Effect of Cyclosporin A associated with nó-de-cachorro (Heteropterys aphrodisiaca, O. Mach, 1949) infusion on Wistar rats ventral prostate

Author(s)

Karine Moura Freitas

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2011-02-18

Examining board members

Mary Anne Heidi Dolder; Rejane Maira Góes; Daniele Lisboa Ribeiro

• Advisor: Mary Anne Heidi Dolder; Sebastião Roberto Taboga

Abstract

Cyclosporin A (CsA) is an immunosuppressive drug widely used in the post-operative treatment after organ transplants and against auto-immune diseases. However, various side effects have been associated with the use of this drug, including nephrotoxicity, hepatotoxicity, tremors, hypertension, hyperlipidemy, hypercalcicity, hypertrichosia and hyperplasticity of the gums. Besides these, damage to the male reproductive system, such as diminished testosterone production and testicular dysfunction, have been extensively documented. Heteropterys aphrodisiaca is a bush, typical of the Brazilian "Cerrado" region. It is known as "nó-de-cachorro" and used in traditional medicine as a tonic and an aphrodisiac drink. Previous studies confirm the efficiency of H. aphrodisiaca against the side effects of CsA in rat testicles. As a consequence, this research was undertaken with the aim of determining the possible collateral effects of CsA in the ventral prostate of Wistar rats and to verify whether the infusion of H. aphrodisiaca would be efficient to diminish the possible collateral effects of CsA in this organ. Thirty adult Wistar rats (90 days old) were divided into five groups (n=6 in each). Group I (control) was treated with water, Group II with CsA, group III received the H. aphrodisiaca infusion, group IV was treated simultaneously with CsA and H. aphrodisiaca infusion and group V received CsA or H. aphrodisiaca infusion on alternate days. CsA was administered in the dose of 15 mg/kg/day and the infusion in a volume of 0.5 ml per animal (infusion prepared with 25 g of dry ground roots in 100 ml of boiling water). All treatments were given daily for 56 days. After this period the rats were weighed and euthanized. Testis, epididymis, vesicular gland, coagulating gland and the ventral prostate were collected and weighed. The ventral prostate was divided into three portions. One was fixed in Karnovsky fixative and processed for inclusion in methacrylate. This portion was used for morphological, morphometrical and stereological analysis of the tissue. A second portion, fixed in the same manner, was processed for inclusion in Epon and analyzed with the transmission electron microscope. The last portion was fixed in Metacarn and included in paraffin to be used for immunohistochemistry of the androgen receptor and the TUNEL technique for apoptosis. The morphological, morphometrical, stereological and ultrastructural analyses showed that the H. aphrodisiaca infusion did not cause any alteration of the prostatic tissue. On the other hand, CsA treatment resulted in severe damage to the tissue, reducing the lumen, epithelium, muscular and non-muscular stroma. Atrophied epithelium was observed after CsA administration. Ultrastructural analysis showed that the atrophied epithelium had reduced organelles involved in protein secretion (rough endoplasmic reticulum and Golgi complex) which probably causes decreased secretory activity of the cells. The simultaneous treatment of CsA and H. aphrodisiaca apparently reduced the prostatic damage, since these were less damaged when compared to the prostate of animals that received only CsA. No alteration was found in the pattern of immunohistochemical labeling for androgen receptors and the apoptotic index, for all experimental groups. The results showed that CsA treatment caused structural damage to the prostate which probably reflected functional damage to the organ. The protective action of the H. aphrodisiaca infusion against the collateral effects of CsA was also confirmed for this organ. (AU)

• FAPESP's process: 09/07824-3 - Effect of cyclosporine A associated with "nó-de-cachorro" infusion (Heteropterys aphrodisiaca, O. Mach, 1949) on the prostate of Wistar rats
• Grantee: Karine Moura de Freitas
• Support Opportunities: Scholarships in Brazil - Master