CYCLOSPORIN INDUCED EFFECTS ON FOETAL KIDNEY IN ALBINO MICE

Authors

  • N Tawakal
  • M Tahir
  • S Waqas

Abstract

Background: Cyclosporin A (CsA) is an immunosuppressive agent which is used to prevent graft
rejection and to treat autoimmune disorders. Its teratogenic effects remain unexplored despite its
extensive use even during pregnancy. Current study was, therefore, undertaken to investigate the
effects of CsA on the developing kidney. Methods: Twelve pregnant mice were divided into two
groups, A and B, having six animals each. Cyclosporin was freshly prepared in normal saline daily
and administered subcutaneously by a single dose of 50 mg/kg in the morning to experimental
group B during pregnancy from day 0 to day 18. The control group A was given comparable
volume of normal saline only. The pregnant mice were sacrificed at the end of experimental
period. The foetal kidneys were dissected and fixed in 10% formalin for histological preparations.
Results: The results showed that weight of the foetuses and their kidneys exposed to CsA was
consistently reduced. The mean weight of the foetuses exposed to CsA was 1.34±0.08 g as
compared to 1.48±0.18 g in the control group whereas the mean kidney weight from CsA treated
group was 9.47±0.27 mg when compared to the control having 10.79±0.53 mg. Morphometric
analysis revealed reduction in total number of glomeruli and hypertrophy of remaining glomeruli.
The total number of glomeruli/mm2 in the kidneys from CsA treated group was 26.85±4.43 as
compared to 41.33±3.66 from the control group and the mean diameter of glomeruli from the
foetuses of groups A and B was 7.11±0.47 mm and 8.66±0.63 mm respectively; the differences
between the groups A and B of the animals on all the parameters above were statistically
significant (p<0.000). Conclusion: The results of the investigation indicated that CsA
administration to the pregnant dams produced deleterious effects of on the developing kidney in
mice. On the analogy of the results, comparable effects of CsA are expected in case of human;
this, however, needs further investigations.
Keywords: Cyclosporin A, nephrotoxicity

References

Bar Oz B, Hackman R, Einarson T, Koren G. Pregnancy

outcome after cyclosporin therapy during pregnancy: A metaanalysis. Transplantation. 2001;71:1051-5.

Sgro MD,Barozzino T, Mirghani HM, Semer M, Moscato L,

Akoury H.Pregnancy outcome post renal transplantation.

Teratology 2002;65:5-9.

Flechner SM, Katz AR, Rogers AJ, Van Buren C, Kahan BD.

The presence of cyclosporin in body tissues and fluids during

pregnancy. Am J Kidney Dis 1985;5(1): 60-63.

Venkataramaran R, Koneru B, Wang CCP, Burckart GJ,

Starzl TE. Cyclosporin and its metabolites in mother and

baby. Transplantation 1988;46:468-9.

Mason R, Thomson A, Whiting P. Cyclosporin-induced

fetotoxicity in the rat. Transplantation. 1985; 39: 9-12.

Earm JH, Kim J, Tischer CC, Madsen KM. Cyclosporin A

treatment during pregnancy impairs rat distal nephron

development. J Am Soc Nephrol 1999;10:403.

Gilbert T, Gaonach S, Moreau E, Merlet-Benichou C. Effect

of Cyclosporin A on rat metanephros differentiation in vitro.

J Am Soc Nephrol. 1994;5:623.

Tendron A, Decramer S, Justrabo E, Gouyon JB, Semama

DS, Gilbert T. Cyclosporin administration during pregnancy

induces a permanent nephron deficit in young rabbits. J Am

Soc Nephrol 2003;14:3188-96.

US food and drug administration. Toxicological principles

for safety assessment of food ingredients and guidelines for

developmental toxicity studies. Red book 2000. Food and

Drug Administration, Center for safety and applied nutrition,

Washington, DC. Available at: http://www.fda.gov/Food/

GuidanceComplianceRegulatoryInformation/GuidanceDocu

ments/FoodIngredientsandPackaging/Redbook/default.htm

Doublier S, Amri K, Searin D, Moreau E, Merlet-Benichou

C, Striker GE, et al. Overexpression of human insulin like

growth factor binding protein-1 in the mouse leads to

nephron deficit. Pediatr Res.2001;49:660-6.

Sterio DC. The unbiased estimation of number and sizes of

arbitrary particles using the dissector. J Micro 1984;134:127-36.

Schreuder MF, Nyengaard JR, Fodor M, Van Wijk JAE,

Delemarre van de Waal HA. Glomerular number and

function are influenced by spontaneous and induced low birth

weight in rats. J Am Soc Nephrol 2005;16:2913-9.

Hood JC, Robinson WF, Clark WF. The structural

appearance of renal and other basement membrane in the

J Ayub Med Coll Abbottabad 2010;22(1)

http://www.ayubmed.edu.pk/JAMC/PAST/22-1/Tawakal.pdf

Bull terrier model of autosomal dominant Alport syndrome.

Am J Kidney Dis 2000;113:455-7.

Maeda M, Yabuki A, Suzuki S, Matsumoto M, Taniguchi K,

Nishinakagawa H. Renal lesion in spontaneous insulin

dependent diabetes mellitus in the non obese diabetic mouse

acute phase of diabetes. 2003;40:187-95.

Okada A, Yabuki A, Matsumoto M, Suzuki S. Development

of gender differences in DBA/ Cr mouse kidney morphology

during maturation. J Vet Med Sci 2005;67:877-82.

Merlet-Benichou C, Gilbert T, Vilar J, Moreau E, Freund N,

Lelievre-Pegorier M. Nephon number: Variability is the

rule: causes and consequences. Lab Invest 1999;79:515-27.

Merlet-Benichou C, Gilbert T, Muffat-Joly M, LelievrePegorier M, Leroy B. Intrauterine growth retardation (IUGR)

leads to a permanent nephron deficit in the rat. Pediatr

Nephrol 1994;8(2):175-80.

Manalich R, Reyes L, Herrera M, Melendi C, Fundora I.

Relationship between weight at birth and number and size of

renal glomeruli in humans. A histomorphmetric study.

Kidney Int 2000;58: 770-3.

Brenner BM, Garcia DL, Anderson S. Glomeruli and blood

pressure. Less of one more the other? Am J

Hypertens.1988;1(4 Pt 1):335-47.

Gilbert T, Lelievre Pegorier. Long term effects of mild

oligonephronia induced in utero by gentamycin in the rat.

Pediatr Res 1991; 30:450-6.

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Published

2010-03-01

How to Cite

Tawakal, N., Tahir, M., & Waqas, S. (2010). CYCLOSPORIN INDUCED EFFECTS ON FOETAL KIDNEY IN ALBINO MICE. Journal of Ayub Medical College Abbottabad, 22(1), 69–72. Retrieved from https://demo.ayubmed.edu.pk/jamc/index.php/jamc/article/view/3088

Issue

Vol. 22 No. 1 (2010): JOURNAL OF AYUB MEDICAL COLLEGE, ABBOTTABAD

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ORIGINAL ARTICLE

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