Caferro Alessia, Iovine Maria Assunta, Impellitteri Federica, Faggio Caterina, Amelio Daniela, Gattuso Alfonsina, Mileti Olga, Baldino Noemi, Sperone Emilio, Cerra Maria Carmela, Imbrogno Sandra, Filice Mariacristina
Dept of Biology, Ecology and Earth Science, University of Calabria, Rende, CS, Italy.
Dept of Veterinary Sciences, University of Messina, Messina, Italy.
Environ Toxicol Pharmacol. 2025 Aug;117:104746. doi: 10.1016/j.etap.2025.104746. Epub 2025 Jun 13.
The increasing presence of antihypertensives and their metabolites in the aquatic environment is giving rise to considerable concern, due to their potential effects on non-target organisms. We here assessed whether and to what extent the exposure to Enalaprilat, the main metabolite of the Angiotensin Converting Enzyme (ACE) inhibitor Enalapril, induces morpho-functional alterations in the mussel Mytilus galloprovincialis. The effects of 10-days exposure to 7 ng/L (ET1) and 7000 ng/L (ET2) of Enalaprilat were analyzed in the digestive gland (DG) in terms of cell viability, and cell volume regulation, and in both DG and gills in terms of tissue morphology, oxidative stress and stress protein expression. Results indicated that Enalaprilat did not compromise the viability of DG cells and haemocytes, as well as the capacity of DG cells to regulate cell volume. Morphological analysis revealed an increase in eosinophilia, indicative of an inflammatory response activation, in the connective tissue of DG from ET1 group, and a loss of epithelial integrity in gills. No changes were observed in both DG and gill extracts in the relative transcript abundance of hsp70, neither in the relative protein expression, while a tissue-specific modulation of antioxidant enzymes CAT and SOD was observed in gills and DG. Overall, our data suggest that environmental exposure to Enalaprilat, by activating inflammatory and oxidative stress responses, may potentially affect animal homeostasis.
由于抗高血压药物及其代谢产物对非靶标生物可能产生影响,其在水生环境中的存在日益增加,引发了人们的广泛关注。我们在此评估了血管紧张素转换酶(ACE)抑制剂依那普利的主要代谢产物依那普利拉的暴露是否以及在何种程度上会诱导地中海贻贝形态功能发生改变。分析了在消化腺(DG)中,暴露于7纳克/升(ET1)和7000纳克/升(ET2)依那普利拉10天对细胞活力和细胞体积调节的影响,以及在消化腺和鳃中对组织形态、氧化应激和应激蛋白表达的影响。结果表明,依那普利拉不会损害消化腺细胞和血细胞的活力,也不会影响消化腺细胞调节细胞体积的能力。形态学分析显示,ET1组消化腺结缔组织中嗜酸性粒细胞增多,表明炎症反应激活,鳃上皮完整性丧失。在消化腺和鳃提取物中,hsp70的相对转录丰度和相对蛋白表达均未观察到变化,而在鳃和消化腺中观察到抗氧化酶CAT和SOD的组织特异性调节。总体而言,我们的数据表明,环境暴露于依那普利拉通过激活炎症和氧化应激反应,可能会潜在影响动物的体内平衡。