الفهرس 
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Abstract
Five replicates mitochondrial preparations from liver and kidney of each single rat was prepared to estimate the hazardous health effect related to mitochondrial dysfunction as a result of exposure to three insecticides extensively used in the Egyptian environment. Fifteen male albino rats were subjected to repeated oral sublethal dose (5, 9 and 1.9 mg / Kg bw of cypermethrin, imidacloprid and chlorpyrifos respectively, which represented 1/50 LD50) for 28 days (5 doses / week). Two of mitochondrial bioenergetics biomarker; NADH dehydrogenase (Complex I), adenosine triphosphatase (ATPase) activities and mitochondrial oxidative stress biomarkers; superoxide dismutase (SOD), glutathione Stransferase (GST) activity, lipid peroxide (MDA), protein carbonyl contents and oxidative DNA (8-OH-2DG) damage were quantified in rat urine and liver by HPLC. Deficiency occurred in the previous tested parameters as a result of the three insecticides exposure have been confirmed by histological and blue native polyacrylamide gel electrophoresis (BN- PAGE) analyses. The obtained results can be summarized as follow: Liver mitochondrial NADH dehydrogenase activities were inhibited by 56.50 %, 47.21 % and 33.58 % while, kidney mitochondrial NADH dehydrogenase activities were inhibited by 59.53%, 52.05 % and 37.23 % for cypermethrin, imidacloprid and chlorpyrifos exposed rats respectively, compared to control.Liver mitochondrial ATPase activities were inhibited by 66.17 %, 50.40 % and 55.85 % while, kidney mitochondrial ATPase activities were inhibited by 71.32 %, 50.08 % and 57.68 % for cypermethrin, imidacloprid and chlorpyrifos exposed rats respectively, compared to control. Hepatic mitochondrial SOD activities were inhibited by 59.57 %, 45.17 % and 26.85 % while, kidney mitochondrial SOD activities were inhibited by 63.25 %, 45.55 % and 19.09 % for cypermethrin, imidacloprid and chlorpyrifos exposed rats respectively, related to control.Hepatic mitochondrial GST activities were inhibited by 53.06 %, 31.21 % and 20.78 % while, kidney mitochondrial GST activities were inhibited by 61.51 %, 39.44 % and 23.59 % for cypermethrin, imidacloprid and chlorpyrifos exposed rats respectively, related to control. Mitochondrial PCC levels in liver were increase by 113.33 %, 80 % and 33.33 % whereas, mitochondrial PCC levels in kidney were increase by 144.44 %, 111.11 % and 66.66 % for cypermethrin, imidacloprid and chlorpyrifos exposed rats respectively, related to control. Mitochondrial MDA levels in liver were altitude by 101.80 %, 79.73 % and 58.55 % where, mitochondrial MDA levels in kidney were elevate by 112.16 %, 81.08 % and 50.00 % for cypermethrin, imidacloprid and chlorpyrifos exposed rats respectively, correlated to control 103 Electrophoretic resolution estimated by the BN - PAGE for resolve of (OXPHOS) membrane protein complexes solubilized from intact mitochondria, revealed that chlorpyrifos- treated animals, showed complete absence of complex I corresponding band. While a dissociated bands have been appeared lightly blue in different migration distance of complex III, IV and II. In contrast, complex V band was well distinct. Imidacloprid- treated animals showed that, the multisubunit protein complexes represented by only a distinct band of complex V and the other multiprotein complexes (I, II, III and IV) were totally missing. While, cypermethrin- treated animals its multisubunit protein complexes characterized by faint band of complex I and two light bands corresponding to complex V were recognized, one of them was showed in different migration distance as a result of cypermethrin induce dissociation. Also, a complete absence of complex, III, IV and II corresponding bands were observed. All the previous comments, reveals that a deformation in the multiprotein complexes have been made owing to the harmful effect induced by the three tested insecticides on the respiratory chain complexes. Liver histopathological examination shown that hepatic degeneration, sinusoid dilation, vacuolization and necrosis appear to be a common histopathological derangement symptom of poisoning by the three tested insecticides with different degree of severity relates to the insecticide type. However, it was observed that every insecticide appeared to have its unique symptom; hemorrhage was the most important symptoms of cypermethrin distinctive poisoning. While imidacloprid treated rats showing mild and reversible symptoms as; mild inflammatory cellular infiltration, congestion within central vein and portal triad…etc., whereas chlorpyrifos displayed deteriorating damage in a form of, destructive cholangitis. Kidney histopathological examination revealed that, exposure to cypermethrin, led to destructive effects on the kidney tissue of treated rats noting as; swelling and rupture of the glomeruli, hemorrhage in renal tubular and glomeruli, inflammatory cellular infiltration between the renal tubules, renal tubular necrosis. While imidacloprid showing degenerative damage with the appearance of disturbed tubular epithelium and dilation in urinary space, mild hemorrhage, necrotic tubular epithelia, atrophied, surrounded by inflammatory cells and congestion in the glomeruli. Also, many abnormalities in kidney section of chlorpyrifos dosed rat were detected in glomeruli and in convoluted tubules in a form of hyperchromatic mesangial cells, disturbed tubular epithelium, dilation in urinary space, hyper atrophied surrounded by inflammatory cells, proximal convoluted tubules with disturbed epithelia, necrosis and hemorrhage.The HPLC quantitative analysis displayed that the 8-OH-2DG (DNA damage oxidative biomarker) levels in liver were enhanced by 12,150%, 3,650% and 1,450%, while in kidney were raise by 201.86 %, 603.10 % and 164.59 % for cypermethrin, imidacloprid and chlorpyrifos exposed rats respectively related to control.