الفهرس 
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Abstract
Mercury is one of the most common heavy metals, used for more than 3000 years in medicines, industries, gold mining and therapeutically. Mercury is the third most dangerous heavy metal and its toxicity causes serious risks to health through unfavorable biochemical and pathological effects. Mercury exists in three basic states: elemental Hg or Hg vapor, inorganic Hg, and organic Hg. Mercury chloride (HgCl2) is a highly toxic inorganic salt of Hg and is metabolized primarily in the liver and is being accumulated in the kidneys; consequently, the liver and kidneys are considered the main target organs for Hg damage. Conversely, zinc is one of the most important nutritional factors and has hepato-renal protective effects against toxicity of heavy metals through its antioxidant activity. The present study was designed to investigate the prophylactic effect and the therapeutic effect of zinc sulphate (ZnSo4) against mercuric chloride (HgCl2) toxicity.
Fifty-six male albino rats were divided into two experiments:
First experiment: To study the probable prophylactic effect of zinc sulphate against mercuric chloride toxicity at four weeks post-treatment. Twenty-four male albino rats were divided equally into three groups (8 rats per each) as follows: Control group, HgCl2-intoxicated group were Injected (s/c) with HgCl2 (1mg/kg .BW) thrice a week using insulin syringe, (HgCl2+ ZnSo4) prophylactic group were received ZnSo4 in drinking water at a dose level of 227 mg/liter and injected (s/c) with HgCl2 (1mg/kg .BW) thrice a week using insulin syringe. The experimental treatments were conducted for four weeks.
Second experiment: To study the probable prophylactic and therapeutic effect of zinc sulphate against mercuric chloride toxicity at eight weeks post-treatment. Thirty-two male albino rats were divided equally into four groups (8 rats per each) as follows: Control group, HgCl2-intoxicated group were Injected (s/c) with HgCl2 1mg/kg.BW thrice a week using insulin syringe., prophylactic group )HgCl2+ ZnSo4( were received ZnSo4 in drinking water at a dose level of 227 mg/liter and injected (s/c) with HgCl2 using insulin syringe and treated group (HgCl2 then ZnSo4) were Injected (s/c) HgCl2 )1mg/kg.BW( thrice a week using insulin syringe for four weeks then treated with ZnSo4 in drinking water at a dose level of 227 mg/liter for other four weeks. The experimental treatments were conducted for eight weeks.
At the end of the 4th week and at end of the 8th week blood samples were collected for evaluation of hemogram and for serum biochemical analysis. After each euthanization rats were eviscerated, then liver and kidney divided in to two parts: the first part kept frozen at -70 for assessment of reduced glutathione (GSH) and lipid peroxidation (LPO) contents while, the second one were kept in formalin 10% for histopathological examination.
Clinically, no mortalities were recorded in all experimental groups throughout the period of the experiment, except mercuric chloride (HgCl2) treated rats showed loss of appetite and depression.
Hematological findings:
All treated groups did not show any significant change in RBCs count, HCT values, Hb concentration, MCV, MCH and MCHC at four weeks post-treatment. However, at eight weeks post-treatment rats of (HgCl2) group showed a significant decrease in RBCs count, Hb concentration and HCT while, MCV showed a significant increase. On contrast, MCH showed a significant decrease in rats of (HgCl2+ ZnSo4) group and (HgCl2 then ZnSo4) group. On other hand, MCHC showed non-significant change in all treated groups when compared with control group.
The total leukocytic count, lymphocytes, monocytes, neutrophils and eosinophils did not show any significant change at four weeks post-treatment. While, at eight weeks post-treatment there were significantly decrease in total leukocytes and lymphocytes count in rats of (HgCl2) group, however, monocytes count showed a significant increase in rats of (HgCl2), (HgCl2+ ZnSo4) and (HgCl2 then ZnSo4) groups. Moreover, neutrophils and eosinophils count showed non-significant changes in all treated groups comparatively to control group. Concerning, blood platelets count exhibited a significant decrease in rats of (HgCl2) group only as compared to control group at eight weeks post-treatment.
Biochemical findings:
The serum activities of ALT and AST enzymes showed a significant increase in rats of (HgCl2) group and (HgCl2+ ZnSo4) group, the highest increase was observed in (HgCl2) group, followed by HgCl2+ ZnSo4) group, while the serum activity of GGT enzyme showed a significant increase in (HgCl2) group only at four weeks post-treatment as compared to control group. Moreover, at eight weeks post-treatment the serum ALT activity was significantly increased in rats of (HgCl2) group and (HgCl2 then ZnSo4) group, the highest increase was observed in (HgCl2) group, numerically followed by (HgCl2 then ZnSo4) group. Also, the serum AST activity was significantly increased in rats of (HgCl2), (HgCl2+ ZnSo4) and (HgCl2 then ZnSo4) groups, the highest increase was observed in (HgCl2) group, followed by (HgCl2 then ZnSo4) group then (HgCl2+ ZnSo4) group While, the serum GGT significantly increased in rats of (HgCl2) group only and did not show any significant changes in other treated groups comparatively with the control group.
The serum total protein, albumin and globulin did not show any significant changes in all treated groups as compared to control one at four weeks post-treatment. While, at eight weeks post-treatment the serum total protein and albumin showed a significant decrease only in rats of (HgCl2) group. However, the serum globulin showed non-significant change in all treated groups as compared to control one.
Blood urea and serum creatinine showed a significant increase in rats of (HgCl2) group and (HgCl2+ ZnSo4) group, the highest increase was observed in (HgCl2) group, followed by (HgCl2+ ZnSo4) group comparatively with the control one at four weeks post-treatment. Moreover, at eight weeks post-treatment blood urea showed a significant increase in rats of (HgCl2), (HgCl2+ ZnSo4) and (HgCl2 then ZnSo4) groups, the highest increase was observed in (HgCl2) group, followed by (HgCl2 then ZnSo4) then (HgCl2+ ZnSo4) group. However, serum creatinine showed a significant increase only in rats of GP.5as compared to control group.
