Sex-specific cardiac responses to subacute exposure to tributyltin in rats

The Lancet Commission on pollution and health reported that pollution was responsible for 9 million premature deaths in 2015, making it the world's largest environmental risk factor for disease and premature death. Among environmental pollutants, tributyltin (TBT), a biocide extensively used since the 1960s in antifouling paints, fungicides, and plastic stabilizers, is recognized as one of the most hazardous anthropogenic compounds due to its persistence and bio accumulative potential. Cardiovascular diseases are leading causes of morbidity and mortality worldwide, and exposure to environmental contaminants, like TBT, has been identified as an important risk factor. While previous studies have shown that TBT induces vascular dysfunction and increases oxidative stress and inflammation in aortic tissue, its direct effects on cardiac structure and molecular signaling remain poorly understood. Given known sex-related differences in cardiovascular physiology and disease susceptibility, this study aimed to investigate the effects of subacute TBT exposure on cardiac morphology, function and molecular pathways associated with oxidative stress and inflammation in male and female Wistar rats. Animals were randomly divided into two groups: control (C) and TBT-exposed groups (1000 ng/kg/day, for 30 days). TBT exposure increased malondialdehyde levels and disrupted antioxidant enzyme expression on both sexes, with sex-specific differences. NF-κB and IkB-α had increased protein expression in both sexes, and in males iNOS expression was also increased. In females, TBT induced morphological alterations, including reduced cardiomyocyte diameter and increased interventricular septum thickness and left atrial diameter. These findings demonstrate that subacute TBT exposure exerts cardiotoxic effects through mechanisms involving oxidative stress and inflammation, with distinct sex-specific responses.