Related Experiment Videos
Testicular cytotoxicity of intravenous methotrexate in rats
F E Johnson1, S A Farr, M Mawad
1Department of Surgery, St. Louis University Medical Center, MO 63110-0250.
Abstract:
Although the testicular cytotoxicity of methotrexate has been evaluated in the rat, previous models have utilized routes other than the intravenous one, and have generally employed multiple-dose regimens. In this report, we describe testicular toxicity in the Sprague-Dawley rat following a single intravenous bolus of methotrexate (0-700 mg/kg body weight [BW]), with necropsy 56 days later. Testicular toxicity was evaluated qualitatively by histology and quantitatively by testicular weight, sperm head count, modified Johnsen score, repopulation index, and epididymal index. Effects of methotrexate on heart, lung, liver, and kidney histology were evaluated qualitatively. Oligospermia occurred at low and intermediate dosages of methotrexate, but testicular atrophy was not observed. LD50 at day five for methotrexate appears to be approximately 300 mg/kg BW using this regimen. This model will facilitate the study of techniques to avoid drug-induced testicular damage.
Insights
Methotrexate causes reduced sperm counts in rats after a single intravenous dose, but not testicular atrophy. This study establishes a model for investigating methods to prevent drug-induced testicular damage.
Area of Science:
- Toxicology
- Reproductive Biology
- Pharmacology
Background:
- Previous studies on methotrexate's testicular toxicity in rats used non-intravenous routes and multiple doses.
- A standardized model for evaluating single-dose intravenous methotrexate testicular toxicity is needed.
Purpose of the Study:
- To characterize testicular toxicity in Sprague-Dawley rats following a single intravenous bolus of methotrexate.
- To establish a reliable model for studying testicular damage induced by methotrexate.
Main Methods:
- Rats received a single intravenous dose of methotrexate (0-700 mg/kg BW).
- Testicular toxicity was assessed via histology, testicular weight, sperm head count, Johnsen score, repopulation index, and epididymal index.
- Histology of heart, lung, liver, and kidney was also evaluated.
Main Results:
- Oligospermia was observed at low and intermediate methotrexate doses.
- No testicular atrophy was noted.
- The 5-day lethal dose 50 (LD50) was approximately 300 mg/kg BW.
Conclusions:
- Single intravenous administration of methotrexate induces oligospermia in rats without causing testicular atrophy.
- This model provides a foundation for developing strategies to mitigate methotrexate-induced testicular toxicity.