Regarding to electrolytes, serum sodium, potassium, calcium and phosphorus levels showed non-significant changes in all treated groups as compared to the control one at four weeks post-treatment. While, at eight weeks post-treatment serum potassium and phosphorus levels showed a significant increase in rats of (HgCl2), (HgCl2+ ZnSo4) and (HgCl2 then ZnSo4) groups. However, the serum sodium level revealed a significant decrease in rats of (HgCl2), (HgCl2+ ZnSo4) and (HgCl2 then ZnSo4) groups. Also the serum calcium level showed a significant decrease only in rats of (HgCl2) group comparatively with the control group.
The serum total cholesterol and LDL-c levels showed a significant increase only in rats of (HgCl2) group. The serum triglyceride and VLDL-c showed a significant increase in rats of (HgCl2) and (HgCl2+ ZnSo4) groups. However serum HDL-c level showed a significant decrease only in rats of (HgCl2) group as compared to the control group at four weeks post-treatment. While, at eight weeks post-treatment serum total cholesterol level showed a significant increase in rats of (HgCl2) and (HgCl2+ ZnSo4) groups. However, the serum triglyceride, LDL-c and VLDL-c levels were significantly increase in rats of (HgCl2), (HgCl2+ ZnSo4) and (HgCl2 then ZnSo4) groups the highest increase was observed in (HgCl2) group, followed by (HgCl2 then ZnSo4) group then (HgCl2+ ZnSo4) group. While, serum HDL-c level showed a significant decrease in rats of (HgCl2), (HgCl2+ ZnSo4) and (HgCl2 then ZnSo4) groups the highest decrease was observed in (HgCl2) group, followed by (HgCl2 then ZnSo4) group then (HgCl2+ ZnSo4) group in comparison with control group.
Oxidant biomarkers:
The concentration of lipid peroxidation in liver and kidney homogenate expressed as malondialdehyde (MDA) showed a significant increase in rats of (HgCl2), (HgCl2+ ZnSo4) groups, the greatest increase was observed in (HgCl2) group, numerically followed by (HgCl2+ ZnSo4) group comparatively to control group at four weeks post-treatment. While, at eight weeks post-treatment the concentration of hepatic and renal GSH showed a significant decrease in rats of (HgCl2), (HgCl2+ ZnSo4) and (HgCl2 then ZnSo4) groups, the greatest decrease was observed in )HgCl2) group, numerically followed by (HgCl2 then ZnSo4) group then (HgCl2+ ZnSo4) group as compared to control group.
Histopathological findings:
During the 4th week of the experiment, the liver lesions of HgCl2-intoxicated rats were showed severe diffuse hydropic degeneration of hepatocytes beside multifocal hepatocytic necrosis with inflammatory cells and moderate inflammatory cell infiltration in the portal area. While, at 8th weeks post-treatment liver of (HgCl2+ ZnSo4) treated rats showed mild focal hydropic degeneration. Also, mild focal hepatic necrosis with mild inflammatory cell infiltration was evident. Moreover, at eight weeks post-treatment the liver of HgCl2-intoxicated rats showed multifocal hepatic necrosis with inflammatory cell infiltration. Also, advanced macrovesicular steatosis was noticed. There was marked fibroplasia in the portal area with presence of golden brown hemosiderin pigment either free or inside macrophages and hyperplasia of bile ductules. But, (HgCl2+ ZnSo4) treated rats revealed mild hydropic degeneration of hepatocytes. Also, congestion of portal vein and mild thickening of wall of bile duct were evident. Rats of (HgCl2 then ZnSo4) showed moderate hydropic degeneration of hepatocytes. Furthermore, multifocal hepatic necrosis with inflammatory cells infiltration was detected. There was moderate thickening of the portal area due to congestion of the portal vein, mononuclear infiltrates and marked fibroplasia.
Kidneys of HgCl2-intoxicated rats showed mild to moderate tubulointerstitial nephritis with mononuclear cell infiltration and Perivascular inflammatory cell infiltration. Moreover, there was tubular necrosis with desquamation of lining renal epithelium in tubular lumen. Some renal tubules contained hyaline cast in their lumena, others had attenuated renal epithelium with mononuclear cell aggregates .While, kidneys of (HgCl2+ ZnSo4) treated rats showed mild tubulointerstitial nephritis with mononuclear cell infiltration and presence of hyaline cast in lumena of some renal tubules at 4th weeks post-treatment. While, at eight weeks kidneys of mercuric chloride intoxicated rats showed severe tubulointerstitial nephritis represented by necrotic renal tubules with mononuclear cell infiltration. There were wide areas of hemorrhage and hyaline cast in the lumen of some renal tubules. However, rats of (HgCl2+ ZnSo4) group revealed mild tubulointerstitial nephritis with presence of hyaline cast in tubular lumen. But, rats of (HgCl2 then ZnSo4) showed moderate tubulointerstitial nephritis as well as presence of necrotic atrophied glomerular tuft.
Finally it could be concluded that:
HgCl2- intoxication induced harmful effects on hematological, biochemical parameters, as well as antioxidant status and histopathological architecture of both liver and kidney of male albino rats. These effects were time-dependent.
The use of ZnSo4 partially improved the HgCl2 induced hematobiochemical alterations and hepato- renal damage.
We advise to use ZnSo4 in diet as a prophylactic element to protect liver and kidney from the supposed toxicities or damages.