Abstract

Methotrexate (MTX) is a cytotoxic drug used to treat a wide range of cancers and non-cancerous conditions. However, it can cause unfavorable acute toxic effects in several organs, including the testis. Equisetum arvense L. (E. arvense) extract is effective in counteracting oxidative stress-related disorders. This study assessed the preventive effect of E. arvense extract against MTX-induced testicular toxicity. Gas chromatography-mass spectroscopy (GC-MS) was used to analyze the active constituents of E. arvense extract. Testicular toxicity was induced via MTX injection (0.5 mg/kg/ twice a week for 4 weeks). Forty male albino rats were divided into 4 groups: I- control (Cont); II: MTX; III: E. arvense (500 mg/kg/daily for 10 weeks); and IV: E. arvense + MTX. E. arvense main active constituents were squalane (15%), ascorbic acid per methyl (9.55%), phytol (8.69%), 2-pyrroline 1,2-dimethyl (8.63%), and octacosane (8.23%). Treatment of MTX injected rats with E. arvense produced a significant rise in body weight, serum testosterone and luteinizing hormone. E. arvense significantly increased the sperm counts, viability, and motility relative to the MTX injected rats. The levels of testicular oxidative stress and inflammation significantly reduced in the MTX rats treated with E. arvense. Furthermore, E. arvense markedly improved the testicular tissue and seminiferous tubules’ pathologic features in MTX-treated rats. E. arvense significantly decreased lipid peroxidation products, interleukin-1 beta, tumor necrosis factor-alpha while increasing superoxide dismutase levels. E. arvense prevented MTX-induced testicular damage via anti-inflammatory and antioxidant activities.

Highlights

  • In recent years, the epidemiology of cancers in Saudi Arabia has increased threefold [1]

  • MTX is a folic acid reductase inhibitor cytotoxic agent used to treat a large number of malignant tumors and nonneoplastic diseases [3,4]

  • The Gas chromatography-mass spectroscopy (GC-MS) chromatogram analysis of E. arvense demonstrated the presence of 28 components corresponding to the peaks Fig. (1) and Table (1)

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Summary

Introduction

The epidemiology of cancers in Saudi Arabia has increased threefold [1]. Cancer treatment includes the use of numerous chemotherapeutic agents [2]. MTX is a folic acid reductase inhibitor cytotoxic agent used to treat a large number of malignant tumors (acute lymphoblastic leukemia, osteosarcoma, lung, breast, skin, neck, and head cancers) and nonneoplastic diseases (rheumatoid arthritis) [3,4]. Several studies have shown that MTX induced damage of testicular seminiferous tubule, apoptosis of spermatocyte, reduction of sperm number, and infertility in males [7,8,9,10,11]. Numerous studies have linked MTX-induced testicular damage to an imbalance between antioxidant factors and free radical levels [7,12,13,14]

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