Effects of maduramicin on adult zebrafish (Danio rerio): Acute toxicity, tissue damage and oxidative stress.

Maduramicin, a potent polyether ionophore antibiotic, has been widely used to control coccidiosis in the poultry production. Nevertheless, incomplete metabolism of maduramicin in chicken may result in its accumulation in the aquatic environment, while maduramicin's threat to fish remains largely unknown. In the present study, we focused on acute toxicity, histopathological lesion and oxidative stress damage of maduramicin in adult zebrafish. Primarily, we obtained that the 96-h median lethal concentration (96 h LC50) of adult zebrafish exposure to maduramicin was 13.568 mg/L. On basis of that, adult zebrafish were separately exposed to 0.1 mg/L (1/125 LC50), 0.5 mg/L (1/25 LC50) and 2.5 mg/L (1/5 LC50) maduramicin for 14 days. On day 3, 0.1 mg/L maduramicin significantly increased the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione s-transferase (GST) in the liver of zebrafish, while the activities of these antioxidant enzymes in the liver were significantly inhibited by 2.5 mg/L maduramicin. Moreover, the contents of malondialdehyde (MDA) in the liver of different dose groups were all significantly promoted after 14 days of exposure. For the gill of zebrafish, the increase in MDA contents was found after only 3 days of exposure to maduramicin. Furthermore, maduramicin treatment significantly up-regulated the mRNA levels of genes (sod1, gpx1a, gstr, nrf2 and keap1) in the liver of zebrafish after 3 days of exposure. On days 6, 9 and 14, maduramicin treatment significantly down-regulated the mRNA levels of these genes in the liver of zebrafish. Meanwhile, maduramicin significantly down-regulated the mRNA levels of genes (sod1, cat, gpx1a, gstr, nrf2 and keap1) in the gill of zebrafish during the 14-day of exposure. In addition, a dose-dependent induction in histopathological lesion was observed in multiple organs after 14 days of exposure, including lamellar fusion, epithelial lifting in the gill and vacuole formation in the liver as well as the fracture of intestinal villus in the intestine. Taken together, our findings demonstrated that waterborne maduramicin (2.5 mg/L) exposure can induce severe oxidative stress and tissue damage in adult zebrafish while this damage was not enough to kill them after 14 days of waterborne exposure.