Short-term exposure to ciprofloxacin and microplastic leads to intrahepatic cholestasis, while long-term exposure decreases energy metabolism and increases the risk of obesity

Abstract

Microplastics (MPs) and antibiotics are pervasive pollutants that may pose a risk to human health. Studies have shown that both MPs and antibiotics adversely affect lipid metabolism and increase the risk of obesity. However, it remains unclear whether combined exposure to these pollutants intensify the cumulative detrimental effect on obesity and metabolism. This study demonstrated the impact of exposure to polystyrene MPs (PS, 25 nm) and ciprofloxacin (CIP), both individually and combined, for 30 d and 90 d on the hepatic metabolism of male C57BL/6J mice. The results showed that mice exposed to PS and CIP for either 30 d or 90 d exhibited lipid metabolism disorders such as increased body weight, enlarged adipocytes, triglyceride accumulation in the liver, and higher HDL-C. Differentially expressed hepatic proteins were identified via proteomic analysis. The findings indicated that exposure for 30 d caused abnormal bile acid (BA) secretion in the liver and inhibited the BA secretion pathway, which resulted in intrahepatic cholestasis. Furthermore, exposure for 90 d resolved cholestasis and reduced the overall number of differentially expressed proteins. Intestinal pathology revealed more severe damage after exposure for 30 d, while 90 d exposure decreased the adverse effect. Combined CIP and PS exposure caused damage to the organism. However, the adaptive capacity of the organism during prolonged exposure mitigated the damage caused by both, but did not imply the complete eradication of adverse effects. This study found that 90 d exposure to PS and CIP resulted in weight gain, possibly due to changes in the gut flora and suppressed energy metabolism. These results indicated that simultaneous exposure to CIP and PS exacerbated the adverse impact on the liver, causing short-term intrahepatic cholestasis. Prolonged exposure reduced the energy metabolism in the body, exhibiting varied toxicity outcomes and mechanisms at different exposure durations. This study offers novel insights into the effect of MPs and antibiotic CIP exposure on metabolic abnormalities and provides a scientific basis for assessing these risks. It also emphasizes that the adverse effect resulting from 30 d (short-term) toxic exposure may not persist and that long-term chronic toxicity needs warrants.