The Studies On Mechanisms Of Injury Induced By Sub-Chronic Avermectin In Pigeon’s Spleen

Avermectin (AVM) is a kind of broad-spectrum antiparasitics, the use of AVM not only brings enormous benefits to humans, but also pose a threat to ecological environment. Because pigeon is widely distributed in the environment and sensitive to environmental changes, therefore, this paper investigate on the impact of AVM exposure on pigeon is very important. In this study, we use pigeon as the experimental model, the diet they fed was added different concentrations of AVM: control group fed the basal diet spiked with0mg AVM/kg diet, a low-dose group, a middle-dose group and a high-dose group fed the basal diet spiked with20,40and60mg AVM/kg diet respectively. The pigeons were euthanized after30,60and90days AVM exposure respectively. By detecting the tissue structure, oxidative damage, immune function, the expressions of heat shock proteins (Hsps) and autophagy activity to assess toxicity mechanism of AVM on pigeon spleen, this results were also conducive to more rational use of AVM and guided the treatment of AVM poisoning. The results showed that:1. AVM exposure can induce the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased, resulting in decreasing of eliminated the radicals to cause oxidative stress. Thus the contents of malondialdehyde (MDA), protein carbonyl and DNA-protein crosslinks (DPC) rates increased. These results indicated that oxidative damage occurred in spleen. And the stress damaged the lipid, proteins and nucleic acids, thus these could affect the normal physiological function of the spleen.2. AVM exposure could induce the expressions of interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α)and interleukin-4(IL-4)mRNA in pigeon spleen, but de-regulated the expressions of interferon-γ (IFN-γ) mRNA. Thesse results indicated that inflammation occurred in spleen, and immune function was inhibited.3. In the early stage of AVM exposure, the expressions of Hsps30, Hsps60, Hsps70and Hsps90were induced, whereas the expression of Hsps was inhibited by AVM exposure in the later period. These results indicated that Hsps involved in process of splenic damage.4. From detecting the expressions of autophagic genes, we could obtain that AVM exposure induced LC3, Beclin1, Dynein, ATG5, ATG4B mRNA expressions and inhibited the expressions of TORC1and TORC2mRNA. And the trend showed in a time-and dose-dependent manner. These results suggested that pigeon up-regulated the activities of autophagy to repair the damage induced by AVM exposure, but because the injury was too serious in the later stage of AVM exposure, the excessive autophagy leads to splenic cells to death. These indicated that elevated autophagy was also one of toxicity mechanism of sub-chronic AVM.In summary, this experiment showed that AVM exposure could cause oxidative stress and change the tissue morphology in the pigeon spleen, and regulated the genes of Hsps and autophagy. This study provides valuable clues regarding AVM-induced toxicology and experimental evidences.