Effects of single dose administration of ifosfamide on testes and semen characteristics in the rabbit

Ypsilantis, Petros; Papaioannou, Nikolaos; Psalla, Dimitra; Politou, Maria; Simopoulos, Constantinos

doi:10.1016/s0890-6238(02)00127-2

Cited by 10 publications

(7 citation statements)

References 15 publications

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“…This was shown experimentally with weekly (Ypsilantis et al, 2003a) as well as with single‐dose (Ypsilantis et al, 2003b) administration of ifosfamide in animals. Testicular dysfunction was shown to be dose‐dependent (Ypsilantis et al, 2003a,b) and could be reversed after long follow‐up dependent on the treatment dose (Ypsilantis et al, 2003a). Longhi et al (2003) observed that ifosfamide affected testicular function in a dose‐dependent manner.…”

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

“…Ifosfamide is an alkylating agent with known gonadal toxic action (Ypsilantis et al, 2003a,b). This was shown experimentally with weekly (Ypsilantis et al, 2003a) as well as with single‐dose (Ypsilantis et al, 2003b) administration of ifosfamide in animals. Testicular dysfunction was shown to be dose‐dependent (Ypsilantis et al, 2003a,b) and could be reversed after long follow‐up dependent on the treatment dose (Ypsilantis et al, 2003a).…”

Section: Discussionmentioning

confidence: 99%

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Testicular Function in Poor‐Risk Nonseminomatous Germ Cell Tumors Treated With Methotrexate, Paclitaxel, Ifosfamide, and Cisplatin Combination Chemotherapy

Pectasides¹,

Pectasides²,

Papaxoinis³

et al. 2009

Journal of Andrology

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Our objective was to investigate the impact of methotrexate, paclitaxel, ifosfamide, and cisplatin (M-TIP) on longterm fertility in poor-risk nonseminomatous germ cell tumors (NSGCT). Thirty patients with poor-risk NSGCT (median age, 29 years; range, 17-62 years) were treated with methotrexate 250 mg/m 2 with folinic acid rescue (day 1) and paclitaxel 175 mg/ m 2 (day 1), followed by ifosfamide 1.2 g/m 2 and cisplatin 20 mg/m 2 (days 2-6). Treatment consisted of 4 cycles of M-TIP administered every 3 weeks. Twenty-one patients were continuously disease-free at a median follow-up of 5.3 years (range, 0.9-8.4 years). Sperm count and hormonal analyses were examined prechemotherapy (30 patients) and postchemotherapy (21 patients). Counts were classified as follows: lower than 1 6 10 6 /mL, azoospermia; 1-20 6 10 6 / mL, oligospermia (OS); higher than 20 6 10 6 /mL, normospermia (NS). Patients were followed for a median of 2.3 years (range, 0.9-3.8 years) postchemotherapy. The prechemotherapy median luteinizing hormone (LH) serum levels were slightly above the upper normal limit, whereas the serum levels of follicle-stimulating hormone (FSH) and testosterone (T) were within the reference interval. Eleven (52.3%) patients had NS prechemotherapy. Among the patients with NS, 72.7% still had NS following chemotherapy. Overall, 17 of 21 (80.9%; 33.3% OS and 47.6% NS) patients had recovery of spermatogenesis after treatment. The median FSH serum levels were significantly elevated at least 1 year postchemotherapy when compared with the pretreatment levels. Eighteen months after the completion of chemotherapy the median FSH levels had returned to the reference limits. Serum LH and T levels were unaffected by chemotherapy. Prior to chemotherapy 4 of 30 patients had fathered 5 children. Since completion of chemotherapy, 5 patients have fathered 5 children. The majority of men with poor-risk germ cell tumors who were treated with the M-TIP regimen demonstrated recovery spermatogenesis after treatment, and Leydig cell function was unaffected.Key words: Fertility, gonadal toxicity. J Androl 2009;30:280-286T he treatment of metastatic germ cell tumors (GCT) with the introduction of cisplatin-based chemotherapy results in the cure of approximately 80% of patients (Bosl and Motzer, 1997). In 1997, the International Germ Cell Cancer Collaborative Group (IGCCCG) (1997) published a new classification system based on data collected from more than 5000 GCT patients treated from 1975 to 1990. This system classifies patients with disseminated GCT into good-, intermediate-, or poor-risk groups on the basis of 3 criteria: the primary tumor site, the levels of serum tumor markers, and whether nonpulmonary visceral metastases are present. According to this classification system, patients allocated to the good-risk group have a 5-year survival rate of 92%, whereas patients in the intermediate-and poor-risk groups have 5-year survival rates of 82% and 48%, respectively. Patients with markedly elevated tumor markers, nonpulmonary viscer...

