Selection of a laboratory colony of the brown planthopper Nilaparvata lugens with the pyrethroids permethrin and λ-cyhalothrin increased its resistance to both insecticides. Biochemical analysis and synergistic studies with metabolic inhibitors indicated that elevated glutathione S-transferases (GSTs) with a predominant peroxidase activity conferred resistance to both pyrethroids, whereas esterases conferred part of the resistance to permethrin. Purified esterases hydrolysed permethrin at a slow rate, but incubation of either pyrethroid or their primary metabolites with partially purified GSTs had no effect on the metabolic profile. Although GSTs were sensitive to inhibition by both pyrethroids, they did not serve as binding proteins, as previously hypothesized [Grant and Matsumura (1988) Insect Biochem. 18, 615–622]. We demonstrate that pyrethroids, in addition to their neurotoxic effect, induce oxidative stress and lipid peroxidation in insects. Pyrethroid exposure induced lipid peroxides, protein oxidation and depleted reduced glutathione. Elevated GSTs in the resistant strains attenuated the pyrethroid-induced lipid peroxidation and reduced mortality, whereas their in vivo inhibition eliminated their protective role. We therefore hypothesize that the main role of elevated GSTs in conferring resistance in N. lugens is through protecting tissues from oxidative damage. Our study extends the GSTs' range of efficacy to pyrethroid insecticides and possibly explains the role of elevated GSTs in other pyrethroid-resistant insects.
Abbreviations used: GST, glutathione S-transferase; GPOX, glutathione peroxidase; BPH, brown planthopper; AU strain, Australian strain of BPH; SR strain, Sri Lankan strain of BPH; SRC, λ-cyhalothrin-selected SR strain; SRP, permethrin-selected SR strain; DFP, di-isopropyl fluorophosphonate; EA, ethacrynic acid; PB, piperonyl butoxide; DEF, S,S,S-tributyl phosphorothioate; ECOD, ethoxycoumarin O-de-ethylase; CDNB, 1-chloro-2,4-dinitrobenzene; DNPH, 2,4-dinitrophenylhydrazine; DDT, 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)-ethane.