for horses in middle Europe.

Swainsonine (SW), the primary toxic component of locoweed, induces toxic response in grazing livestock. The swainsonine induced toxicity is characterized by symptoms including head tremors, ataxia, and limb paralysis. The mechanisms of the toxicity remained to be investigated. The unfolded protein response (UPR) plays a key role in alleviating endoplasmic reticulum stress (ERS) by reducing protein synthesis and promoting the degradation of misfolded proteins. ERS is closely associated with both the UPR and autophagy activation. However, the involvement of the UPR signaling pathway in SW-induced ERS and autophagy remains unclear. In this study, we demonstrate that SW up-regulates the expression of GRP78, XBP1s, LC3-II/I, and ATG5 in both in vitro and in vivo models, suggesting activation of ERS, UPR, and autophagy. To investigate the molecular mechanisms by which the UPR regulates autophagy under ERS in primary rat renal tubular epithelial cells (RTECs), we observed that inhibiting PERK led to increased levels of p62. Inhibition of ATF6 significantly reduced the up-regulation of LC3-II/I, p62, and ATG5. Furthermore, inhibiting IRE1α significantly decreased the expression of LC3-II/I and p62. These findings suggest that PERK and ATF6 regulate autophagy mainly by modulating the expression of autophagy-related genes, while IRE1α likely regulates these genes through the IRE1α-XBP1 pathway. Additionally, autophagy is directly regulated through the IRE1α-JNK signaling pathway.