Arsenic Trioxide Induced Neurotoxicity and Cardiotoxicity in Zebrafish (Danio rerio): Assessment of 8-hydroxy-2′deoxyguanosine Activity and Histopathological Alteration

Abstract

Arsenic trioxide is extensively utilized for its industrial, agricultural, and medicinal applications. However, its widespread use has led to significant arsenic pollution in aquatic ecosystems, raising global concerns. Despite its medicinal benefits, its effectiveness is hindered by its harmful effects on the human organ system. Therefore, this study aimed to investigate the neurotoxic and cardiotoxic effects of waterborne arsenic trioxide at concentrations of 10 ppb, 50 ppb, and 500 ppb over 90 days, using zebrafish (Danio rerio) as the animal model. Neurotoxicity and cardiotoxicity were assessed through histopathological alterations in the optic tectum and periventricular gray zone (PGZ) of the midbrain, as well as in the ventricular myocardium of the heart in adult zebrafish, serving as indicators of morphological changes. The immunoreactivity of the 8-hydroxy-2′-deoxyguanosine (8-OHdG) antibody was also assessed using an immunofluorescence assay to indicate oxidative DNA damage. The results revealed that arsenic trioxide exposure caused severe histopathological alterations, including disorganization of the optic tectum layers, clumping of mononuclear cells, pyknosis, spongiosis, and neuronal degeneration in the brain. Histopathological analysis of the heart showed structural damage to the myocardium, characterized by myofilament dissociation and infiltration of inflammatory cells between cardiomyocytes. Furthermore, immunofluorescence assays demonstrated a strong 8-hydroxy-2′-deoxyguanosine (8-OHdG) antibody reactivity in neural and cardiac tissues of arsenic trioxide-exposed groups, with a significant dose-dependent increase (P<0.05). These findings suggest that prolonged exposure to arsenic trioxide induces neurotoxicity and cardiotoxicity in zebrafish, highlighting its toxic effects on aquatic organisms and reinforcing the utility of zebrafish as a valuable model for assessing toxicity relevant to human health.