Effect of zidovudine (AZT) on reproductive and hematopoietic systems in the male rat.
The effects of Zidovudine (AZT) on parameters of the reproductive and hematopoietic systems of male rats were evaluated and compared to those of the controls. Young male Wistar rats were divided into three groups. The control rats (Group 1) received no drug. AZT was administered via drinking water to rats in Groups 2 and 3 (0.1 mg/mL Group 2, and 1.0 mg/mL Group 3) for 4 weeks. Daily water intake and weekly body weight were monitored. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), prolactin (PRL) and intratesticular T levels were determined by specific radioimmunoassays. Serum AZT was measured by HPLC. Bone-marrow toxicity was monitored by colony-forming units of erythroid (CFU-E) and granulocyte-macrophage (CFU-GM) assays. The body weight of all rats increased 2-fold in four weeks, and no significant differences were observed between control and treated groups. Ventral prostate (VP) weight decreased significantly (P less than 0.05) by 32% in Group 2 and 27% in Group 3 rats, compared to the control group. Seminal vesicle (SV) weight decreased by 20% in Group 2 (NS) and 30% in Group 3 (P less than 0.05) rats. No significant differences were observed in testes weight or in the intratesticular sperm count between control and AZT-treated groups. Serum T levels (ng/mL) decreased significantly in Group 2 rats (2.8 +/- 0.4 in control to 1.7 +/- 0.2, P less than 0.05) but recovered (2.6 +/- 0.5) in Group 3 when compared to Group 1 (control). Serum LH and PRL levels showed a significant increase (P less than 0.05) in Group 3 compared to control or Group 2 rats. Serum FSH and intratesticular T levels showed no significant change. A significant (P less than 0.05) dose-dependent decrease in CFU-E and in CFU-GM was observed in AZT-treated rats compared to controls. These results demonstrate that the effects of AZT on the reproductive system in the male rat are more subtle and complex, compared to its significant effects on bone-marrow. This suggests that important interactions may exist between the endocrine and hematopoietic systems.
Sikka
S C
SC
Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112.
Gogu
S R
SR
Agrawal
K C
KC
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D003114:Colony-Forming Units Assay; D005640:Follicle Stimulating Hormone / Q000097:blood; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006413:Hematopoietic System / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011388:Prolactin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects*; D013739:Testosterone / Q000097:blood; D015215:Zidovudine / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*
D013739:Testosterone; D015215:Zidovudine; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone