Immunotoxicity of butyltins in tunicates

Cima, Francesca; Ballarin, Loriano; Bressa, G.; Sabbadin, Armando

doi:10.1002/aoc.590090711

Cited by 41 publications

(28 citation statements)

References 14 publications

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“…16 22 We previously hypothesized that the severe damage to immunocytes in the presence of 10 À5 M TBT was mediated mainly by direct interaction of TBT with endogenous CaM, which, in turn, prevents the regulative activity of CaM on Ca 2 -ATPases, with a consequent diffuse, delayed, cytosolic calcium rise upon cell stimulation. 22 Altered Ca 2 homeostasis leads either to apoptosis in the case of prolonged exposure, 23 or to inhibition of the respiratory burst 17 and depolymerization of cytoskeletal components. 21 The latter effect is responsible for the remarkable changes in cell shape and loss of motility shown by TBT-treated phagocytes.…”

Section: ±11mentioning

confidence: 99%

Butyltins and calmodulin: which interaction?

Cima

Dominici

Mammi

et al. 2002

Applied Organom Chemis

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Tributyltin (TBT), widely used as an antifouling biocide, is the most abundant pesticide in coastal environments. One of its main toxic effects is immunosuppression in both vertebrates and invertebrates. At sublethal doses of TBT, phagocytes lose their ability to move towards and ingest foreign particles. For short-term cultures of haemocytes (60 min at 25 °C) of a marine invertebrate, the colonial ascidian Botryllus schlosseri, exposed to 10−5M TBT, we previously reported dose- and time-dependent impairment of yeast phagocytosis and changes in cell morphology related to cytoskeleton disorganization. These effects are Ca2+-dependent, since inactivation of Ca2+-adenosine triphosphatase and a sustained increase in cytosolic Ca2+ occurred. As TBT can antagonize the effect of chlorpromazine, a specific calmodulin (CaM) inhibitor, and the co-presence of exogenous CaM and TBT in the incubation medium resulted in the absence of effects, we hypothesized an interaction between TBT and CaM. TBT may remove endogenous CaM from cell proteins, thus inactivating them and causing alteration of Ca2+ homeostasis. With the aim of confirming the hypothesis of a direct TBT–CaM interaction, we first studied the effects of co-incubation of TBT with other exogenous proteins on restoring the ability of phagocyte morphology. Although bovine serum albumin was never able to restore cell morphology, the effect of human spectrin was similar to that described for CaM, suggesting a common non-specific mechanism of action based on the interaction of TBT with exposed hydrophobic pouches. We also analysed the conformational changes of pure CaM (10−5M) in the presence of various concentrations (10−4 to 10−3M) of TBT and its degradation products, dibutyltin (DBT) and monobutyltin (MBT), by circular dichroism. Results indicate the dose- and time-dependent interaction of TBT with CaM. This interaction is a non-covalent interaction, probably hydrophobic in nature, between the aliphatic chains of TBT and the hydrophobic regions of Ca2+-activated CaM. DBT and MBT turned out to be less active in inducing CaM conformational changes, without any significant differences between the two compounds

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Section: ±11mentioning

confidence: 99%

Butyltins and calmodulin: which interaction?

Cima

Dominici

Mammi

et al. 2002

Applied Organom Chemis

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“…Besides causing hormonal disruption, evidences that organotins seem to act upon the immune system of mammals (cetacean, rabbits, rats and sheep) (Dacasto et al, 1994a(Dacasto et al, , 1994bKannan & Falandysz, 1997; and invertebrates (mollusks and tunicates) (Cima et al, 1995;Morcillo & Porte, 1997) call for epidemiological investigations focused upon sensitive populations.…”

Section: Introductionmentioning

confidence: 99%

Occurrence of imposex in Thais haemastoma: possible evidence of environmental contamination derived from organotin compounds in Rio de Janeiro and Fortaleza, Brazil

et al. 2002

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There are indications that the widespread use of organotin compounds (TBT and TPT) as antifoulings, as stabilizers in plastic and as pesticides, has severely affected several species of marine organisms. The most striking effect of TBT and TPT as hormonal disruptors is the development of male organs in females of gastropods, currently denominated imposex. This syndrome can lead to the sterilization and death of affected organisms. The present work gives an overview of the present state of knowledge on imposex occurrence and reports results of a survey conducted in Guanabara Bay, Rio de Janeiro and in several sites along the coast of Fortaleza, Ceará State. Different stages of imposex development were verified in this survey, however, the most prominent levels appeared associated to known spot sources of TBT and TPT.

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“…This TBT concentration probably represents the threshold value of exposure around which a remarkable variability occurs following an 'all or nothing' behaviour. Therefore, 10 "M TBT was chosen for exposure of haemocytes for 1-4 h, since this concentration constantly and significantly changes cytoskeletal structure and does not cause mortality within 1 h. 9,10 In controls, both viability and apoptotic indexes, detected with Trypan Blue and Acridine Orange respectively, remained unchanged up to 4 h. For this reason, in Fig. 1 the control data are conventionally reported as time = 0.…”

Section: Resultsmentioning

confidence: 99%

“…8,25 Analogously, they are known to increase cytosolic Ca 2 in our species. 9 Noteworthy is the ATP-and calmodulindependent nuclear Ca 2 -uptake system, which appears to facilitate endonuclease activation directly during apoptosis. 26 Moreover, calmodulin plays an important role in regulating the response.…”

Section: Discussionmentioning

confidence: 99%

“…8 In previous reports we demonstrated the immunotoxicity of tributyltin (TBT) in the colonial ascidian Botryllus schlosseri, a filter-feeding marine invertebrate, inhibiting phagocytosis and the respiratory burst. 9 The effect is mediated by an extensive cytosolic calcium increase, resulting in volume loss and morphological changes related to cytoskeletal alterations. 10,11 We stress that, in contrast to the situation for vertebrates, studies on apoptosis generally induced in invertebrates by xenobiotic exposure are still greatly lacking.…”

Section: Introductionmentioning

confidence: 99%

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