Metabonomic Study Of Biochemical Effects Of Pesticide Using ~1H NMR Spectroscopy

In the post-genomic era,new families of technologies come available to provide a comprehensive analysis of many classes of cellular molecules,such as DNAs,RNAs,proteins intermediary metabolites, etc.Termed as "-omics" these technologies have characteristics of high-through,large-scale and computer statistical analysis in methodology.Such "-omics" technologies that allow global analysis and multi-endpoint analysis are of particular importance in the field of toxicology.In the present study,Proton nuclear magnetic resonance(~1H-NMR) spectroscopy in conjunction with data reduction and pattern recognition(PR) techniques were employed to investigate metabolic profiles of urine and serum samples from the pesticide-treated and control rats to explore the biochemical effects induced by the pesticides and their mixture.Rats were administered propoxur at three doses(0.68,3.40 and 17.00 mg/kg body weight) for 28 consecutive days.The metabolic events in rat urine and serum following a 90-day oral treatment by equitoxic(1/125,1/50,1/20 LD50) doses of propoxur(0.68,1.7,and 4.25 mg/kg) and permethrin(12, 30,and 75 mg/kg) alone and in combination on male Wistar rats were also studied.The propoxur-induced changes included increase of urinary taurine,creatinine and glucose.Increased urinary lactate and acetate were only observed in the group of rats given high dose permethrin.A high concentration of urinary acetate level was observed after binary mixture of permethrin and propoxur chronic exposure.And the levels of dimethylamine,dimethylglycine and methylamine were increased after high binary mixture treatment,accompanied by decrease of urinary TCA cycle intermediates.The serum spectra from rats exposed to high dose of mixture of the two pesticides displayed increase of glucose,acetate,and lactate.These metabonomic results revealed that hepatoxici(?)y and nephrotoxicity were induced in the rats coexposed suchronicly to propoxur and permethrin to.These findings could indicate oxidative stress,mitochondrial impairment,enha(?)ced ketogenesis,fatty acidβ-oxidation in liver mitochondria,which contributed to the energy metabolism disturbance after coexpoxure to propoxur and permethrin for 90 days or subacute exposure to propoxur alone.The results of this work may provide valuable clues for understanding of the mechanisms of the impairment of pesticide,as well as show the potential power of the combination of the NMR technique and the pattern recognition method for the analysis of the biochemical effects of pesticides or pesticide mixture. This holds tremendous implication for the derivation of risk assessment guidelines for human exposure to multiple pesticides.