Immunotoxicity of pyrethroid metabolites in an in vitro model

Abstract

Risk assessment of man-made chemicals such as pesticides are mainly focused on parent compounds, and relatively little is known about their metabolites, especially with regard to target organ damages such as immunotoxicity. In the present study, the immunotoxicity of five synthetic pyrethroids (SPs) and three common metabolites was evaluated using an in vitro model by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cytoflow, and enzyme-linked immunosorbent assay (ELISA). Cell viability and apoptosis assays showed that both SPs and their metabolites possessed cytotoxicity to the monocytic cells. The aldehyde and acid derivatives were more effective than the other compounds at cytotoxicity, with inhibition of cell viability by 56.8 and 50.6% at 10⁻⁵ mol L⁻¹, and induction of 8.52 and 8.81% cell apoptosis, respectively. Exposure to SPs and their metabolites also led to changes in the secretion levels of tumor necrosis factor α (TNF α) and interleukins (ILs), and again the metabolites showed stronger effects than the parent compounds. The aldehyde derivative upregulated IL-12p70 level by 1.87-fold, and the alcohol and acid derivative increased the secretion of TNF α 5.88 and 7.96-fold, relative to the control group. In the in vitro model, the common metabolites of SPs clearly exerted greater immunotoxic effects to monocytes than the intact parent compounds. Results from the present study suggested the need for considering metabolites in achieving more comprehensive health risk assessment of man-made chemicals, including target organ toxicities such as immunotoxicity.

Perturbation of Rat Heart Plasma Membrane Fluidity Due to Metabolites of Permethrin Insecticide

“…A focal point related to mammalian risk assessment should be identified on pyrethroid metabolites, because they can be more toxic for mammals than the parent compounds [6,31]. Zhang et al [30] report that pyrethroid metabolites are cytotoxic since they can inhibit cell viability, induce apoptosis and the release of interleukins, and increase the tumor necrosis a factor more than the parent compounds. Moreover, other effects such as estrogenic activity have been demonstrated for pyrethroids and their metabolites [6,31].…”

“…Membrane fluidity of heart cells was reduced in the hydrophilichydrophobic region, while the hydrophobic interior resulted more fluid following PERM treatment [12]. Moreover, cytotoxicity and immunotoxicity of PERM have been measured in various cellular targets [23][24][25][26][27][28][29][30]. A focal point related to mammalian risk assessment should be identified on pyrethroid metabolites, because they can be more toxic for mammals than the parent compounds [6,31].…”

Prevention of cyclophosphamide-induced hemorrhagic cystitis by resveratrol: a comparative experimental study with mesna

“…Antibody specific for IL-10 was pre-coated onto a microplate. Standards and samples were pipetted into the wells, and the immobilized antibody bound any IL-10 present [31].…”

Cytokine dysregulation in autism spectrum disorders (ASD): Possible role of the environment

“…In human peripheral blood mononuclear cells, exposure to several different pyrethroid compounds suppressed both IFN-γ and IL-4 expression in a time and concentration dependent manner (Diel, Horr et al 2003). In a monocytic cell line, various synthetic pyrethroids and their metabolites reduced expression of immunoregulatory IL-10, and increased production of more inflammatory cytokines IL-12 and TNF-α (Zhang, Zhao et al 2010). In a Xenopus laevis model, application of environmentally relevant concentrations of various pyrethroids increased IL-1Β expression (Martini, Fernandez et al 2010).…”