الفهرس 
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Abstract
Renal fibrosis is a final common pathway leading to progressive
loss of function in chronic kidney disease (CKD). The degree of renal
fibrosis predicts the prognosis of chronic kidney disease. CKD is a major
cause of mortality and a serious global health challenge. Worldwide,
nearly 1.5 million people need renal replacement therapy, and the
incidence of CKD has increased significantly over the last decades. In
Egypt, both the incidence and the prevalence rates of CKD are increasing
in various areas over time. Renal fibrosis is a pathological hallmark of
CKD, which is manifested by extensive fibroblast activation.
CKD results from a variety of causes such as diabetes,
hypertension, nephritis, inflammatory and infiltrative diseases, renal and
systemic infections, kidney disease, autoimmune diseases, renal hypoxia,
trauma, nephrolithiasis and obstruction of the lower urinary ways,
chemical toxicity and others. Mercury considered the most common toxic
metal causes nephrotoxic effects, which mainly accumulated in the renal
proximal tubular cells. Consequently, cause tubular necrosis. Therefore,
new strategies for diagnosis and treatment of CKD are much needed to
reduce its morbidity and mortality.
N N’-diphenyl-1, 4-phenylenediamine, a gray or dark gray powder,
used as a polymerization inhibitor and antioxidant. Mercury chlorideinduced
renal fibrosis was prevented by an antioxidant DPPD, which
inhibit interstitial fibrosis by scavenge free radicals giving electron(s) to
them, protecting cells from oxidative stress. So, the present study aimed
to evaluate the effect of N N’-diphenyl-1, 4-phenylenediamine on
development of renal fibrosis that induced by mercuric chloride in rats.This study was carried on 81 female Sprague–Dawley rats (body
weight 170 – 220 gm). Rats were bred and maintained in an airconditioned
animal house with specific pathogen free conditions, and
were subjected to a 12:12-h daylight/darkness and allowed unlimited
access to chow and water. All the ethical protocols for animal treatment
were followed and supervised by the animal facilities, Medical
Experimental Research Centre, Faculty of Medicine, Mansoura
University. 21 rats were died and the remaining 60 rats were divided into
3 groups as follow:
(1) Control group, where 20 Rats will receive corn oil and served as the
control.
(2) Mercuric chloride group, where 20 Rats will receive mercuric
chloride (4 mg / kg, i.p.) at the start of experiments.
(3) Mercuric chloride + DPPD group, where 20 Rats will receive
mercuric chloride (4 mg / kg, i.p.) at the start of experiments and three
days after mercuric chloride administration, rats will be given DPPD (0.5
g / kg, i.p.) every two days.
Samples of the kidneys, urine and blood collected from each rat
after 8 days of HgCl2 (or saline) treatment, for biochemical and
histopathological examination.
The following results were obtained:-
1. Urinary NAG significant increase in (HgCl2 and HgCl2 + DPPD
groups) compared to control group with; p < 0.001. Also, Total
protein significant increase in HgCl2 group compared to (control and
HgCl2 + DPPD groups) with; p < 0.001.2. Creatinine and urea significant elevate in HgCl2 group compared with
control group (p < 0.001). DPPD significant reduce serum creatinine
and urea levels (p < 0.001).
3. Extreme highly significant decrease found in serum creatinine
clearance level in HgCl2 group compared to (control and HgCl2 +
DPPD groups) with; p < 0.001.
4. The level of serum Magnesium significant increase in HgCl2 group
compared to (control and HgCl2 + DPPD groups) with; p < 0.001.
5. Collagen forming and fibrosis estimated by hydroxyproline content
examination in the kidney tissues. At day 8, hydroxyproline
significant increase in HgCl2 group compared to control group. DPPD
significant attenuated hydroxyproline formation in rats treated with
HgCl2 + DPPD (p ≤ 0.001).
6. High significant elevation (p < 0.001) of NO level observed in HgCl2
group compared to (control and HgCl2 + DPPD groups).
7. In HgCl2 injected rats, SOD and CAT activity significant reduced
compared to control group with; p < 0.001. Treatment with DPPD
significant attenuated the inhibitory effect of HgCl2 on SOD and CAT
activity with; p < 0.001.
8. Histopathological examination for the kidney tissue sections using
H&E stain showed that rats treated with HgCl2 + DPPD had a
significant decrease in tubular injury and significant increase in the
percent of normal tubules (p <0.001) compared with the group
injected with HgCl2 only.
9. We use Masson’s trichrome stain to investigate renal fibrosis and
collagen deposition (blue stained area). Rats treated with HgCl2 +
DPPD showed a significant decrease in collagen deposition and renal
fibrosis percent area compared to the group treated with HgCl2 only
(p <0.001).10. Next, we examined α-SMA expression in the kidney caused by
HgCl2 us ing immunohistochemistry. The percent area of α-SMApositive
cells significant increase in the group injected with HgCl2
only compared with (control and HgCl2 + DPPD groups) with; p <
0.001. Also, DPPD treated group showed no significant change in α-
SMA-positive cells percent area compared to the control group.
11. The ROC curve results analysis suggested that the diagnostic
accuracy of kidney tissue (Hydroxyproline, CAT and NO) were the
same and superior; in the order of (Hydroxyproline, CAT and NO) >
SOD > Creatinine Clearance (AUC = 1, 0.995, 0.903, respectively).
Differentiating rats with renal fibrosis (n = 20) from rats treated with
DPPD (n = 20).
Conclusion: We concluded that an antioxidant DPPD able to retard the
progression of renal interstitial fibrosis and collagen formation induced
by HgCl2. Further studies needed to find the role of ROS in pathogenic
and progressive mechanisms leading to the fibrosis induced by HgCl2
also the antioxidant DPPD anti-fibrotic effect.