الفهرس 
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Abstract
Cyclosporine A (CsA) is one of the powerful immunosuppressive drug which has improved the quality of life and survival rate of transplant patients and also used in the treatment of autoimmune diseases. However, its use is limited by many as side effects mainly nephrotoxicity and reprotoxicity.
N-acetylcysteine (NAC) is a thiol and a potent antioxidant which has been found to play a role to decrease cyclosporine induced toxicity.
The present study is an experimental study. It was performed to:
• Study cyclosporine renal and testicular toxicity.
• Study the possible protective effect of N-acetylcysteine on cyclosporine toxicity on kidney and testis.
The present study was conducted on 50 sexually mature male albino rats. Their weight ranged from (180:220) gm at the beginning of the experiment.The protocol of ethics and husbandry conditions of animal research were considered according to the guide of care and use of laboratory animals approved by the ethical committee of Faculty of Medicine,Sohag University.
Rats were divided into 5 groups 10 rats each
group A: Negative control group, where animals received no treatment.
group B: Positive control group where animals received olive oil at a dose of 0.5 ml / day orally by gavage for 4 weeks.
group C: Cyclosporine treated group, where animals were treated by cyclosporine dissolved in olive oil at a dose of 25 mg/kg per day orally by gavage for 4 weeks. (Zal et al., 2007)
group D: NAC-treated group, where animals were treated by NAC dissolved in water at a dose of 600 mg/kg per day orally by gavage for 4 weeks. (Saleh, 2014)
group E: Combined CsA and NAC treated group, where animals were treated by CsA dissolved in olive oil at a dose 25 mg/kg /day and NAC dissolved in water at a dose 600 mg/kg /day. Both were given orally by gavage for 4 weeks.
Results:
Kidney:
The biochemical results of the present study of urea and creatinine revealed that cyclosporine treated group showed significant increase in the serum urea and creatinine levels. While combination of NAC with cyclosporine cause significant decrease in the serum urea and creatinine levels as compared to cyclosporine only group but levels still higher than levels of control group.
Histo-pathological examination of kidney from cyclosporine only group revealed dilatation of urinary space with congestion and lobulation of glomerullar capillaries in the renal corpusle. Proximal convoluted tubules showed degeneration of their cells with irregularity and destruction of brush border. Degeneration of distal convoluted tubules with exfoliation of some cells inside the lumen and the peritubular capillaries were congested and extravasated.
While examination of the cyclosporine+NAC treated group revealed less damage in the renal corpuscles in the form of decrease of urinary space and decrease congestion of glomerular capillaries as compared to cyclosporine only group. Some of P.C.T & D.C.T were more or less similar to the control group, other tubules were degenerated
Testis:
The biochemical results of the present study of testosterone level revealed that cyclosporine treated group showed significant decrease in the serum testosterone level as compared to control group. While combination of NAC with cyclosporine cause significant increase in the serum testosterone level as compared to cyclosporine only group but levels still lower than levels of control group.
Histo-pathological examination of testis from cyclosporine only group revealed degenerative changes in the tubules with dislocation of germ cells into the lumen and irregular outlines. Congested blood capillaries in the interstitial tissue.
While examination of the cyclosporine+NAC treated group revealed that histological alterations were less marked as most of tubules appear more or less as control group a part of some tubules show degeneration as compared to cyclosporine treated group. The interstitial tissue, leydig cells and blood capillaries are similar to control group.
Conclusion
It has been found that cyclosporine has toxic effects on kidney and testis both functionally and pathologically. These effects attributed to oxidative stress.
Kidney exposure to cyclosporine for 4 weeks had shown kidney damage with increase in serum urea and creatinine levels.
Testis exposure to cyclosporine for 4 weeks had shown testicular damage with decrease in serum testosterone level.
N-acetylcystein is an antioxidant and its combination with cyclosporine attenuate renal and testicular toxicity induced by cyclosporine but not provide full protection.
Recommendations
•It is advisable to restrict prolonged use of cyclosporine and decrease its dose to avoid its renal and testicular toxic effect.
•It is recommended to use antioxidant as N-acetylcysteine in combination with cyclosporine to decrease its toxicity.
•Further studies should be performed to find other antioxidants that can provide full protection from cyclosporine toxicity.
• Further studies should be performed to find other powerful immunosuppressive drug with fewer side effects than cyclosporine.