Oxidative stress and immune disturbance after long-term exposure to bisphenol A in juvenile common carp (Cyprinus carpio)

• A significant increase of Hepato somatic index, was observed in fish long-term exposed to 1000 µg/L BPA.
• Fish displayed significant oxidative stress in liver.
• Fish exposed to BPA displayed dynamic physiological response on the immune related parameters.
• A role of RXR/PPARγ pathways in fish liver in mediating the immune system response to chronic BPA exposure.

Bisphenol A (BPA) is a well-known endocrine disrupting chemical (EDC), ubiquitous in the aquatic environment, which poses an ecotoxicological risk to the health of aquatic organisms. However, the immunotoxic effects of its long-term exposure on fish have received limited attention. We examined a number of typical immune-related parameters and oxidative stress indices in the liver and blood serum of the red common carp (Cyprinus carpio), following a 30-day exposure to five different concentrations of BPA (0.1, 1, 10, 100, and 1000 μg/L). A significant increase in the hepato somatic index was observed in fish upon exposure to 1000 µg/L BPA, which correlated strongly with the accumulated BPA concentrations in fish bile. Induced oxidative stress was also apparent in the exposed fish liver, based on the enhanced levels of lipid peroxidation and inhibited activities of catalase, superoxide dismutase, and glutathione peroxidase. Serum lysozyme and C-reaction protein levels increased at low concentrations of exposure; however, they were significantly suppressed upon exposure to high concentrations. A significant increase was observed in the levels of immunoglobulin M, complement component 3, and alkaline phosphatase, in both fish liver and serum at low doses of 0.1 and 1 μg/L. This suggests that long-term exposure to environmentally relevant concentrations of BPA (even as low as 0.1 μg/L) could significantly disturb the immune response of fish. Moreover, RXRα expression in the liver was significantly altered upon BPA exposure and the trend underlying this change correlated closely with those of the most immune-related parameters, implying the involvement of the PPARγ/RXRα signaling pathway in regulating the immune response of fish upon long-term BPA exposure. In short, our results demonstrate the susceptibility of fish immune system to long-term BPA exposure. Therefore, the immunotoxicity of EDCs in aquatic organisms should not have been underestimated.