Dibutyltin depressed immune functions via NF‐κB, and JAK/STAT signaling pathways in zebrafish (Danio rerio)

Abstract

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-1b (IL-1b), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-a (TNF-a), interferon g2 (INFg2), nuclear factor-jB p65 (NF-kB p65), inhibitor protein-jBa (IjBa), IjB kinases b (IKKb), 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 IjB kinases a (IKKa) and IjB kinase g (IKKg) mRNA levels in the intestine and spleen. These data imply that DBT might be via suppression on IKKb/IkBa/NF-kBp65 and JAK/STAT signaling pathways to regulate the immunity of zebrafish.cytokines, dibutyltin (DBT), gene expression, immunity, zebrafish | I N TR ODU C TI ONButyltin compounds (BTs) are a group of organometallic contaminants that are used as additives of antifouling paints, biocides, and stabilizers. 1 Due to these applications, BTs enter in a diversity of aquatic systems and causing toxic effects in target and non-target organisms. [2][3][4] Tributyltin (TBT) is the most investigated of BTs because of its use in antifouling formulations and induction of imposex in gastropod. 5 The use of TBT was totally banned globally in antifouling paints from 2008. 5,6 Even with the prohibition of TBT, the polluted sediments could still be a subject of concern since TBT is relative stable and can release the degradation of dibutyltin (DBT) and monobutyltin (MBT) into water. 5,7 As a major degradation product from TBT, DBT has not been received much attention. However, DBT has been detected in surface water and drinking water at levels of 2 ppb and 53 ng/L. 8 Recently, it is reported that DBT concentrations range from below detection limits (0.38 ng Sn/L) to 23.09 ng Sn/L in the surface water of three Gorges Reservoir Region, China. 9 TBT is generally considered higher toxicity than its degradation product, DBT and MBT, however, with the exception of the immune system, where DBT might have higher toxicity than TBT. 10 It's reported that DBT resulted in a significant decrease at 100 and 200 nM of phagocytotic activity and reduced significantly phagocytic eff...

Dibutyltin Dichloride Retards Leydig Cell Developmental Regeneration in Adult Rat Testis

“…Leydig cells in the testis interstitial compartment contribute 95–99% of circulatory testosterone ( Wu et al, 2017 ). Testosterone biosynthesis is catalyzed by SCARB1, STAR, CYP11A1, 3β-HSD, CYP17A1, and 17β-HSD3 ( Wang et al, 2011 ), which gets promoted when LH binds to LHCGR on its surface ( Melsert et al, 1991 ; Foster, 1996 ; Zhang et al, 2018 ).…”

“…DBTCl can also enter the human body via food consumption, as DBTCl concentration in some fish in the market was 0.674 μg/g ( Tsunoda, 1993 ). Of the various toxicities of DBTCl, it has been reported to suppress testosterone production induced by tropic stimulation, thereby demonstrating its negative effects on Leydig cells ( Nakajima et al, 2005 ; Brown et al, 2017 ; Furukawa et al, 2017 ; Milton et al, 2017 ; Zhang et al, 2018 ). Another organotin, tributyltin chloride (TBT), has been demonstrated to block Leydig cell developmental regeneration in the adult rat testis ( Wu et al, 2017 ); therefore it is worth wondering whether DBTCl has the similar effects as both TBT and DBTCl are organotins.…”

“…Measurable levels of DBTCl has so far been found in drinking water ( Forsyth et al, 1993 ), house dust ( Fromme et al, 2005 ), foodstuffs ( Hong et al, 2002 ), and surface waters ( Bancon-Montigny et al, 2004 ). In fact, DBTCl is readily detected in human blood and liver samples ( Nielsen and Strand, 2002 ; Brown et al, 2017 ) and has been shown to cause extensive toxicities to animals, including placental and fetal toxicity, immune toxicity, and endocrine toxicity ( Brown et al, 2017 ; Furukawa et al, 2017 ; Milton et al, 2017 ; Zhang et al, 2018 ).…”

“…Leydig cell differentiation and development are regulated by endocrine system. Gonadotrophs in the pituitary gland secrete luteinizing hormone (LH, LH-β subunit is encoded by Lhb ) ( Zhang et al, 2018 ). LH promotes Leydig cell development and androgen production by directly binding to luteinizing hormone/chorionic gonadotropin receptor (LHCGR) on its surface ( Melsert et al, 1991 ), leading to an increase in steroidogenic enzyme activity, particularly steroidogenic enzyme activities of rate-limiting STAR and CYP11A1, through cAMP-PKA signaling pathway ( Foster, 1996 ).…”

“…Although comprehensive DBTCl toxicities have been demonstrated ( Brown et al, 2017 ; Furukawa et al, 2017 ; Milton et al, 2017 ; Zhang et al, 2018 ), no available studies have described the effects of DBTCl on Leydig cell development. Herein, this study aims to address the effects of DBTCl on Leydig cell developmental regeneration and the related mechanism by adopting an ethane dimethane sulfonate (EDS)-induced rat Leydig cell regeneration model.…”