An animal model of testicular toxicity by cyclosporine: evaluation and protection.
CyclosporineA (CsA) improves the survival of patients who benefited from transplantation. However, its use is generally limited by its side effects. The aim of our study was to measure, in an experimental model, the changes of the testosterone plasma levels after 21 days of CsA treatment and to explain the mechanism of this modification. After treatment, the levels of CsA, testosterone, corticosterone, transaminases were measured. The cytotoxic effect of CsA was evaluated by microscopic observation. The experimental study showed that CsA had no effect on the plasmatic levels of hepatic enzymes - alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl-transferase - because their plasma concentrations in treated rats did not differ from those of the sham group. The plasma concentration of corticosterone was not modified, the plasma level of testosterone decreased when the dose of cyclosporine was increased to 4 mg/kg/day. The photonic microscope observation showed that the number of Leydig cells was increased and the electronic microscope observation showed mitochondria alteration. The treatment by CsA and trimetazidine did not correct the alteration caused by CsA. N-benzyl-N'-(2-hydrox-3, 4-dimethyloxybenzyl)-pipeazine did not protect the mitochondrial function but partially protected mitochondria structure from the deleterious effect induced by CsA. The decrease of the plasma level of testosterone induced by CsA was due to the inhibition of the mitochondrial 20-22 desmolase which blocked the formation of the testosterone precursor and the destruction of the mitochondria structure.
Ali
Ridha Ben
RB
Animal Experimentation Unit, Medecine University of Tunis, Tunis, Tunisia. ridha_benali@voila.fr
Klouz
Anis
A
Boubaker
Samir
S
Lakhal
Mohamed
M
Belkahia
Chalbi
C
D000818:Animals; D003345:Corticosterone / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000633:toxicity*; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013739:Testosterone / Q000097:blood*
D007166:Immunosuppressive Agents; D013739:Testosterone; D016572:Cyclosporine; D003345:Corticosterone