Display options
Share it on

Acta Histochem Cytochem. 2015 Aug 27;48(4):103-13. doi: 10.1267/ahc.14062. Epub 2015 Aug 20.

Vitamin D3 May Ameliorate the Ketoconazole Induced Adrenal Injury: Histological and Immunohistochemical Studies on Albino Rats.

Acta histochemica et cytochemica

Mahmoud Salah Khalil

Affiliations

  1. Department of Histology, Faculty of Medicine, Suez Canal University , Egypt ; Medical College, King Saud University , KSA.

PMID: 26379312 PMCID: PMC4564376 DOI: 10.1267/ahc.14062

Abstract

Ketoconazole (KZ) is used widely for treating the superficial, systemic fungal activities and hyperandrogenemic states. Its uses are limited by its deleterious effect on histological structure and function of the adrenal cortex. This study investigates whether vitamin D3 supplement can ameliorate the morphological changes induced by KZ. Thirty four adult male albino rats were randomized into control group (Group I) which was subdivided into: control 1 (n=7) and control 2 (n=7): In control 1, rats were intraperitoneal (I.P) injected once with 1 ml of polyethylene glycol-400 for 15 consecutive days and control 2 rats were injected I.P with (1 μg/kg) of vitamin D3 for the same period. Group II (n=10): rats were I.P injected with KZ (10 mg/100 g of body weight) once daily for 15 days; Group III (n=10): rats were I.P concomitantly injected with KZ and vitamin D3 similar doses to animals in groups II and control 2 respectively. Blood samples were collected to determine plasma ACTH, corticosterone and aldosterone levels. The right adrenal specimens sections were stained with Haematoxylin & Eosin and Masson Trichrome for histological studies and treated with Bax, Ubiquitin and vitamin D receptors for immunohistochemical studies. KZ induced adrenal cortical morphological changes in forms of disturbed adrenocorticocyte cytological architecture, nuclear changes, and intracellular lipid accumulation. KZ also increased adrenal Bax and Ub but decreased the vitamin D receptors immunopositive staining expression, in addition to increased plasma ACTH as well as decreased corticosterone and aldosterone levels. These changes were ameliorated by supplementing with vitamin D3.

Keywords: adrenal cortex; ketoconazole; rats; vitamin D3

References

  1. EMBO J. 1999 May 4;18(9):2330-41 - PubMed
  2. Am Fam Physician. 2003 Jun 15;67(12):2565-72 - PubMed
  3. Endocrinology. 2013 Nov;154(11):4018-29 - PubMed
  4. J Immunol. 2012 Mar 1;188(5):2127-35 - PubMed
  5. Eur Neuropsychopharmacol. 2000 Dec;10(6):429-35 - PubMed
  6. Clin Microbiol Rev. 1988 Apr;1(2):187-217 - PubMed
  7. Drug Metab Dispos. 2001 Nov;29(11):1366-76 - PubMed
  8. J Biochem Mol Toxicol. 2002;16(6):311-6 - PubMed
  9. J Steroid Biochem Mol Biol. 1991;40(1-3):381-9 - PubMed
  10. Autophagy. 2006 Jul-Sep;2(3):238-40 - PubMed
  11. J Lipid Res. 2011 Dec;52(12):2111-35 - PubMed
  12. J Biol Chem. 1997 Oct 17;272(42):26253-61 - PubMed
  13. Neuropsychopharmacology. 2003 Feb;28(2):379-83 - PubMed
  14. Antimicrob Agents Chemother. 1980 Jun;17(6):922-8 - PubMed
  15. Arch Biochem Biophys. 2001 Sep 1;393(1):106-16 - PubMed
  16. BMC Cancer. 2013 Apr 15;13:192 - PubMed
  17. Arch Intern Med. 1982 Nov;142(12):2137-40 - PubMed
  18. Drug Saf. 1999 May;20(5):451-8 - PubMed
  19. J Biol Chem. 2005 Mar 18;280(11):10491-500 - PubMed
  20. FEBS J. 2005 Aug;272(16):4080-90 - PubMed
  21. Biochem Biophys Res Commun. 2003 Jun 13;305(4):989-96 - PubMed
  22. Antimicrob Agents Chemother. 1995 Aug;39(8):1671-5 - PubMed
  23. Arch Biochem Biophys. 1989 Aug 1;272(2):459-65 - PubMed
  24. J Steroid Biochem Mol Biol. 2000 Dec 31;75(4-5):229-36 - PubMed
  25. Biochim Biophys Acta. 2007 Jun;1771(6):663-76 - PubMed
  26. Genomics. 2001 Jan 15;71(2):222-34 - PubMed
  27. J Cell Biochem. 2004 Jun 1;92(3):436-44 - PubMed
  28. Int J Endocrinol. 2013;2013:313528 - PubMed
  29. Mol Endocrinol. 1997 Dec;11(13):1961-70 - PubMed
  30. J Clin Invest. 1983 May;71(5):1495-9 - PubMed
  31. Drug Metab Rev. 2003 May-Aug;35(2-3):107-43 - PubMed
  32. Biochemistry. 1964 Feb;3:203-9 - PubMed
  33. Hepatol Res. 2000 May;17(2):112-125 - PubMed
  34. Chem Biol. 2005 Aug;12(8):931-9 - PubMed
  35. Klin Wochenschr. 1985 Jul 1;63(13):607-12 - PubMed
  36. Oncogene. 2004 Mar 15;23(11):2009-15 - PubMed
  37. Arch Pharm Res. 2005 Mar;28(3):249-68 - PubMed
  38. J Pharmacol Exp Ther. 2003 Jun;305(3):872-9 - PubMed
  39. Recent Results Cancer Res. 2003;164:3-28 - PubMed
  40. J Natl Cancer Inst. 1989 Apr 5;81(7):497-502 - PubMed
  41. Ann Intern Med. 1982 Sep;97(3):370-2 - PubMed
  42. Recent Pat Anticancer Drug Discov. 2007 Jan;2(1):31-58 - PubMed
  43. Cancer Res. 1990 Aug 1;50(15):4709-17 - PubMed
  44. Anat Rec. 1984 Dec;210(4):603-15 - PubMed
  45. Indian J Endocrinol Metab. 2013 Mar;17(2):245-8 - PubMed
  46. FEBS Lett. 1993 Jul 12;326(1-3):285-8 - PubMed
  47. J Urol. 2002 Oct;168(4 Pt 1):1583-8 - PubMed
  48. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8251-5 - PubMed
  49. Steroids. 2001 Mar-May;66(3-5):381-9 - PubMed
  50. Klin Wochenschr. 1989 Jul 17;67(14):707-12 - PubMed
  51. Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14754-9 - PubMed
  52. Mol Endocrinol. 1999 Oct;13(10 ):1686-94 - PubMed
  53. Biochim Biophys Acta. 1975 Oct 9;404(2):309-20 - PubMed
  54. Hepatology. 2001 Nov;34(5):926-34 - PubMed
  55. J Clin Invest. 1983 Jul;72(1):404-8 - PubMed
  56. Drug Metab Dispos. 2000 Feb;28(2):118-24 - PubMed
  57. Cell Tissue Res. 1991 Jul;265(1):1-9 - PubMed
  58. Comp Biochem Physiol C Toxicol Pharmacol. 2010 Jan;151(1):113-21 - PubMed
  59. Environ Health Perspect. 2003 Mar;111(3):255-61 - PubMed
  60. Br J Cancer. 1988 Oct;58(4):493-6 - PubMed
  61. Physiol Rev. 1998 Oct;78(4):1193-231 - PubMed

Publication Types