الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
In recent years, substantial efforts have been made to identify efficient natural products with limited side effects. Plants used in folk medicine to treat the toxicity of insecticides represent a viable alternative for the control of this toxicity. The search is still generally focused on identification and isolation of natural products to be used in the treatment of toxicity of organophosphate (chlorpyrifos) and carbamate (methomyl) insecticides. Thus, the present study was designed to evaluate the preventive effect of S. officinalis and R. graveolens ethanolic extracts on chlorpyrifos- and methomyl-induced hepatotoxicity, nephrotoxicity, testicular toxicity and cardiotoxicity in experimental rats. Animals were divided in to seven groups: group 1 (normal):Each animal was orally given the equivalent volume of 1% CMC (as vehicle), six days per week by oral gavage based on body weight (5ml/kg b. w.). group 2 (chlorpyrifos-administered group):The rats in this group wereadministeredchlorpyrifos at a dose level of 13.8 mg/kg b. w. 2 times/week and the equivalent volume of 1% CMC 6 times/week by oral gavage for 4 weeks. group 3 (chlorpyrifos-administered group treated with S. officinalis leaf ethanolic extract):The rats in this group wereadministered ethanolic extract of S. officinalis leaves 6 days/weekby oral gavage at dose level of 50mg/kg b. w./day along with chlorpyrifosoral administration. group 4 (chlorpyrifos-administered group treated with R. graveolensleaf ethanolic extract):The rats in this group wereadministered ethanolic extract of R. graveolensleaves6 days/weekby oral gavage at dose level of 50mg/kg b. w./day along with chlorpyrifosoral administration. group 5 (methomyl-administered group):The rats in this group wereadministeredmethomyl at a dose level of 1.6 mg/kg b. w. 2 times/week and the equivalent volume of 1% CMC 6 times/week by oral gavage for 4 weeks. group 6 (methomyl-administered group treated with S. officinalisleaf ethanolic extract):The rats in this group wereadministered ethanolic extract ofS. officinalis leaves 6 days/week by oral gavage at dose level of 50mg/kg b. w./day along with methomyloral administration. group 7 (methomyl-administered group treated with R. graveolensleaf ethanolic extract):The rats in this group wereadministered ethanolic extract of R. graveolensleaves6 days/week by oral gavage at dose level of 50mg/kg b. w./day along with methomyloral administration. Both chlorpyrifos- and methomyl-administered groups are compared with normal ones and chlorpyrifos- and methomyl-administered groupstreated with S. officinalis and R. graveolens ethanolic extractsare compared with chlorpyrifos- and methomyl-administered control groups. Results showed that chlorpyrifos and methomyl caused a marked elevation in serum enzymes (ALT, AST and LDH) activities and total bilirubin level together with a significant decrease in serum levels of total protein and albumin. Concomitant with these biochemical changes, remarkable histopathological alterations in liver tissue were observed in chlorpyrifos- and methomyl-administered animals, which exhibited inflammatory cells infiltrations, necrosis, apoposis of hepatocytes, fatty changes,haemorrhage and congestion of the portal vein. The treatment of these animals with R. graveolensand S. officinalisethanolic extracts, successfully prevented most of these biochemical and histological alterations. Both chlorpyrifosand methomyl administration produced a highly significant elevation ofmRNA expression ofNF-κB, IL-1β, P53and COX-2while produced a highly significant decrease onmRNA expressionof Bcl-2as compared with normal rats. The treatment withS. officinalisand R. graveolens ethanolic extracts to bothchlorpyrifos- and methomyl-administered rats induced a highly significant amelioration of the elevated mRNA expressionof the detected genes as compared with the corresponding controls.Moreover, thetreatment withS. officinalis and R. graveolens ethanolic extractsto bothchlorpyrifos- and methomyl-administered rats induced a highly significant increasein mRNA expressionof Bcl-2. Concerning oxidative stress and antioxidant defense system, the elevated liver lipid peroxidation (LPO) of chlorpyrifos- and methomyl-administered rats, was significantly decreased as a result of the two tested treatments. The depleted hepatic glutathione content (GSH) as well as the decreased hepatic glutathione-S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities of chlorpyrifos- and methomyl-administered rats were potentially increased as a result of the treatments. The chlorpyrifos- and methomyl-induced nephrotoxicity was evidenced by elevations in serum biochemical variables related to kidney dysfunction including creatinine, urea and uric acid levels as well as histopathological changes like congestion of glomeruler tufts, inflammatory cells infiltration, renal haemorrhage. The treatment of chlorpyrifos- and methomyl-administered rats with S. officinalis and R. graveolens ethanolic extracts decreased the elevated levels of serum creatinine, urea and uric acid that were induced by chlorpyrifos- and methomyl-administration. In addition to biochemical improvement, the histological deteriorations of the kidney were ameliorated in the case of the both treatments. Concerning oxidative stress and antioxidant defense system, the elevated kidney LPO of chlorpyrifos- and methomyl-administered rats was significantly decreased as a result of S. officinalis and R. graveolens treatments. The depleted kidney GSH content was significantly increased in the case of S. officinalisand R. graveolens treatments. Moreover, the decreased activities of kidney GST,GPx and SOD activities was significantly improved as a result of the treatments. Results also showed that chlorpyrifos and methomyl caused a marked decrease in serum sexual hormones testosterone, LH and FSH levels. Concomitant with this biochemical change, remarkable histopathological alterations in testes tissue were observed in chlorpyrifos- and methomyl-administered animals. The treatment of these animals with S. officinalisand R. graveolensethanolic extracts, successfully prevented most of these biochemical and histological alterations. Concerning oxidative stress and antioxidant defense system, the elevated testesLPO of chlorpyrifos- and methomyl-administered rats, was significantly decreased as a result of the two tested treatments. The depleted GSH content in the testes as well as the decreased GST,GPx and SOD activities in the testes of chlorpyrifos- and methomyl-administered rats were potentially increased as a result of the treatments. Finally, the chlorpyrifos- and methomyl-induced cardiotoxicity was evidenced by elevations in serum CK-MB, AST and LDH activities as well as histopathological changes. The treatment of chlorpyrifos and methomyl-administered rats with S. officinalis and R. graveolens decreased the elevated levels of serum CK-MB AST and LDH activities induced by chlorpyrifos- and methomyl-administration. In addition to biochemical improvement, the histological deteriorations of the heart were ameliorated in the case of the both treatments. Regarding oxidative stress and antioxidant defense system, the elevated heart LPO of chlorpyrifos- and methomyl-administered rats was significantly decreased as a result of S. officinalis and R. graveolens treatments. The depleted heart GSH content was significantly increased in the case of S. officinalis and R. graveolens treatments. Moreover, the decreased activities of heart GST,GPx and SOD activities were significantly improved as a result of the treatments. In conclusion, chlorpyrifos and methomyl toxicities increases the formation of oxygen free radicals, reduces antioxidants and increases LPO which lead to organ damage. S. officinalis and R. graveolens have potential chemopreventive effects against chlorpyrifos- and methomyl-induced hepatotoxicity, nephrotoxicity, testicular toxicity and cardiotoxicity. These ameliorative chemopreventive effects may be mediated via improving the anti-oxidant defense system, anti-inflammatory as well as anti-aptotic actions.