Unraveling biomarkers of exposure for tenuazonic acid through urinary metabolomics.

Mycotoxins are secondary metabolites produced by fungi such as Aspergillus, Alternaria, and Penicillium, affecting nearly 80% of global food crops. Tenuazonic acid (TeA) is the major mycotoxin produced by Alternaria alternata, a prevalent pathogen affecting plants, fruits, and vegetables. TeA is notably prevalent in European diets, however, TeA biomarkers of exposure and metabolites remain unknown. This research aims to bridge this knowledge-gap by gaining insights about human TeA exposure and metabolization. Nine subjects were divided into two groups. The first group received a single bolus of TeA at the Threshold of Toxicological Concern (TTC) to investigate the presence of TeA urinary biomarkers, while the second group served as a control. Sixty-nine urinary samples were prepared and analyzed using UPLC-Xevo TQ-XS for TeA quantification and UPLC-Orbitrap Exploris for polar metabolome acquisition. TeA was rapidly excreted during the first 13 h and the fraction extracted was 0.39 ± 0.22. The polar metabolome compounds effectively discriminating the two groups were filtered using Orthogonal Partial Least Squares-Discriminant Analysis and subsequently annotated (n = 122) at confidence level 4. Finally, the urinary metabolome was compared to in silico predicted TeA metabolites. Nine metabolites, including oxidized, N-alkylated, desaturated, glucuronidated, and sulfonated forms of TeA were detected.

Widespread triazole pesticide use affects infection dynamics of a global amphibian pathogen.

The sixth mass extinction is a consequence of complex interplay between multiple stressors with negative impact on biodiversity. We here examine the interaction between two globally widespread anthropogenic drivers of amphibian declines: the fungal disease chytridiomycosis and antifungal use in agriculture. Field monitoring of 26 amphibian ponds in an agricultural landscape shows widespread occurrence of triazole fungicides in the water column throughout the amphibian breeding season, together with a negative correlation between early season application of epoxiconazole and the prevalence of chytrid infections in aquatic newts. While triazole concentrations in the ponds remained below those that inhibit growth of Batrachochytrium dendrobatidis, they bioaccumulated in the newts' skin up to tenfold, resulting in cutaneous growth-suppressing concentrations. As such, a concentration of epoxiconazole, 10 times below that needed to inhibit fungal growth, prevented chytrid infection in anuran tadpoles. The widespread presence of triazoles may thus alter chytrid dynamics in agricultural landscapes.

Impact of heavy metal exposure on biological control of a deadly amphibian pathogen by zooplankton.

Despite devastating effects on global biodiversity, efficient mitigation strategies against amphibian chytridiomycosis are lacking. Since the free-living pathogenic zoospores of Batrachochytrium dendrobatidis (Bd), the infective stage of this disease, can serve as a nutritious food source for components of zooplankton communities, these groups may act as biological control agents by eliminating zoospores from the aquatic environment. Such pathogen-predator interaction is, however, embedded in the aquatic food web structure and is therefore affected by abiotic factors interfering with these networks. Heavy metals, released from both natural and anthropogenic sources, are widespread contaminants of aquatic ecosystems and may interfere with planktonic communities and thus pathogen elimination rates. We investigated the interaction between zooplankton communities and chytridiomycosis infections in a Flemish agricultural region. Moreover, we also investigated the impact of heavy metal contamination, that was previously investigated in the region and presented in recent work, on zooplankton assemblages and chytridiomycosis infections. Finally, we tested the effect of sublethal concentrations of copper and zinc on Bd removal rates by Daphnia magna in a laboratory assay. Although zinc, copper, nickel and chromium were widely abundant pollutants, heavy metals were no driving force for zooplankton assemblages at our study locations. Moreover, our field survey did not reveal indirect effects of zooplankton assemblages on chytridiomycosis infections. However, sampling occasions testing negative for Bd showed a higher degree of copper contamination compared to positive sampling occasions, indicating a potential inhibitory effect of copper on Bd prevalence. Finally, whereas D. magna significantly reduced zoospore densities in its environment, sublethal concentrations of copper and zinc showed no interference with pathogen removal in the laboratory assay. Our results provide perspectives for further research on such a biological control strategy against chytridiomycosis by optimizing environmental conditions for pathogen predation.

Comparative population pharmacokinetics and absolute oral bioavailability of COX-2 selective inhibitors celecoxib, mavacoxib and meloxicam in cockatiels (Nymphicus hollandicus).

Selective COX-2 inhibitors are non-steroidal anti-inflammatory drugs which directly target cyclooxygenase-2 (COX-2), an enzyme mainly responsible for induction of inflammation, pyresis and pain. Although commonly used in avian medicine, limited pharmacokinetic (PK) data in domestic and companion birds are available. In this study, PK parameters and absolute oral bioavailability expressed as percentage (F%) of celecoxib (10 mg/kg BW), mavacoxib (4 mg/kg BW) and meloxicam (1 mg/kg BW) were determined following single oral (PO) and intravenous (IV) administration to cockatiels (Nymphicus hollandicus). The drugs were quantified in plasma by liquid chromatography-tandem mass spectrometry. Data were processed using the nonlinear mixed effects (NLME) approach. In contrast to celecoxib (T1/2el = 0.88 h) and meloxicam (T1/2el = 0.90 h), mavacoxib has a prolonged elimination half-life (T1/2el = 135 h) following oral administration of a commercial formulation (CF). High to complete oral absorption was observed following oral administration of celecoxib (F% = 56-110%) and mavacoxib (F% = 111-113%), CF and standard solutions, respectively. In contrast, the F% of meloxicam was low (F% = 11%). Based on the presented results, a less frequent dosing of mavacoxib is proposed compared to celecoxib and meloxicam. However, pharmacodynamic and safety studies are necessary to further investigate the use of these NSAIDs in cockatiels.