Doxorubicin-induced Testicular Toxicity Research Articles

Effects of Purslane Shoot and Seed Ethanolic Extracts on Doxorubicin-Induced Testicular Toxicity in Albino Rats

Effects of Purslane Shoot and Seed Ethanolic Extracts on Doxorubicin-Induced Testicular Toxicity in Albino Rats

Effects of Purslane Shoot and Seed Ethanolic Extracts on Doxorubicin-Induced Testicular Toxicity in Albino Rats

3 Abstract: The clinical usefulness of anthracycline antineoplastic antibiotic, doxorubicin (DOX) is restricted since it has several acute and chronic side effects. The effect of doxorubicin (4 mg/kg b.w/week) without or with oral administration of purslane (Portulaca oleracea) shoot ethanolic extract (50mg/kg b.w./day) and purslane seed ethanolic extract (50mg/kg b.w./day) co-treatments for 6 weeks was evaluated in adult male rats. Serum testosterone luteinizing hormone (LH), follicle stimulating hormone (FSH) level were assayed. Testis lipid peroxidation (indexed by MDA) and antioxidants like glutathione (GSH), glutathione-S-transferase (GST), peroxidase (POX), superoxide dismutase (SOD), catalase (CAT) levels in testis were assessed. The data revealed a significant decrease in serum levels concentration of testosterone, LH and FSH levels in doxorubicin-injected rats. In addition, testis glutathione, glutathione transferase, peroxidase, SOD and CAT levels were decreased while lipid peroxidation concentration in the testis was increased as a result of doxorubicin injection. Co-administration of ethanolic purslane and seed extracts potentially improved the adverse changes in serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) levels with an increase in testis antioxidants levels and reduction in lipid peroxidation. In conclusion, it can be suggested that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX testicular toxicity without harmful side effects. (Walaa G. Hozayen; Osama M. Ahmed and Haidy Tamer Abo Sree Effects of Ethanolic Purslane Shoot and Seed Extracts on Doxorubicin-Induced Testicular Toxicity in Albino Rats. Life Sci J 2013; 10(3): 2550-2558). (ISSN: 1097-8135). http://www.lifesciencesite.com. 369

Effect of dexrazoxane on doxorubicin-induced testicular toxicity.

2556 Background: Seminal advances in anti-cancer therapy result in growing numbers of young male cancer survivors for whom treatment-induced infertility represents a major late-term concern. Doxorubicin (DXR) has been previously shown to exert toxic effect on the testicular germinal epithelium. Based upon the cardioprotective traits of dexrazoxane (DEX), we aimed to study its potential effect to reduce DXR-induced testicular toxicity. Methods: Male mice were injected intraperitoneally with 5mg/kg DXR or 100mg/kg DEX or the combination of both and scarified at one month post treatment. Saline-injected mice served as controls. Testes were excised, weighed and further processed. For oxidative stress determination glutathione assay was performed on testes' lysates and P38 protein levels were determined by western blot analysis. Bax levels were used to assess apoptosis. Immunohistochemistry and confocal microscopy were used to study the effect of DXR, DEX and their combination, on the testis histology as well as on the spermatogonial reserve. Results: One month after DEX and DXR treatment, a striking decline in testicular weight was observed (decrease by 60% compared with control values; decrease of 54% in DXR-only treated mice; p<0.05). DEX prevented DXR-induced oxidative stress. However, DEX enhanced DXR-induced apoptosis within the testes and furthermore, the combination depleted the spermatogonial reserve one month after treatment. Conclusions: DEX activity in the testis may differ from its activity in cardiomyocytes. Adding DEX to DXR may exacerbate DXR-induced testicular toxicity.

Ginseng intestinal metabolite-I (GIM-I) reduces doxorubicin toxicity in the mouse testis

The protective effect of ginseng intestinal metabolite-I (GIM-I) against doxorubicin-induced testicular toxicity was investigated in 5-week-old ICR male mice. GIM-I was administered orally to mice at a dose of 50 mg/kg daily for 4 weeks. From the second week, doxorubicin was coadministered intraperitoneally to the animals at a dose of 3 mg/kg once a week for 3 weeks (a total of 9 mg/kg). The body weight, spermatogenic activities (Sertoli cell, repopulation, and epididymal indices), and serum levels of lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) were significantly decreased by doxorubicin treatment ( P<0.01), while the combined treatment of GIM-I with doxorubicin resulted in parameters similar to the control. In the testes of doxorubicin-treated animals, almost all of the germ cells disappeared and were replaced by fibrinoid debris in the seminiferous tubules. Germ cell injury was significantly attenuated by GIM-I coadministration. The mRNA for phospholipid hydroperoxide glutathione peroxidase (PHGPx), a testis-specific antioxidant, was greatly decreased by doxorubicin treatment, and less decreased with GIM-I coadministration. These findings indicate that GIM-I may be partially protective against doxorubicin-induced testicular toxicity.

Regional doxorubicin delivery reduces testicular toxicity

Many anti-cancer drugs cause infertility. Regional delivery of these agents is a potential method to avoid this problem. We investigated the protective effect of normothermic testicular circulatory arrest on gonadal toxicity during doxorubicin administration in the Sprague-Dawley rat. Four groups of eight rats each were used. Animals in group 1 received no treatment. Rats in group 2 were anesthetized and received a bolus of intravenous doxorubicin (6 mg/kg). In groups 3 and 4, normothermic circulatory isolation of the left testis was induced by cross-clamping of the spermatic cord and gubernaculum immediately before doxorubicin administration. This was maintained for 15 min after doxorubicin administration in group 3 and for 45 min in group 4. Cessation and return of testicular blood flow were confirmed by Doppler. On Day 56, all rats were killed and necropsied. Testicular toxicity was evaluated qualitatively by histology and quantitatively by measurement of testicular weight, sperm count, repopulation index, and epididymal index. The results indicated that 15 min of testicular circulatory isolation mitigated testicular toxicity to a small extent and that 45 min of circulatory isolation provided moderate protection against doxorubicin-induced testicular toxicity.

Testicular Cytotoxicity of Intravenous Doxorubicin in Rats

Although the testicular cytotoxicity of many chemotherapeutic drugs has been evaluated in mice, their small size can pose technical problems. In this report, we describe doxorubicin-induced testicular toxicity in a larger animal model, the Sprague-Dawley rat. Fifty-three rats were used for this study. On day 0, rats in the treatment groups were anesthetized and given different single intravenous doses of doxorubicin (0.1 to 30mg./kg.). On day 56 ± 2, all surviving rats were killed and necropsied. Testicular toxicity was evaluated qualitatively by histology and quantitatively by testicular weight, sperm head count, repopulatipn index and epididymal index. The histologic effects of doxorubicin on the heart, liver and kidney were qualitatively evaluated. Progressive dose-dependent testicular atrophy and oligospermia occurred at low and intermediate dosages of doxorubicin (0.1 to 5mg./kg.). Marked testicular atrophy, oligospermia and germinal aplasia were observed at high dosage of doxorubicin (10mg./kg.). LD50 for animal mortality at day 56 ± 2 for doxorubicin appears to be 10mg./kg. These findings are similar to those reported in mice. The rat is a suitable model for the study of techniques to avoid drug-induced testicular damage.