ABSTRACT
Bioallethrin is a synthetic pesticide that is widely used to control insect pests. The wide use of bioallethrin has resulted in inevitable human exposure. In this study we report the effect of different concentrations of bioallethrin (10 to 200 µM, 2 h at 37 °C) on human lymphocytes under in vitro conditions. Bioallethrin treatment resulted in loss of cell viability (> 30% at 200 µM bioallethrin). Oxidative stress markers like lipid peroxidation and protein oxidation were significantly increased accompanied by lower ratio of reduced to oxidized glutathione. Enhanced ROS generation was observed through fluorescence spectroscopy and microscopy. Bioallethrin-induced oxidative stress also compromised the antioxidant defence as it reduced antioxidant capacity of cells and inhibited major antioxidant enzymes. Biomolecular modifications and systemic toxicity by bioallethrin resulted in plasma membrane damage with mitochondrial depolarization. Comet assay showed nuclear DNA fragmentation and strand scission with significant increase in tail length and olive tail moment. Apoptosis and necrosis of cells was confirmed through acridine orange/ethidium bromide dual staining and visualization under fluorescence microscope. Thus, bioallethrin causes oxidative damage and compromises the antioxidant system leading to DNA damage, cellular and organelle toxicity, resulting in apoptosis and necrosis of human lymphocytes.
Subject(s)
Allethrins/adverse effects , DNA Damage/drug effects , Lymphocytes/drug effects , Lymphocytes/metabolism , Mitochondria/drug effects , Oxidation-Reduction/drug effects , Pesticides/adverse effects , Reactive Oxygen Species/metabolism , Apoptosis/drug effects , Cell Survival/drug effects , Cells, Cultured , DNA Fragmentation/drug effects , Humans , Lipid Peroxidation/drug effects , Lymphocytes/ultrastructure , Oxidative Stress/drug effectsSubject(s)
Allethrins/adverse effects , Basophils/drug effects , Insecticides/adverse effects , Piperonyl Butoxide/adverse effects , Pyrethrins/adverse effects , T-Lymphocytes/drug effects , Adolescent , Adult , Cells, Cultured , Drug Hypersensitivity , Female , Histamine Release/drug effects , Humans , Interferon-gamma/biosynthesis , Interleukin-4/biosynthesis , Male , Middle Aged , Permethrin , Pesticide Synergists/adverse effectsABSTRACT
We have recently reported an increase in the density of muscarinic cholinergic receptors in mice neonatally exposed to a persistent environmental agent, dichlorodiphenyltrichloroethane (DDT), and a subsequent exposure as adults to nonpersistent toxicants, such as bioallethrin or paraoxon. Here we have examined the effects of an exposure like this on muscarinic receptor mRNA expression. Ten-day-old Naval Medical Research Institute mice received a single oral dose of DDT (0.5 mg/kg body weight). When aged 5 months, they received bioallethrin (0.7 mg/kg body weight per day for 7 days) or paraoxon (1.4 mg/kg body weight every second day for 7 days). mRNA expression of subtypes m1, m3, and m4 was studied in 7-month-old animals. Changes could only be discovered in the DDT-bioallethrin treated mice, where expression of subtype m4 was elevated in cortex and caudate putamen. Moreover, the expression pattern of the subtypes m1, m3, and m4 in mouse brains was found to be very similar to that seen in rats, except for slight differences in the pyramidal cell layer of the hippocampus, where the outermost part of the CA3 region did not show any m4 hybridization. The present study indicates that the earlier observed increase in muscarinic receptor density in mice exposed as neonates to DDT and as adults to bioallethrin can be attributed to changes in the expression of m4.
Subject(s)
Allethrins/adverse effects , Brain/drug effects , Insecticides/adverse effects , Paraoxon/adverse effects , RNA, Messenger/analysis , Receptors, Muscarinic/metabolism , Age Factors , Animals , Animals, Newborn , Blotting, Northern , Brain/metabolism , Environmental Exposure , In Situ Hybridization , Mice , RNA, Messenger/biosynthesis , Rats , Receptors, Muscarinic/drug effects , Receptors, Muscarinic/geneticsABSTRACT
Throughout life, mammals are exposed to environmental toxicants, some of which have acute effects on the nervous system. Early, low-dose exposure in combination with later re-exposure and possible interference with normal aging have been little studied. The present study revealed increased susceptibility in adult mice, exposed neonatally to a low dose of the insecticide bioallethrin, to renewed exposure to bioallethrin as adults. Ten-day-old Naval Medical Research Institute male mice received bioallethrin orally (0.7 mg per kg body weight per day for 7 days). When aged 5 months they were given the same dose of bioallethrin by gavage. Twenty-four hours after the last administration, a spontaneous motor activity test revealed significant aberrations in mice exposed both neonatally and as adults to bioallethrin. The density of muscarinic receptors was significantly increased. When aged 7 months, spontaneous behavioral disturbances and muscarinic receptor changes persisted and learning and memory deficits had developed. These results indicate that neonatal exposure to bioallethrin has the potential to increase susceptibility of the adult mouse to a new exposure at a dosage that does not have any effect in animals treated neonatally with vehicle.
