الفهرس 
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Abstract
This study was carried out to evaluate the pathological and clinicopathological effects of nigella sativa oil (NSO) and resveratrol (RSV) against fipronil (FPN) toxicity in rats. Sixty apparently healthy male albino rats were divided equally and randomly into six groups (10 rats per each) and treated as follow: (1) Control group: rats were orally administered o.5 of distilled water and o.5ml olive oil daily for 45 days. (2) FPN- treated group: rats received FPN orally once daily at a dose level of 10 mg/kg BW. (3) NSO treated group: rats received NSO orally once daily at a dose of 1 ml/kg BW (4) RSV-treated group: rats received RSV orally once daily at a dose level of 20 mg/kg BW. (5) FPN+NSO- treated group: rats received oral dose of FPN (10 mg/kg BW) and NSO (1 ml/kg BW). (6) FPN+ RSV- treated group: rat received oral dose of FPN (10 mg/kg BW) and RSV (20 mg/kg BW).
The experimental treatments were conducted for 45 days. Half of rats (5 rats/group) from each group were euthanized at the end of the 30th day and the other half was euthanized at the end of the 45th day of the experiment. Serum ALT, urea and creatinine were estimated. Also, hepatic, renal and brain reduced glutathione (GSH) and malondialdhyde (MDA) were measured.
Clinically, no mortalities were recorded in control and treated groups throughout the period of the experiment. The entire treated groups showed normal growth rate throughout the period of the experiment except FPN-treated rats showed loss of appetite. In post mortem examination after one month, FPN- treated rats showed significant increase in relative testes weight. In addition, relative kidney weight significantly increased in FPN+NSO treated group as compared to control group at thirty days post- treatment. While at forty-five days post-treatment, relative liver weight showed significant increase in FPN- treated rats as compared to control group. The greatest increase was observed in FPN- treated group followed by FPN+ NSO then FPN+RSV treated groups.
The biochemical analysis revealed that serum ALT activity was significantly increased in FPN- treated group only when compared to control group at thirty days post-treatment. While at forty-five days post-treatment, the serum ALT activity significantly has increased in FPN, FPN+RSV and FPN+NSO treated groups. In addition, serum creatinine level showed significant increase in FPN-treated rats only at thirty days post-treatment. While at forty-five days post-treatment, urea and creatinine levels showed significant increase in FPN-treated rats compared to control rats.
Regarding the oxidant biomarkers, the concentration of lipid peroxidation in hepatic homogenate (expressed as MDA) showed significant increase in FPN-treated rats followed by FPN+ RSV-treated rats and finally FPN+ NSO-treated rats compared to control group, in addition, significant decrease in hepatic GSH level was observed in FPN -treated group only as compared to control at forty-five days post-treatment. However, renal MDA showed non-significant change in all treated rats as compared to control rats with significant decrease in renal GSH level in FPN-treated rats only compared to control rats at forty-five days post-treatment. Moreover, the brain tissue showed significant increase in MDA level in FPN- treated rats only compared to control rats with significant decrease in the level of renal GSH in FPN-treated followed by FPN+ NSO- treated groups at forty-five days post treatment compared to control rats.
On the other hand, histopathologic examination of liver tissue at thirty days post-treatment revealed cytoplasmic vacuolization of the hepatocytes with hepatocytic necrosis associated with mononuclear cell infiltration, and congestion in central vein. Besides, bridging necrosis and fibrosis, fatty changes and fat cyst were also detected in hepatocytes at forty-five days post-treatment in FPN-treated rats.
With regard to the histopathologic examination of kidney tissue, examination after thirty days post-treatment revealed presence of proteinaceous cast in the lumen of renal tubules, atrophied glomerulus tufts, congested glomerulus blood vessels, widened Bowman’s space, interstitial infiltration of mononuclear inflammatory cells, and edema. Besides, epitBesides, neuronal pyknosis and neuronophagia of cerebrum and wide spread hemorrhage of meninges were also recorded. Moreover, cerebellum showed hemorrhage pyknotic and hyperchromatic nuclei of Purkinje cells and depletion of granular cell layer at thirty and forty-five days post-treatment.
Moreover, the histopathologic examination of heart tissue in FPN-treated rats, at thirty days post-treatment, revealed hemorrhage and congestion of blood vessels, focal area of zenker՚s necrosis associated with mild mononuclear cell infiltration, and segmental myocytic lysis. Besides, Zenker՚s necrosis was progressed from focal to multifocal and diffuse areas at forty-five days post-treatment.
Finally, the histopathologic examination of testicular tissue at thirty days post -treatment revealed irregular and buckled basement membrane of seminiferous tubules and interstitial edema in FPN -treated rats. At forty-five days, testes of FPN-treated rats revealed sloughed germinal epithelial cells in the lumen of seminiferous tubules, giant cell formations in the lumen of seminiferous tubules and some seminiferous tubules were devoid of spermatids and spermatozoa and lined with single or double cell layer.
The co- treated groups with NSO or RSV ameliorate the toxicity induced by FPN.
Based on the these findings, it could be concluded that oral administration of FPN (10mg/kg.Bwt) to rats induced toxicity in liver, kidney, brain, testes and heart tissues as reported by the alterations in biochemical serum parameters, antioxidant and histopathological lesions. Moreover, NSO and RSV ameliorated the effect in liver, kidney, brain, testes and heart tissues against FPN-induced oxidative stress.