Mammalian Immunoassays for Predicting the Toxicity of Malathion in a Laboratory Fish Model

Abstract

This study describes the use of a panel of immune assays, originally developed by the National Toxicology Program for assessing xenobiotic-induced immunotoxicity in mice, to quantify the effects of sublethal malathion exposure on the immune responses of fish. For this study, Japanese medaka (Oryzias latipes) were exposed subchronically to the organophosphate pesticide malathion in a series of two experiments. In the first set of studies, fish were exposed for 7 or 14 d to untreated well water (i.e., controls) or to waterborne malathion at 0.2 or 0.8 mg/L. Following exposure, fish from each group were sacrificed and their kidneys (primary organ of leukopoiesis in fish and equivalent to mammalian bone marrow) were used to provide cells for assessing any malathion-induced effects upon nonspecific and acquired immune defense mechanisms. Effects upon humoral-mediated immunity were determined by enumerating antibody plaque-forming cell (PFC) numbers from a subset of fish exposed to malathion for 14 d and then injected intraperitoneally (ip) with sheep erythrocytes (sRBC). Results of these studies demonstrated that while malathion exposure had no significant effect upon hematocrit/leukocrit values or upon mitogen-stimulated T-cell lymphoproliferation, PFC numbers in the kidney of exposed fish were significantly reduced (compared to control fish) in a dose-dependent manner. In addition, total recoverable kidney cell numbers and viability, as well as superoxide anion production by kidney phagocytes, were reduced slightly (compared to control values) in fish exposed for 14 d to the highest malathion concentration tested. In the second set of experiments, medaka exposed for up to 21 d to either 0.1 or 0.3 mg malathion/L were challenged ip with an LD50 dose of the bacterial fish pathogen Yersinia ruckeri. Results from these infectivity studies demonstrated that exposure to either malathion concentration, for 14 or 21 d reduced host resistance against Yersinia infection. Taken together, these findings demonstrate the applicability of mammalian immune assays for predicting malathion-induced immunosuppression in a teleost fish, as well as the potential utility of a small laboratory fish to serve as an alternate model for mammals in immunotoxicological studies.

Nephrotic syndrome and acute kidney injury induced by malathion toxicity

“…There are many animal studies showing the toxic effect of malathion on the kidney due to oxidative stress and negative alterations on antioxidant enzyme activities,12–20 leading to reduced total kidney cell numbers,21 histological and functional impairment of renal tubules,22–25 glomerular inflammation26 and proteinuria 25 26…”

Immunotoxicity of acute acephate exposure in control or IL‐1‐challenged rats: correlation between the immune cell composition and corticosteroid concentration in blood

“…6 -8 (ii) Malathion reduced host resistance against Yersinia infection in fish, 9 attenuated antigen-induced antibody response 9 and suppressed splenic plaqueforming cells in mice and rats. 10 However, some studies have shown that malathion either caused immunopotentiation or did not affect immunity in rats.…”

Histopathologic changes in the kidney tissue of Prochilodus lineatus Valenciennes, 1836 (Characiformes, Prochilodontidae) induced by sublethal concentration of Trichlorfon exposure

“…Many times the recommended therapy in the parasite infestation combat is based on chemical products use, especially the organo-phosphates (Rao & Dad, 1979). However, it is known that the organophosphate used for the disease treatments can also cause histopathologic changes in many fish organs but studies in this area are still in an incipient phase (Ram et al, 1989;Hamm et al, 1998;Beaman et al, 1999). The aim of this bioassay was to investigate the histopathologic changes on the kidney of Prochilodus lineatus exposed to a high Dipterex 500 (Trichlorfon) concentration.…”