Amitriptyline at an Environmentally Relevant Concentration Alters the Profile of Metabolites Beyond Monoamines in Gilt‐Head Bream

Abstract

The antidepressant amitriptyline is a widely used selective serotonin reuptake inhibitor that is found in the aquatic environment. The present study investigates alterations in the brain and the liver metabolome of gilt‐head bream (Sparus aurata) after exposure at an environmentally relevant concentration (0.2 µg/L) of amitriptyline for 7 d. Analysis of variance–simultaneous component analysis is used to identify metabolites that distinguish exposed from control animals. Overall, alterations in lipid metabolism suggest the occurrence of oxidative stress in both the brain and the liver—a common adverse effect of xenobiotics. However, alterations in the amino acid arginine are also observed. These are likely related to the nitric oxide system that is known to be associated with the mechanism of action of antidepressants. In addition, changes in asparagine and methionine levels in the brain and pantothenate, uric acid, and formylisoglutamine/N‐formimino‐L‐glutamate levels in the liver could indicate variation of amino acid metabolism in both tissues; and the perturbation of glutamate in the liver implies that the energy metabolism is also affected. These results reveal that environmentally relevant concentrations of amitriptyline perturb a fraction of the metabolome that is not typically associated with antidepressant exposure in fish. Environ Toxicol Chem 2019;00:1–13. © 2019 SETAC

Metabolomics to Study the Sublethal Effects of Diazepam and Irbesartan on Glass Eels (Anguilla Anguilla)

“…The PLS-DA model clearly differentiates the two conditions and this fact is confirmed through the corrected t-test for multiple comparisons that showed that the levels of the first two metabolites in the VIP plot (i.e., tryptophan and creatinine) are significantly (q-value = 0.081) lower in C14 (Table SI.7). The time-dependent effect was also observed in other exposure experiment set-ups carried out with fish (Ziarrusta et al, 2019), probably due to the different number of fish present in the tank along the experiment. In this case, since glass eels are fasting, we could think that the metabolism might show a kind of depletion effect in some of the metabolites.…”

“…Metabolomics is often used in toxicology to find the biochemical pathways disturbed by a stressing event (e.g., disease, nutritional imbalance, contaminant exposure…), because the search of altered small endogenous metabolites (<1.5 kDa) can provide a clear insight into the health status of an organism. In fact, environmentalmetabolomics has been successfully applied to explore the cause-effect mechanisms of CECs in aquatic organisms (Colás-Ruiz et al, 2022;Labine et al, 2022;Xu et al, 2022;Ziarrusta et al, 2019) and it is one of the key elements in adverse outcome pathways (Brockmeier et al, 2017;Dumas et al, 2022).…”

“…Therefore, as a follow-up to the previous study on the fate of CECs in glass eels, the aim of this work was to investigate the effects of diazepam and irbesartan on the glass eel metabolic system. As mentioned above, irbesartan and diazepam were selected based on the observations of previous environmental risk assessment studies (Alvarez-Mora et al, 2022), and the exposure experiments were designed taking into account both previous studies (Alvarez-Mora et al, 2022;Ziarrusta et al, 2019) and the specificities of glass eels (Figueiredo et al, 2020;Liu et al, 2019). The exposure experiments were carried out at the concentrations found in the effluent in the previous study, which would refer to the worst-case scenario (Lopez-Herguedas et al, 2021), as we do not take into account the dilution factor that may be present in the estuary.…”

Differential Serum Metabolomic Profile in Patients with Schizophrenia, Cannabis Use Disorder or Dual diagnosis

“…Since the studied cohorts were large enough, that work opened the possibility to broaden the scope and to address a more in-depth study based on non-targeted analysis to find key biomarkers beyond the ones determined through target analysis approach. For this reason, we have implemented a metabolomic approach to study the lipidic phase isolated in the previous work by means of high performance liquid chromatography coupled to high resolution mass spectrometry (HPLC-HRMS), as it has been carried out previously 23,24 . This way, a better understanding of the relation between cannabis abuse and SZ development would be achieved and potential biomarkers could be suggested.…”

Farmakokutsadura eta Garapen Iraunkorrerako 6. Helburua: ur garbia eta saneamendua

“…Adibidez, uretatik bertan dauden animalietara, elikadura-kate trofikoetan hedatzen direlarik [2]. Plentziako Itsas Estazioan urraburuekin egindako esposizio-esperimentuak frogatzen du amitriptilina (antidepresiboa), ziprofloxazinoa (antibiotikoa) eta oxibentzona (ultramore-iragazkia) arrainetan biometatzen direla, eta, horrez gain, kutsatzaile horiek arrainen plasman, burmuinean eta gibelean albo-ondorioak eragiten dituztela [7].…”