Abstract

Methotrexate (MTX; 4-amino-10-methylfolic acid) is a folic acid reductase inhibitor used to treat autoimmune diseases and certain types of cancer. Testicular toxicity resulting from MTX is a significant side effect that may cause subsequent infertility. The present study was conducted to examine the ameliorating effects of vitamin B17 (VitB17) against testicular toxicity induced by MTX in male rats. A total of 50 male albino rats were equally divided into five groups [control group; vitamin B17 group (VitB17) administered VitB17 only; methotrexate group administered MTX only; cotreated group, (VitB17+MTX) and posttreated group (MTX+VitB17)]. In methotrexate group (MTX), a significant decrease was observed in body weight and the testicular weight, as well as the levels of plasma testosterone, luteinizing hormone and follicle-stimulating hormone compared with control. The sperm count, viability, morphology index, total motility, and progressive motility also decreased in MTX rats compared with control. Furthermore, the levels of reduced glutathione, catalase, and superoxide dismutase, as well as proliferating cell nuclear antigen protein expression, in the testicular tissue decreased in MTX compared with control. In addition, MTX caused a significant increase in DNA and tissue damage compared with control. However, VitB17 ameliorated these effects, indicating that it has a preventative and curative effect against MTX-induced reproductive toxicity in male rats. The protective effect of VitB17 may be associated to its antioxidant properties as it possibly acts as a free-radical scavenger and lipid peroxidation inhibitor, as well as its protective effect on the levels of GSH, SOD, and CAT.

Highlights

  • The testes are known to incur injury resulting from exposure to both chemotherapeutic and toxic environmental agents [1,2,3,4]

  • Various side effects were observed in animals injected with MTX, such as loss of body weight, lack of activity, weakness, and yellowish body hair

  • A 15 ± 3:2% mortality rate was recorded in the MTX group, while a 12 ± 1:5% mortality rate was recorded for the animal cotreated group (VitB17+MTX)

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Summary

Introduction

The testes are known to incur injury resulting from exposure to both chemotherapeutic and toxic environmental agents [1,2,3,4]. There are concerns regarding the toxicity of MTX [8,9,10], it has been used to treat certain types of cancer, such as breast, skin, neck, and lung cancers, as well as lymphoma, osteosarcoma, and acute leukemia [11]. This use has induced significant side effects, such as low blood cell counts, hair loss, mouth sores, and diarrhea, as well as liver, lung, nerve, and kidney damage [12, 13]. Testicular damage is an important potential side effect of MTX that can lead to infertility in males [14]

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