Evaluation Of Immunotoxicity Induced By Quinocetone In SD Rats Though Subacute Exposure

Quinocetone(QCT) is a new synthetic veterinary drug from the quinoxaline-l,4–dioxide (QdNOs), which invented by Lanzhou Institute of Animal Husbandry andVeterinary Drugs，Chinese Academy of Agricultural Sciences(Lanzhou，China)．QCT canimprove the intestinal flora and promote the animal growth. QCT was used for foodanimals to exert its growth promoting, improved the intestinal flora, promotes proteinabsorption and synthetic function. Considering the fact that carbadox and olaquindox haveproved mutagenicity and potential carcinogenicity, QCT got the attention of people ingradually. Recent study showed that quinocetone could cause DNA damage in HepG2cells.But the studies on the QCT induced immunocity in vivo were limited. Therefore, isnecessary to evaluate the immune system effects induced by QCT should be considered.Objectives: The objective is to evaluate the immunotoxicity of quinocetone thoughsubchronic exposure exposure in vivo, and investigate the relationship betweenimmunotoxicity and oxidative stress.Methods: Rats were divided randomly into total4groups as below:(1) high dose of QCT:2400mg/kg/day;(2) middle dose of QCT：800mg/kg/day;(3) low dose of QCT:50mg/kg/day;(4) Control group: only received the vehicle. In the28th days, body weight andsome organ like thymus，spleen weight were measured and recorded. Some of each spleenwas used for histopathological evaluation, the rest of was prepared as spleen single cellsuspensions, which were used in T/B lymphocyte proliferation test and NK cell assay. Thecomet assay was used to evaluate the DNA damage in spleen isolated cells. The ROS level, as well as GSH, and the activities of GPx, GST, SOD and CAT were measured usingcommercial assay kits.Results:(1) Compared to the solvent control group, thymus body weight ratio and spleenbody weight ratio in high dose group decreased significantly (P <0.05)。 Spleen sinuscongestion was inspected in QCT-H group at histopathological level.(2) T lymphocyte proliferation activity and B lymphocyte proliferation activity inhigh dose group decreased significantly (P <0.01), NK cell activity in high dose group andlow dose group decreased significantly (P <0.01).(3) The DNA damage was observed in all the groups treated with single QCT, theOTM value in QCT-H group and QCT-M group were significantly higher than controls.TheROS level in QCT-H group were significantly higher than controls too, it was accompaniedby decreased GSH and repression of antioxidative enzymes activity, including GPx, SODand CAT (P <0.01).Conclusion: These results demonstrate that a subchronic high dosage QCT exposure caninduce a potential immunotoxicity and DNA damage in SD rats,. The immunotoxicityinduced by QCT was mediated by oxidative stress though generating excess ROS andsuppress antioxidative systerm.