VARIABLES AFFECTING THE SEVERITY OF TOXICITY BY ORGANOPHOSPHORUS IN HUMAN

Abstract

Organophosphate compounds have largely been used as pesticides in many parts of the world. They are readily available because of inadequate regulations controlling their sale. This easy availability of the compounds has resulted in a gradual increase in accidental and suicidal poisoning. Many deaths occur within hours of ingestion of organophosphorus compounds like pesticides. For its prevention, speedy diagnosis and prompt treatment is required. Factors such as age, gender, route of poisoning and delay before start of treatment, may all act as prognostic risk factors, which couldpredict those poisoned cases of a poor outcome. Moreover, the bioactivation and detoxificationprocesses of OP compounds can be affected by genetic polymorphisms in biotransformation enzymes. As numerous genetic variants exist for all these enzymes. The aim of the present study was to investigate the impact of age, gender and PON1 coding region polymorphisms as factors that might affect the severity of OP poisoning. Subjects: This case-control study examined the comprehensive medical records of 50 patients, admitted to the Poisoning Control Center Ain-Shams University Hospitals, for acute OP poisoning between January 2012 and December 2012. Initial diagnoses were established in all cases based on cholinergic clinical features, the odor of OP in the gastric contents, history, and other circumstantial evidence, such as the poison or a label of an OP-containing product found by relatives. Mixed or doubtful poisoning and with co morbidities were excluded. The grouping of the OP poisoning cases was done depending upon signs and symptoms. Methods: Blood parameters studied included: measurement of cholinesterase activity PCHE, malondialdehyde (MDA), total antioxidant capacity (TAC), glucose, electrolytes, kidney functions, andlive functions.All subjects were genotyped for the PON1 gene polymorphisms; Q192R and L55M using RFLP-PCR, then genotype frequencies were compared between different OP grades. Statistical Analysis: The results were computed and statistically analyzed using SPSS statistical software version 17.0 (SPSS Inc., Chicago, IL, USA). The quantitative results were expressed as median with minimum-maximum values. The non-parametric Mann-Whitney U test and Kruskal Wallis test were used for comparing results between the groups, as appropriate. Qualitative data were presented in the form of frequencies and percentages. Differences among groups were tested using Pearson’s chi- square test (v 114 2). A P value less than 0.05 was considered statistically significant. Results & Conclusion: Levels of MDA, glucose, and HDL, were higher in patients, while the PCHE, Na, K, creatinine, triglycerides, were significantly lower compared to the control group. The remaining parameters varied in their alterations according to age, whereolder patients, of both genders, had higher significant alterations in investigated biochemical markers. Genotype frequency distribution of PON1 L55M polymorphism among different OP poisoning grades revealed no significant difference between the four grades. However, it was found that grade 4 OP poisoning had a high LM genotype frequency (3.3%), followed by MM genotype with a frequency of 33.3% and LL with a frequency of 13.3%. In contrast, frequency distribution of PON1 Q192R polymorphismshowed a highly significant (p <0.001)difference between different grades of OP poisoning, with grade 4 having a high QQ genotype frequency, followed by QR, with frequency distribution of 66.7% and 33.3%, respectively, while the RR and QR alleles were similarly distributed in grade 1 with a frequency of 50% for each.