RESUMO
Dibutyltin (DBT) is the degradation products of TBT, which is generally considered higher toxicity than TBT in the immune system. In order to learn more about the mechanisms of immune-toxic of DBT, we exposed zebrafish (Danio rerio) to 0, 1, 10 and 100 ng/L DBT for 8 weeks. At the end of the experiment, we determined the immune parameters and immune-related genes. The results showed that with an increase in TBT dose, lysozyme activities and IgM, C3, C4 content in intestine, skin and spleen were all significantly inhibited by the DBT exposure. Fish exposed to 10 ng/L and 100 ng/L showed significantly lower lysozyme activities and IgM, C3, C4 content than those of the control group. Zebrafish exposed to 10 ng/L and 100 ng/L DBT, the mRNA transcript levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interferon γ2 (INFγ2), nuclear factor-κB p65 (NF-kB p65), inhibitor protein-κBα (IκBα), IκB kinases ß (IKKß), Janus family of protein tyrosine kinases (JAKs) and the signal transducers and activators of transcription proteins (STATs) all increased with the DBT levels in the intestine and spleen. Those parameters showed significantly higher values in 10 ng/L and 100 ng/L than those of fish in the control group. However, no significant difference was found in IκB kinases α (IKKα) and IκB kinase γ (IKKγ) mRNA levels in the intestine and spleen. These data imply that DBT might be via suppression on IKKß/IkBa/NF-kBp65 and JAK/STAT signaling pathways to regulate the immunity of zebrafish.
Assuntos
Compostos Orgânicos de Estanho/toxicidade , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra/metabolismo , Animais , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Pele/efeitos dos fármacos , Pele/imunologia , Pele/metabolismo , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Peixe-Zebra/imunologiaRESUMO
As ubiquitous environmental toxicants, organotin (IV) compounds (OTC) accumulate in the food chain and potential effects on human health are disquieting. The present study compared the cytotoxicity of three diorganotins, namely, dimethyltin (DMT), dibutyltin (DBT) and diphenyltin (DPT), in rat pheochromocytoma (PC12) cells, and the molecular mechanisms responsible for their cytotoxic effects were also explored. Twenty-four hours exposure of PC12 cells to DBT and DPT resulted in a concentration-dependent decrease in cell viability with median lethal concentration (LC50) of 2.97 µM and 7.24 µM, respectively. However, DMT at concentrations up to 128 µM had no obvious effect on cell viability. The mechanistic study revealed that the extent of apoptosis was greater for DBT than that for DPT, followed by DMT, as evidenced by acridine orange/ethidium bromide (AO/EB) fluorescent staining method and annexin V-FITC/PI staining flow cytometry analysis, as well as generation of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP) disruption, release of cytochrome c (Cyt c), and consequent activation of caspase-9, and -3. These investigations suggested that the cytotoxic potency of three diorganotins in PC12 cells was in the order of DBT>DPTâ«DMT, and these compounds could induce PC12 cells apoptosis through ROS mediated mitochondrial pathway.