Toxicological effects of a pharmaceutical, simvastatin, in Gammarus locusta: histopathological evaluation

Abstract

Pharmaceuticals and their derivatives are considered emerging organic contaminants of aquatic ecosystems, mostly by inputs from domestic and hospital effluents. The toxicological risk associated to these substances results essentially from their ability to act on a specific metabolic process. These substances have been revealed toxic to aquatic organisms as well as to the human populations that depend on these ecosystems. However, the toxicity of pharmaceuticals in the environment is not yet well known, such as for simvastatin, which is a human drug used for the treatment of high levels of cholesterol. The amphipod Gammarus locusta is a species with high ecological relevance and high importance in toxicological studies, both acute and chronic. However, histopathological appraisals on these organisms are almost absent. Gammarus locusta (newborn) were exposed to a chronic assay with a broad range of sublethal concentrations of simvastatin. At the end of their life cycle, males and females were subjected to a histopathological evaluation using histochemical techniques for light bright-field and fluorescence microscopy, considering the hepatopancreas as the main target-organ. The comparison between the control treatment and the organisms exposed to several concentrations of the pharmaceutical permitted the selection and evaluation of qualitative and quantitative histopathological biomarkers. The results show non-monotonic dose-response curves that support the physiological alterations on the hepatopancreas epithelium reflecting alterations in the metabolism of carbohydrates, enzymatic activity and lipid storage. However, no evidence of severe lesions in this and other organs could be related to exposure. Females presented a higher ability to react to the pharmaceutical than males, when exposed to the lower concentrations of simvastatin. This can be connected with the higher energy reserves of females, associated in part to their reproductive functions. In conclusion, simvastatin affects amphipod metabolism that is responsible by alterations on cellular structures of the hepatopancreas, revealing thus more important physiological alterations than direct damage induced by the pharmaceutical.