Isavuconazonium sulfate induces heart development defects in zebrafish larvae by upregulation of oxidative stress

Abstract

Environmental pollution remains a pressing global concern, with a substantial number of annual fatalities attributed to pollution-induced diseases. One emerging facet of environmental pollution is drug contamination, whereby pharmaceutical compounds can readily infiltrate water sources during manufacturing or utilization, subsequently being detected in various aquatic ecosystems. Some drugs have been detected in many watersheds at concentrations that can cause toxicity to aquatic organisms. Isavuconazonium sulfate (ISAV-SF), a prevalent antifungal medication, is no exception, warranting an exploration of its potential toxicity. However, limited research has been conducted in this domain. In this investigation, zebrafish were employed as a model organism to scrutinize the cardiotoxicity of ISAV-SF. Exposure of zebrafish embryos to concentrations of 0.5, 0.75, and 1 mg/L of ISAV-SF resulted in noteworthy cardiac developmental aberrations. These anomalies encompassed enlarged pericardial area, diminished heart rate, alterations in SV-BA distance, and the detachment of cardiomyocytes from the endocardium. Exposure to ISAV-SF caused disruption of the expression of genes related to cardiac development (gata4, klf2a, nkx2.5, vmhc, tbx2b), especially in the high concentration group. Moreover, the Notch signaling pathway was inhibited and oxidative stress levels were upregulated in all exposed groups. Remarkably, the administration of the antioxidant astaxanthin effectively mitigated oxidative stress levels, thus ameliorating heart developmental impairments. These results suggest that ISAV-SF may contribute to cardiac developmental defects by upregulating oxidative stress. This study serves as a pivotal reference for the utilization of ISAV-SF within the market, emphasizing the necessity to curtail its introduction into aquatic environments during production and consumption and to evaluate its repercussions on aquatic organisms.