Effect of Cyclosporin A, with or without Heteropterys tomentosa (A. Juss.) administration, on Wistar rats' liver, kidney, testis, epididymis, prostate and thymus

Author(s)

Karine Moura Freitas

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2014-10-24

Examining board members

Mary Anne Heidi Dolder; Juliana Castro Monteiro; Tatiana Carla Tomiosso; Grasiela Dias de Campos Severi Aguiar; Patricia Aline Boer

• Advisor: Mary Anne Heidi Dolder

Abstract

Cyclosporin A (CsA) is an immunosuppressive drug used after organ transplantation and against auto immune diseases. Despite CsA widely use as immunosuppressant, this drug causes diverse side effects as: nephrotoxicity, hepatotoxicity and male reproductive organs (testis and ventral prostate) impairment. Those CsA-related side effects are probably related to the CsA pro oxidant properties that causes imbalance among reactive oxygen species generation and antioxidant enzymes production. Heteropterys tomentosa, native plant from Brazilian cerrado, a savanna-like biome, is popularly used as tonic and stimulant of brain functions and as an aphrodisiac plant. H. tomentosa¿s efficiency against CsA side effects to the testis and ventral prostate has been scientifically proved. Moreover, H. tomentosa either reduced the alterations caused by CsA to plasma biochemical parameters that are hepatotoxicity markers. The aim of the present study was evaluate the effects of CsA to the liver, kidney, testis, epididymis, ventral prostate and thymus. If there are alterations CsA-induced, evaluate if H. tomentosa infusion alter these effects. Lastly we aimed to evaluate if H. tomentosa infusion interfere on CsA immunosuppressive capacity. CsA treatment for 21 days caused minor alterations to the liver tissue; this result was not observed after the administration of the infusion for 56 days. The simultaneous treatment with CsA and H. tomentosa caused hepatic alterations different from those observed in the animals treated with only CsA. The nephrotoxicity CsA-induce was time related; the kidney of animals treated with CsA had small substances accumulation (casts) on juxtamedullary tubules lumina, alteration to the proximal tubules were not evident. After 56 days of treatment there was huge casts on juxtamedullary tubules and some proximal tubules had vacuolization. These kidney¿s alterations were present in the groups treated with CsA and CsA+H. tomentosa. H. tomentosa administration did not caused alteration to the kidney tissue. The treatment with CsA, H. tomentosa and both simultaneously did not caused effects to the testis, however, CsA administration for 56 days caused alterations to the epididymis and ventral prostate; these alteration were not observe after the treatment with CsA+H. tomentosa. CsA caused reduction on the number of lymphocytes in the peripheral blood after the administration for 21 or 56 days, simultaneously with H. tomentosa or not. Furthermore, the thymus tissue had structural alterations caused by CsA, administrated alone or simultaneously to H. tomentosa (for 21 or 56 days). These results confirm CsA immunosuppression even after the administration with H. tomentosa simultaneously. The present study shows that CsA-induced effects to the kidney, epididymis and ventral prostate are time dependents. Moreover, the treatment with H. tomentosa reduced the alteration caused by CsA to the epididymis and ventral prostate. Finally, this study proved that H. tomentosa did not alter the immunosuppressant properties of Cyclosporin A (AU)

• FAPESP's process: 11/01160-6 - Does the "nó-de-cachorro" (Heteropterys aphrodisiaca, O. Mach, 1949) infusion relieves the CsA collateral effects or amendts its imunossupressive activity in Wistar rats?
• Grantee: Karine Moura de Freitas
• Support Opportunities: Scholarships in Brazil - Doctorate