Study Of Pre-diabetes And The Mechanism In Rats Induced By Organophosphorus Pesticide Omethoate

Background：Diabetes is a severe public health problem around the world.Related epidemiological and laboratory studies indicate thatorganophosphorus pesticide exposure could increase diabetic prevalence anddeath rates. Glycosuria is increased in acute or chronic organophosphoruspesticide poisoning patients. Omethoate, one of organophosphorus pesticidewhich is more toxicity and it’s median lethal dose(LD₅₀) of feed in rats is500mg/kg, is applied extensive in many fields. The mechanism of omethoateacute poisoning is inhibition of cholinesterase activity leading to neurotoxicity.Furthermore, omethoate has toxic acion on many organizations such asdyslipidemia, oxidative stress, apoptosis, some insulin resistance effect.Currently studies of prediabetes induced by organophosphorus pesticide are inearly stage, and there are few organophosphorus pesticides tested such asmarathon, dimethoate, diazinon, dichlorvos and so on. Quantity of omethoateapplication is very large, so our study use omethoate to induce prediabetesand discuss the mechanism of prediabetes.Objective: While rats are induced by omethoate8weeks,we will examinetheir fast blood glucose（FBG） level, fast blood insulin（FINS） level, oxidativestress and insulin insulin signal transduction function to explore themechanism of prediabetes effect.Method:50wistar rats were randomly divided into5groups: Control groupwhich is dealed with nothing; Vehicle group which was provided same dose ofarachis oil as omethoate groups; L-dose group which was provided omethoateof1/40LD₅₀; M-dose group which was provided omethoate of1/20LD₅₀;H-dose group which was provided omethoate of1/10LD₅₀.After administrated8weeks, rats were killed and samples were collected. FBG level was examined by glucometer, and FINS level was examined by automaticradioimmunoassay system, and MDA level was detected with thiobarbituricacid（TBA） assay, and GSH-Px, SOD, CAT activities were measured withcolorimetry, and Bax, Bcl-2of pancreas and IRS-1, p38MAPK of skeletalmuscle were quantified with western blot. Acetylcholinesterase （AChE） andbutyrylcholinesterase（BChE） activities were examined with Ellman method.Pathology of pancreas was observed using H-E staining.Results:1. FBG, FINS level： The level of FBG was no significantdifference among five groups. There are no significant differences of FINSlevel among control group, Vehicle group, L-dose group and M-dose group.Compared with control group and Vehicle group, FINS level in H-dose groupdecreased significantly （P<0.05）.2. Blood AChE, BChE activities: These areno significant difference of blood AChE, BChE activities between control groupand Menstuum group. Compared with control group and Vehicle group, bloodAChE, BChE activities in L-dose group, M-dose group and H-dose group hadsignificantly decreased （P<0.05）, and H-dose group was the lowest.3. Bloodlipid level: Compared with control group, L-dose group and H-dose group,blood lipid level in Vehicle group and L-dose group increased significantly（P<0.05）. Compared with control group, Vehicle group and H-dose group,blood TC level was decreased significantly （P<0.05） and blood LDL level wasincreased significantly （P<0.05） in L-dose group and M-dose group. These areno significant difference of blood HDL among five groups.4. Oxidative stress inplasma, pancreas and skeleton muscle: Compared with control group andVehicle group, plasma, pancreas and muscle MDA level in L-dose group,M-dose group, H-dose group increased significantly （P<0.05）. Compared withcontrol group and Vehicle group, rats exposed to Omethoate had significantlylower plasma CAT activity （P<0.05）, but activities of CAT in pancreas andmuscle were significantly increased （P<0.05）. Compared with control group,rats exposed to Omethoate had significantly higher activities of GSH-Px in plasma and muscle （P<0.05）, but activity of GPS-Px in pancreas wassignificantly decreased （P<0.05）. Compared with control group, rats exposedto Omethoate had significantly higher activities of SOD in plasma andpancreas （P<0.05）, but activity of SOD in skeleton muscle was significantlydecreased （P<0.05）.5. Pathology of pancreas, skeletal muscle, spleen, liverand kidney in rats: Compared with control group, There are no significantdifferences of pathology in the five tissues of rats.6. Bax and Bcl-2ratio of ratspancreas: Compared with control group, Bax and Bcl-2ratio increasedsignificantly （P<0.05）, H-dose group is the highest.7. IRS-1expression of ratsskeleton muscle: Compared with control group and Vehicle group, IRS-1expression is decreased significantly （P<0.05）, H-dose group is the lowest.8.p38MAPK expression of rats skeleton muscle: Compared with control group,p38MAPK expression is increased significantly （P<0.05）, H-dose group is thehighest.Conclusion:1. AChE and BChE activities of rats induced by ometoatewere reamarkble decreased.2. Omethoate exposure to rats causes oxidative stress, dyslipidemialeading to pancreas damage.3. Omethoate exposure to rats generated pre-diabetes effect resulting inobstacle of insulin signaling pathways.