الفهرس 
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Abstract
The widespread use of pesticides in public health protection and agricultural programs has caused severe environmental pollution and health problems. The principle classes of compounds that are used as pesticides are organochlorines, organophosphates, carbamates, pyrethroids and various inorganic compounds. Pyrethroids are used to control a wide variety of agricultural insects, the insect vectors of disease, and to eliminate veterinary pests by topical application. Cypermethrin (CYP) is a member of the family of synthetic pyrethroids, belongs to type II class pyrethroids and is widely used in agricultural and other household applications. The generation of reactive oxygen species (ROS) has been implicated in CYP induced dysfunctions and lipid peroxidation (LPO) which are directly involved in the CYP hepatotoxicity and nephrotoxicity.
The aim of the present study was to investigate the protective effect of propolis (PRO) and curcumin (CUR) on ameliorating the histopathological, ultrastructural and biochemical changes and oxidative stress changes in the liver and kidney induced by CYP in male albino rats. Biochemical changes were evaluated by measuring liver functions (ALT, AST and ALP) and kidney function indicator (urea and creatinine), oxidative stress changes by measuring LPO, SOD and GPx activity. Hepatotoxicity and nephrotoxicity were evaluated histopathologically, histochemically and ultrastructuraly by light and electron microscopy.
The study was assessed on male albino rats each weighing 120-150 g. Forty two rats were divided into 6 groups including 7 animals per each for 28 days. 1 st group one served as control group. 2 nd group were orally received PRO (100 mg/kg/day), while 3 rd group were orally received CUR (100 mg/kg/day). 4 th group were orally received CYP (30 mg/kg/day). 5 th group were orally administrated with PRO followed by CYP, while the 6th group was treated with CUR followed by CYP.
The animals which received CYP alone showed changes in biochemical, histological, histochemical and ultrastructural alterations. CYP induced an increase in liver marker enzymes (ALT, AST and ALP) and kidney function indicators (serum urea concentration and creatinine level) at (p< 0.05). Finally, CYP resulted in an increase in lipid peroxidation and a decrease in SOD and GPx activity of liver and kidney.
Histopathological assessment of liver, after administration of CYP showed congested blood vessels, inflammatory cell infiltration, extensive vacuolar degeneration of hepatocytes, congested portal vein with thickened wall, proliferated bile ducts, hyperemic sinusoids and oedema. Also, liver tissues of CYP treated rats showed faint PAS positive reaction, depletion of protein staining reaction and marked decrease in DNA content in hepatic nuclei when compared with control group. Electron microscope examination showed nuclear changes, cytoplasmic vacuolation and damage of mitochondria of the hepatocytes. Diltation of bile duct with destructed microvilli and elongated nucleus of Kupffer cell were observed.
The microscopic examination of kidney tissues of CYP treated rats showed atrophid glomerulus, interstitial hemorrhage, dissolution in some tubules while others tubule cells displayed pyknotic nuclei, vacuolar degeneration of cells and casts in their lumen, widening of urinary space, completely demolished glomeruli, mononuclear leucocytic cells infiltration, dilated tubules and interstitial hemorrhages. CYP-treated rats showed great depletion of PAS- positive materials, depletion of protein staining reaction and marked decrease in DNA content in hepatic nuclei when compared with the control group. Renal corpuscles showed marked degeneration of almost structures of the glomeruli including podocytes with electron dense nuclei, effacement of the foot processes and thickening of the glomerular basement memberane. The proximal tubules showed irregular nuclei, multiple cytoplasmic vacuoles and short microvilli.
The biochemical, histological and ultrastructural alterations in hepatic and renal tissues were greatly ameliorated by using PRO and CUR.
In conclusion, the administration of PRO and CUR are beneficial to improve biochemical, histopathological and ultrastructural alterations in liver and kidney of rats induced by CYP due to their antioxidants effects. The present study proved that the PRO is more effective in ameliorating the histopathological, histochemical and ultrastructural changes of CYP in the liver and kidney.