Ecotoxicological effects of losartan on the brown mussel Perna perna and its occurrence in seawater from Santos Bay (Brazil)

Abstract

The antihypertensive losartan (LOS) has been detected in wastewater and environmental matrices, however further studies focused on assessing the ecotoxicological effects on aquatic ecosystems are necessary. Considering the intensive use of this pharmaceutical and its discharges into coastal zones, our study aimed to determine the environmental concentrations of LOS in seawater, as well as to assess the biological effects of LOS on the marine bivalve Perna perna. For this purpose, fertilization rate and embryolarval development were evaluated through standardized assays. Phase I (ethoxyresorufin O‑deethylase EROD and dibenzylfluorescein dealkylase DBF) and II (glutathione S-transferase GST) enzymes, glutathione peroxidase (GPx), Cholinesterase (ChE), lipoperoxidation (LPO) and DNA damage were used to analyze sublethal responses in gills and digestive gland of adult individuals. Lysosomal membrane stability was also assessed in hemocytes. Our results showed the occurrence of LOS in 100% of the analyzed water samples located in Santos Bay, Sao Paulo, Brazil, in a range of 0.2 ng/L-8.7 ng/L. Effects on reproductive endpoints were observed after short-term exposure to concentrations up to 75 mg/L. Biomarker responses demonstrated the induction of CYP450 like activity and GST in mussel gills exposed to 300 and 3000 ng/L of LOS, respectively. GPx activity was also increased in concentration of exposure to 3000 ng/L of LOS. Cyto-genotoxic effects were found in gills and hemocytes exposed in concentrations up to 300 ng/L. These results highlighted the concern of introducing this class of contaminants into marine environments, and pointed out the need to include antihypertensive compounds in environmental monitoring programs.

Degradation of Losartan in Fresh Urine by Sonochemical and Photochemical Advanced Oxidation Processes

“…In the aquatic environment, losartan can promote noxious effects on organisms, and it can be transformed into more toxic and persistent substances [5][6][7]. The recalcitrance to conventional treatment systems, negative environmental impact, and high excretion of losartan in urine lead to consider alternative options to eliminate this pharmaceutical from aqueous media.…”

Ecotoxicity and genotoxicity assessment of losartan after UV/H2O2 and UVC/photolysis treatments

“…The calculate CE 50/48h value of the standard LOS D. magna resulted in 331 mg L −1 (FDA 2002 ; Cortez et al 2018 ) . Also, it is noticed that among the sartan drugs, the CE 50/48h for olmesartan and valsartan was greater than 120 mg L −1 and 580 mg L −1 , respectively, showing high acute toxicity for these class of compounds (Bayer et al 2014 ).…”

“…However, there are very few reports on the genotoxic effect of LOS at environmentally relevant concentrations. Cortez et al ( 2018 ) observed DNA damage in mussel Perna perna gills cells after exposure to LOS at 3000 ng L −1 . Still, the evaluation of the genotoxicity of environmental contaminants remains little explored in the risk assessment.…”

“…Several sources of pharmaceutics in the environment have been reported, including wastewater treatment plants (WWTPs), landfills, hospitals effluents, and pharmaceutical manufacturing facilities (PMFs) (Scott et al 2018 ). LOS has been detected in several environmental matrices, usually in the range of ng L −1 to ug L −1 (Kot-Wasik et al 2016 ; Botero-Coy et al 2018 ; Cortez et al 2018 ; Wang et al 2018 ; Castiglioni et al 2020 ; Golovko et al 2020 ). However, Larsson et al ( 2007 ) detected LOS in extremely higher concentrations (2.4-2.5 mg L −1 ) in an effluent from a pharmaceutical manufacturing facility.…”

“…Since LOS is present in the environment, it is crucial to investigate its toxic effects on non-target organisms, especially chronic ones. Previous studies have reported toxic effects of LOS to different organisms, such as microcrustaceans, fish and microalgae (FDA 2002 ), macrophytes (Godoy et al 2015 ), and marine invertebrates (Yamamoto et al 2014 ; Cortez et al 2018 ). However, studies that evaluate sublethal effects of LOS are still scarce.…”