Toxicological Effects And Mechanism Of Pesticide Lindane On Nematode Caenorhabditis Elegans

Lindane(?-HCH),one of the most important isomers of hexachlorocyclohexane,has been widely used as a highly effective organochlorine pesticide in the field of agriculture,medical and health care.Owing to its low solubility and the difficulty of degradation,lindane can enter and exist in various environmental media through volatilization,atmospheric sedimentation and surface runoff.Lindane has been found ubiquitously in the media such as atmosphere,water and soil.Moreover,residues in the environment can be transferred and accumulated into organisms and human beings because of its lipophilicity,which induces toxicity of growth,reproduction,and nervous systems.Until now,most studies about the toxic effects and mechanisms of lindane have focused on mammals and aquatic species such as mice,rabbits,tropical fish and zebrafish.However,the toxicity of lindane exposure on nematodes is practically unknown.The nematode Caenorhabditis elegans(C.elegans)is an invertebrate that lives in water and soil environments.Due to its short life cycle,ease of cultivation,and high genetic homology(60%-80%),C.elegans is an excellent model animal for laboratory toxicology researches.In this paper,C.elegans were exposed to lindane at environmentally relevant concentrations for acute,subacute and chronic exposure.The aim of this study was to investigate the toxic effects and underlying mechanisms of lindane in C.elegans.The main endpoints include three levels: physiological level(body length,locomotion behaviors,and brood size),biochemical level(intestinal damage,ROS level,lipofuscin,and cell apoptosis),and molecular level(expression of related genes).The main conclusions are as follows:(1)Acute and subacute exposure to lindane at the concentrations of 10–100 ng/L significantly reduced the body length,locomotion behaviors and brood size,which suggested that lindane exposure caused the toxic effects on the growth,nerve and reproduction in C.elegans.The results showed that locomotion behaviors were more sensitive than other endpoints in nematodes.Exposure to 1–100 ng/L of lindane significantly increased the relative fluorescence level in the intestine,indicating that lindane caused intestinal damage on nematodes.Besides,exposure to 10–100 ng/L of lindane significantly influenced ROS production and lipofuscin accumulation,suggesting that lindane induced oxidative damage.Moreover,the results showed that subacute exposure to lindane was more sensitive than acute exposure.(2)After subacute exposure,the ROS production,lipofuscin accumulation and intestinal permeability were significantly correlated with lindane-induced physiological effects by the Pearson correlation test.It suggested that intestinal damage and oxidative damage may be the main reason of lindane toxicity.Exposure to 10–100 ng/L of lindane significantly influenced the expression of intestinal development and antioxidant-related genes,especially mtm-6,opt-2,sod-5 and isp-1.Therefore,the adverse physiological effects of lindane may be induced by intestinal damage and oxidative damage,and mtm-6,opt-2,sod-5,and isp-1 genes play important roles in toxicity of lindane.(3)Chronic exposure to 0.01 ng/L of lindane significantly reduced locomotion behaviors,and the frequency of body bends was more sensitive,which suggested that chronic exposure to lindane caused significant neurotoxicity in C.elegans.After chronic exposure to lindane at concentrations of 10–100 ng/L,ROS production,lipofuscin accumulation,and cell apoptosis levels were significantly increased.Besides,ROS production,lipofuscin accumulation,and cell apoptosis were significantly correlated with lindane-induced physiological effects.Chronic exposure of 100 ng/L of lindane significantly influenced the expression of oxidative stress and apoptosis-related genes on nematodes,and sod-3,skn-1,ctl-1,efl-2,ced-13,and cep-1 genes were significantly regulated.Thus,oxidative damage and cell apoptosis caused the toxic effects of lindane,and sod-3,skn-1,ctl-1,efl-2,ced-13,and cep-1 genes paly key roles in protecting nematodes against lindane-induced toxicity.