Subchronic toxicity and hepatocyte apoptosis of dietary olaquindox in common carp (Cyprinus carpio)

Olaquindox as one of the effective antimicrobial agents and growth-promoting feed additives, had been widely used in animal and fish production. However, few studies have been done to unveil its possible toxic effect and tissue injury on aquatic animal. In this study, the toxic effect and underlying mechanisms of olaquindox toxicity were investigated in common carp when feed with different doses of olaquindox for 90 days. The morbidity and mortality, pathological changes, hematology parameters, residue concentration in the tissues of common carp were assessed, hepatocyte apoptosis was detected through ultrastructural observation and flow cytometry methods. The results showed that the morbidity and mortality increased with the increasing dosages of dietary olaquindox, subchronic exposure to olaquindox caused remarkably pathological changes, including congestion and bleeding, intramuscular edema, vacuolar degeneration, degeneration and deformation in renal tubules architecture, respiratory epithelium fusion and intestinal epithelial microvilli disintegration. Besides, dietary olaquindox led to significant changes in blood biochemical parameters including red blood cell, hemoglobin, alanine aminotransferase and aspartate aminotransferase, an elevated residue concentration of olaquindox was detected in liver and kidney after exposure, hepatocyte apoptosis and necrosis were observed. Moreover, insulin like growth factor I (IGF-I) mRNA level in liver was higher than normal level with the dose below 25 mg/kg olaquindox and was lower than normal level with the dose above 50 mg/kg. Our results demonstrated that dietary olaquindox may pose subchronic toxicity and residue in fish organs and provided scientific data for the safe application of olaquindox in fish.