Determination of the cardiac damage in organophosphate poisoning and investigation of the effects of some drugs on this damage

The aim of the present study is to investigate the cardiac oxidative stress parameters and mortality in dichlorvos-induced poisoning in rats. Control group (n=8) received corn oil, dichlorvos group (n=15) received 30 mg/kg of dichlorvos, Mg group (n=10) received 200 mg/kg of MgSO4 prior to dichlorvos, atropine group (A, n=10) received 10 mg/kg atropine prior to dichlorvos, pralidoxime group (PAM, n=10) received 40 mg/kg pralidoxime prior to dichlorvos, and A-PAM group (n=10) received 10 mg/kg atropine and 40 mg/kg of pralidoxime prior to dichlorvos. All drugs and vehicle were administered by intraperitoneally and after 6h of injection, venous blood samples were collected by direct heart puncture under thiopental anesthesia. Then cardiac tissue samples were obtained. Biochemical analysis were performed to measure serum levels of cholinesterase, creatine kinase, creatine kinase-MB, cardiac troponin I, myoglobin, NT-proBNP, and NO, and to determine the tissue levels of malondialdehyde, glutathione, and NO. Histopathologically, immunohistochemical analyses were performed for apoptosis and inducible NO synthase staining in cardiac tissue. Although the serum cholinesterase level in dichlorvos group was lover than that of the control group, atropine and PAM, or combination of these pretreatments did not modify serum cholinesterase levels. However, serum cholinesterase levels were further suppressed with Mg pretreatment. Although we have demonstrated that serum NO levels in dichlorvos and Mg groups were lower than the control group, cardiac tissue NO levels in Mg group was higher than the other two groups. All the other parameters between groups were not found to be statistically significant. No marked changes in inducible NO synthase or apoptosis staining were observed. Mortality observed in dichlorvos group was 47%, and this incidence was 20% in Mg group and 0% for all the other groups (p<0.05). Serum cholinesterase levels were decreased with dichlorvos and these reductions were inhibited with atropine, pralidoxime or atropine-pralidoxime pretreatments. There was no evidence for increased oxidative stress due to dichlorvos, since malondialdehyde and glutathione levels remained unchanged. Our results do not suggest that lipid peroxidation was increased with organophosphate poisoning. In conclusion, our results implied that traditional cardiac markers, oxidative stress and NT-proBNP do not play a marked role in dichlorvos-induced poisoning and Mg therapy is not beneficial in the management of acute organophosphate poisoning.Keywords: Organophosphates, Cardiac damage, Antioxidant enzymes, Apoptosis, Nitric oxide