الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 161 |  |  |
| | | from | 161 | | |
Abstract
SUMMARYUMMARY UMMARY
rganophosphorus compounds have been used as pesticides and as chemical warfare nerve agents. The mechanism of toxicity of OP is the inhibition of acetylcholinesterase, which results in accumulation of acetylcholine and the continued stimulation of acetylcholine receptors. Therefore, they are also called anticholinesterase agents. In addition to inhibition of acetyl cholinesterase enzyme, OP compounds have been shown to induce DNA damage, chromosomal aberrations and apoptosis. OP also may induce oxidative stress leading to generation of free radicals, which results in increase of oxidative destruction of lipids (lipid peroxidation) and reduction of glutathione level.
This study aims to evaluate the biomarkers of oxidative stress e.g total antioxidant capacity (TAC), malondialdhyde (MDA) to assess the effect of organophosphorus toxicity on expression of apoptosis related markers (caspase 3, capsese 9). In addition, the aim is to determine the genotoxic effects of acute organophosphorusexposure in patients before and after the appropriate treatment (atropine and oximes).
This study was conducted on 40 subjects including 30 patients admitted to the PCC-ASUH (group I) and 10 healthy volunteers (group II). Patients were of both sex in the age of 18-55 years and diagnosed as acute OP poisoning. Blood samples were withdrawn from patients of group I two times:
O
Summary
126
once on admission before treatment with atropine and oximes and the other sample was withdrawn after treatment. Also, blood samples were collected from the 10 healthy volunteer subjects of matching sex and age with group I.
For every patient, the sociodemographic data were collected. Moreover, laboratory analysis including levels of serum Na, serum K, serum pChE, ABGs, AST, ALT, TP, ALB, glucose, TAC, MDA, and activity of serum caspase3 and caspase 9, were done. In addition, comet assay and karyotyping were performed.
Results obtained from this study demonstrated that the majority of patients were intoxicated due to suicidal attempt (76.7%), while 23.3% were intoxicated accidently. Malathion was the most common organophosphorous compound caused poisoning among cases (40%) followed by diazinon (30%) and chlorpyriphos (30%). The mean age of the studied patients was 33.0± 11.7 years ranging from 18-55 years, with the majority of cases were females (53.3%), while males represented (46.7%).
OP poisoning cases before treatment showed a highly significant decrease in values of pH and HCO3- after treatment in comparison with the control group. These values increased to normal after receiving treatment. Hyperglycemia was temporary in OP poisoning cases, so that blood glucose reverted to near normal values after receiving treatment. OP poisoning cases before treatment showed hypokalemia, while
Summary
127
after treatment potassium level returned to normal level. Pseudo cholineesterase level, serum albumin and total protein showed a highly significant increase in OP poisoning cases after treatment.
The activities of caspase-3 and caspase-9 were significantly higher in cases before treatment than healthy controls, also the activity has been decreased in cases after treatment. Plasma MDA and TAC were significantly increased in OP poisoning cases before and after treatment as compared to controls and decreased after treatment with atropine and oximes.
The area under the ROC curve for caspase 3 was 0.76 with positive predictive value of 60, at cut-off point >1.95 ng/ml with sensitivity of 66.67 % and specificity of 80.95%. While the area under the ROC curve for caspase 9 was 0.72 with positive predictive value of 47.1, at cut-off point >3.8 ng/ml with sensitivity of 88.89% and specificity of 57.14%. The previous results indicate the significance of Cas3 and 9 as significant markers for prediction of mortality in OP poisoning cases.
Organophosphate poisoning cases before treatment in the current study showed significant DNA damage in the form of % tail DNA and tail length. However, OP poisoning cases showed normal karyotyping