الفهرس 
INTRODUCTIO AND AIM OF THE WORKOnly 14 pages are availabe for public view
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Abstract
Cadmium (Cd) is known to be one of the most toxic environmental and industrial pollutants. Its industrial applications were based on its unique chemical and physical properties. It is one of the most harmful heavy metals and it is able to induce severe injury. There is considerable evidence suggesting that the kidney is a critical organ affected by Cd poisoning since the pathological changes are primarily observed in this organ.
This study was concerned with the description of light and electron microscopic structural changes in the rat kidney cortex following cadmium chloride [Cd(Cl)2] administration. This present research was a trial to find out a protective measure that can help the people who exposed to this toxic substance. Nigella sativa oil (NSO) which is known as an antioxidant was used concomitantly with Cd(Cl)2 to make sure if or not it has a nephron-protective effect.
Fifty six adult male albino rats (weighting about 150-200 g) were divided into four groups. Group one; the control group, received a subcutaneous dose of isotonic Na Cl (2ml/ kg/day) throughout the experiment. Treated animals were divided into three groups; group two (one week exposure); group three (two weeks exposure) and group four (four weeks exposure). Each one of the treated groups was subdivided into two subgroups, one of them received Cd(Cl)2 subcutaneously in a dose of 0. 49 mg/kg/day while the other was given Cd(Cl)2 (in the same dose) combined with an oral dose of NSO (2 ml /kg/d ). Rats were sacrificed at the end of 1st, 2nd and 4th week from the initiation of the experiment. Kidneys were removed immediately, fixed and processed for histological, immunocytochemical and ultra-structural studies.
In the present study, there was an increase in plasma levels of urea and creatinine (one week exposure) which was more marked on 2 weeks exposure to Cd(Cl)2. Concomitant administration of NSO and Cd(Cl)2 led to a significant decreased in these levels.
This work showed various morphological changes in the renal cortex after Cd(Cl)2 exposure. These changes were more obvious and widespread by increasing the duration of exposure.
These morphological changes were in the form of; peri-tubular capillary dilatation, interstitial hemorrhages, swollen or shrinked renal glomeruli, glomerular and tubular cell cytoplasmic vacuolation, tubular desquamation, intra-luminal casts (hyaline and epithelial) formation and interstitial inflammatory cell infiltration.
Regarding PAS staining, in Cd(Cl)2 treated groups there was thickening of the basement membranes (BMs) of most glomerular blood capillaries, parietal layers of Bowman’s capsules, proximal convoluted tubular (PCT) and distal convoluted tubular (DCT) cells. This thickening became more obvious and intense with long exposure to Cd(Cl)2.
Silver impregnated sections revealed some fibrosis in the renal cortical parenchyma which became more evident and wide spread with increase duration of exposure.
Immuno-histochemical detection of COX2 showed that, COX2 expression was faint and restricted to macula densa cells in the control group while this expression after one and two weeks of Cd(Cl)2 exposure became higher than in control rats. This expression was not only restricted to macula densa cells but also extend to involve most PCT and DCT cells. This expression showed higher positivity and expressed in more numerous cells of PCTs and DCTs with increased duration of exposure (from one to two weeks), while apparent decreased of COX2 staining occurred after four weeks.
At the ultra-structural levels it was found that, Cd(Cl)2 administration produce minimal effect in one week exposed group while its effect became more obvious from two to four weeks of Cd(Cl)2 exposure. The renal glomeruli showed alteration in their fenestrae, pedicles and filtration slits. Furthermore more thickening in the glomerular BMs was noticed which became more noticeable along course of exposure. The majority of the PCT and DCT cells displayed different degrees of cellular alterations that were characterized by more numerous swollen mitochondria, lysosomes, vacuoles and partial loss of their basal infolding. Additionally more thickening in the cellular BMs was observed which became more evident with increase time of exposure.
In the current study there was a considerable amelioration in the degenerative changes affecting the kidney cortex when NSO was given with Cd(Cl)2. This was in the form of; less noticeable cytoplasmic vacuolation and minimal distortion of glomerular and tubular cells. Hemorrhages, inter-tubular fibrosis and thickening of the BMs (glomerular and tubular) appeared to be remarkably attenuated. NSO administration showed also reduction in the interstitial inflammatory cell infiltration and preservation of the general structural architecture. Fused pedicles, lysosomes and vesicular mitochondria appeared to be less numerous.
It could be concluded that nephron-toxicity induced by Cd(Cl)2 increased with the long duration of exposure and NSO administration ameliorate this toxic effect. Our study suggested that a diet rich in natural NSO or used as a herbal medicine could be useful to prevent Cd(Cl)2 induced nephron-toxicity in human who are highly exposed to that toxicant (eg. industrial areas or smokers). In the near future NSO could constitute a lead to discovery of unusual treatment for drug induced nephrotoxicity.
Further investigations on the mechanism of action of NSO are required and may have a considerable impact on future clinical treatment of patients with acute and chronic renal failure. Further studies are also needed to explain Cd - NSO interaction in condition of long term co-exposure and their consequences for health.