Testicular Function in Adult Rats Treated with the Alkylating Agent Chlorambucil

Delic, Julian I.; Stanley, Judith A.; Harwood, Janet R.

doi:10.3109/01485018608986960

Cited by 18 publications

(11 citation statements)

References 14 publications

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“…When the does of PCB was given as two equal fractions 1 week apart, the level of damage seen, within a given pretreatment group, was at about the same level. This is in contrast to some extent to our observations using the alkylating agent chlorambucil, which was more effective in producing sperrnatogonial stem-cell killing when given as multiple fractions [3].…”

Section: Discussioncontrasting

confidence: 55%

Protection of Spermatogenesis During Cancer Chemotherapy

Delic

1987

Archives of Andrology

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The ability of androgen pretreatment in adult Wistar rats to protect the spermatogonial stem cells from one or two doses of the cytotoxic procarbazine (PCB) was investigated. Survival of stem cells was assessed by a tubule regeneration assay. Ten weeks' pretreatment of the rats with 200 m2 silastic implants containing testosterone resulted in significant protection of the spermatogonial stem cells from PCB-induced damage. Androgen-pretreated rats given a single dose of 200 mglkg PCB demonstrated 86% tubule regeneration as opposed to 41% in rats pretreated with cholesterol. Similar values were obtained when the PCB dose was given as two weekly fractions of 100 mg/kg. The protective effect of androgen is present from the time of the initial challenge with the cytotoxic drug.

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Section: Discussioncontrasting

confidence: 55%

Protection of Spermatogenesis During Cancer Chemotherapy

Delic

1987

Archives of Andrology

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“…Interstitial edema is a testicular injury and a direct consequence of endothelial layer disruption, which liberates fluids from blood flow into interstitial tissue. Thus, testicular interstitial fluid volume can be increased by a variety of factors including testosterone level alterations [45] and toxic exposure [24,46,47]. Indeed, doxorubicin causes endothelial dysfunction and edema, as secondary effects of oxidative stress in the vascular wall.…”

Section: Discussionmentioning

confidence: 99%

Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status

Vendramini

Sasso-Cerri

Miraglia

2010

Reprod Biol Endocrinol

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BackgroundAmifostine is an efficient cytoprotector against toxicity caused by some chemotherapeutic drugs. Doxorubicin, a potent anticancer anthracycline, is known to produce spermatogenic damage even in low doses. Although some studies have suggested that amifostine does not confer protection to doxorubicin-induced testicular damage, schedules and age of treatment have different approach depending on the protocol. Thus, we proposed to investigate the potential cytoprotective action of amifostine against the damage provoked by doxorubicin to prepubertal rat testes (30-day-old) by assessing some macro and microscopic morphometric parameters 15, 30 and 60 days after the treatment; for fertility evaluation, quantitative analyses of sperm parameters and reproductive competence in the adult phase were also carried out.MethodsThirty-day-old male rats were distributed into four groups: Doxorubicin (5 mg/kg), Amifostine (400 mg/kg), Amifostine/Doxorubicin (amifostine 15 minutes before doxorubicin) and Sham Control (0.9% saline solution). "Standard One Way Anova" parametric and "Anova on Ranks" non-parametric tests were applied according to the behavior of the obtained data; significant differences were considered when p < 0.05.ResultsThe rats killed 30 and 60 days after doxorubicin treatment showed diminution of seminiferous epithelium height and reduction on the frequency of tubular sections containing at least one type of differentiated spermatogonia; reduction of sperm concentration and motility and an increase of sperm anomalous forms where observed in doxorubicin-treated animals. All these parameters were improved in the Amifostine/Doxorubicin group only when compared to Doxorubicin group. Such reduction, however, still remained below the values obtained from the Sham Control group. Nevertheless, the reproductive competence of doxorubicin-treated rats was not improved by amifostine pre-administration.ConclusionsThese results suggest that amifostine promotes a significant reduction of the doxorubicin long-term side effects on the seminiferous epithelium of prepubertal rats, which is reflected in the epidydimal fluid parameters in the adult phase. However, fertility status results suggest that such protection may not be effective against sperm DNA content damage. Further investigation of sperm DNA integrity must be carried out using amifostine and doxorubicin-treated experimental models.

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“…Absence of specific cell stages could be indicative of increased death of a specific cell type, death of cells as they reach a certain stage of differentiation, or a failure of previous cell stages to differentiate. Spermatogonial cell loss has been reported after exposure to antibiotics such as doxorubicin and bleomycin (Hou et al, 2005;Russell et al, 2000b;Shinoda et al, 1999), alkylating agents such as cisplatin and chlorambucil (Delic et al, 1986;Sawhney et al, 2005;Seaman et al, 2003;Zhang et al, 2001), nematocides such as dibromochloropropane (Meistrich et al, 2003), and DNA topoisomerase inhibitors such as etoposide (Russell et al, 2000a). Permanent infertility and irreversible Sertoli cell-only syndrome are generally believed to be a consequence of apoptotic loss of stem spermatogonia (Sawhney et al, 2005) and the duration of azoospermia is believed to be related to the number of stem cells killed (Meistrich et al, 1989).…”

Section: Macroscopic and Microscopic Evaluationmentioning

confidence: 99%