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Testicular Function in Poor‐Risk Nonseminomatous Germ Cell Tumors Treated With Methotrexate, Paclitaxel, Ifosfamide, and Cisplatin Combination Chemotherapy

Pectasides¹,

Pectasides²,

Papaxoinis³

et al. 2009

Journal of Andrology

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“…[22,23] as the amount causing a sub-lethal toxic (including nephrotoxic) effect in rats. On the same basis, the recommended single nephrotoxic dose of IF used for experimental purposes ranged between 60-240 in rabbits [24] to as much as 400 mg/kg b.w. in mice [25].…”

Section: Drug Dosesmentioning

confidence: 99%

Biochemical and Histological Evaluation of Kidney Function in Rats after a Single Administration of Cyclophosphamide and Ifosfamide

Dobrek¹,

Baranowska²,

Skowron³

et al. 2017

J Nephrol Kidney Dis

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Background: Cyclophosphamide (CP) and Ifosfamide (IF) are widely used cytotoxic agents. Both CP and IF exert some characteristic adverse drug reactions including kidney damage taking various clinical forms, depending on the applied dose or administration route. The aim of our study was to estimate kidney function using selected, classical biochemical parameters as well as analyzing the urinary concentration and excretion of a modern "kidney troponin" -neutrophil gelatinase-associated lipocalin-1 (NGAL-1) in rats after administration of a single CP or IF dose. Methods: 30 rats were divided into three groups (n=10 each; half males and females): group 1 -control (rats receiving i.p. saline solution); groups 2 and 3 -rats intraperitoneally treated with a single CP or IF dose of 150 mg/kg b.w., respectively. Following saline/CP/IF administration, animals were housed in single metabolic cages, to assess 24-hour diuresis and to obtain urinary samples for further laboratory assays. Finally, blood samples were collected and rats were sacrificed to perform autopsy with cystectomy and nephrectomy with subsequent histopathological analysis. Standard parameters of kidney function were assayed either in blood or in urine with an additional assessment of the urine NGAL-1 level.Results: Single administration of both CP and IF resulted in decreased pH of urine and proteinuria accompanied by an increased 24-hour urinary NGAL-1 excretion. Moreover, CP-treated rats demonstrated polyuria. Concentrations and 24-hour excretion of most classical, low-weight parameters were not different in both CP-and IF-treated rats compared to values observed in control animals.The histopathological analysis in CP/IF treated animals revealed presence of cystic inflammatory lesions and a normal kidney structure, with the exception of a mild to moderate congestive hyperemia. Conclusion:A single administration of CP and IF caused a functional kidney tubulopathy in study rats manifested by marked proteinuria with increased 24-hour NGAL-1 urinary excretion.

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“…İfosfamidin farklı dozlarının tek enjeksiyonlarını mütea-kip doza bağlı olarak tavşanların testis ve ek salgı bezi ağırlık-larında geçici azalma, benzer şekilde spermatositogenesis (240 mg/kg) ve spermiogenesis (60, 90 ve 120 mg/kg) ile epididimisteki sperm olgunlaşması olaylarında geçici baskılanmalara bağlı olarak oligo-, teratozoo-ve asthenozoo-spermi şekillen-mekte olup tedavi sonrası maksimum 8. haftada tekrar normale dönüşler meydana gelmektedir (116). Mutajenik etkili olan ifosfamid farelerde de doza bağımlı olarak testiküler germ hücrelerinde kromozomal aberasyonlara ve spermlerde morfolojik bozukluklara sebebiyet vermektedir (41,117).…”

Section: Sağlıklı Erkek Deney Hayvanlarındaki Etkileriunclassified

Kemoterapötiklerin erkek üreme sistemi üzerindeki yan etkileri ve koruyucu stratejiler

Türk¹

2013

mpj

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Effects of single dose administration of ifosfamide on testes and semen characteristics in the rabbit

Cited by 10 publications

References 15 publications

Testicular Function in Poor‐Risk Nonseminomatous Germ Cell Tumors Treated With Methotrexate, Paclitaxel, Ifosfamide, and Cisplatin Combination Chemotherapy

Testicular Function in Poor‐Risk Nonseminomatous Germ Cell Tumors Treated With Methotrexate, Paclitaxel, Ifosfamide, and Cisplatin Combination Chemotherapy

Biochemical and Histological Evaluation of Kidney Function in Rats after a Single Administration of Cyclophosphamide and Ifosfamide

Kemoterapötiklerin erkek üreme sistemi üzerindeki yan etkileri ve koruyucu stratejiler

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