Vitamin B17 Ameliorates Methotrexate-Induced Reproductive Toxicity, Oxidative Stress, and Testicular Injury in Male Rats

Felemban, Shatha Ghazi; Aldubayan, Maha; Alhowail, Ahmad; Almami, Ibtesam S

doi:10.1155/2020/4372719

Cited by 28 publications

(24 citation statements)

References 30 publications

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“…Rats are very often used as the animal experimental model for the assessment of the impact of drugs on the male reproductive system [ 40 – 42 ], bones [ 43 , 44 ], and as well as for the evaluation of direct tissue toxicity [ 45 , 46 ]. Laboratory methods and reagents are available for measurements of hormone levels and immunological studies in rats, ensuring repeatability and facilitating the comparison of results.…”

Section: Introductionmentioning

confidence: 99%

“…The schedule is also personalized due to comorbidities and the risk of drug-drug interactions so the potential for a single agent to cause selective tissue toxicity (not only for drug combinations) may be very important in terms of making clinical decisions [38,39]. Rats are very often used as the animal experimental model for the assessment of the impact of drugs on the male reproductive system [40][41][42], bones [43,44], and as well as for the evaluation of direct tissue toxicity [45,46]. Laboratory methods and reagents are available for measurements of hormone levels and immunological studies in rats, ensuring repeatability and facilitating the comparison of results.…”

Section: Introductionmentioning

confidence: 99%

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Long‐Term Administration of Abacavir and Etravirine Impairs Semen Quality and Alters Redox System and Bone Metabolism in Growing Male Wistar Rats

Matuszewska

Nowak

Niżański

et al. 2021

Oxidative Medicine and Cellular Longevity

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Highly active antiretroviral therapy (HAART) is used in HIV-infected patients. Alongside the prolongation of patients’ life, adverse side effects associated with long-term therapy are becoming an increasing problem. Therefore, optimizing of HAART is extremely important. The study is aimed at evaluating the toxicity of abacavir and etravirine in monotherapy on the reproductive system, liver, kidneys, and bones in young, sexually mature, male rats. Thirty-six 8-week-old male Wistar rats randomized into three 12-animal groups received either normal saline (control), abacavir 60 mg/kg (AB group), or etravirine 40 mg/kg (ET group) once daily for 16 weeks. Semen morphology, oxide–redox state parameters (MDA, SOD, catalase, GPx, glutathione, GSH/GSSG ratio) in tissue homogenates (testes, liver, kidneys), and serum samples were studied. In bones, microcomputed tomography and a four-point bending test were performed. Total sperm count, sperm concentration, motility, and sperm morphology did not differ significantly in AB or ET groups compared to the control. In the flow cytometry of semen, an increased percentage of cells with denatured DNA was noticed for both tested drugs. However, no significant changes of oxide–redox state in testicular homogenates were found, except of increased SOD activity in the AB-receiving group. Additionally, ET significantly altered catalase and GPx in the liver and SOD activity in kidneys. Abacavir decreased catalase in the liver and GSH levels in kidneys. AB caused significant changes to bone microarchitecture (bone volume fraction, trabecular number, connectivity density, total porosity) and increased Young’s modulus. Etravirine had a greater impact on macrometric parameters of bones (tibial index, mid-tibial diameter, femur length). After 4 weeks in the ET group, a lower 1,25-dihydroxyvitamin D3 serum concentration was found. The results showed that abacavir and etravirine disturb oxidative stress. An increase in the percentage of sperms with chromatin damage suggests decreased fertility in rats receiving the studied drugs. Both drugs affected bone formation in growing rats. Additionally, etravirine disturbed vitamin D metabolism.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long‐Term Administration of Abacavir and Etravirine Impairs Semen Quality and Alters Redox System and Bone Metabolism in Growing Male Wistar Rats

Matuszewska

Nowak

Niżański

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…In addition, the male genital system is also adversely affected by MTX. An increase in degenerated seminiferous tubules with apoptotic cells and a decrease in proliferative cells in the germinal epithelium have been reported [1,[3][4][5][6][7][8]. Various mechanisms have been proposed to explain its side effects, but not yet fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…Various mechanisms have been proposed to explain its side effects, but not yet fully elucidated. MTX induces apoptosis by causing DNA damage [1, 3-5, 7, 8], disrupting the oxidant and anti-oxidant balance [3][4][5][6][7][8][9] and increasing inflammation [5,6,10] thereby leading to toxicity in male reproductive systems. Anti-oxidants and anti-inflammatory compounds such as folic and folinic acid [1], propolis [3], zinc [4], chrysin [5],…”

Section: Introductionmentioning

confidence: 99%

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Bitter melon (Momordica charantia) fruit extract ameliorates methotrexate‐induced reproductive toxicity in male rats

Kanpalta¹,

Özbeyli²,

Şen³

et al. 2021

Marmara Medical Journal

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Objective: Methotrexate (MTX) is a drug commonly used for the treatment of malign neoplastic and inflammatory diseases. Antioxidant and anti-inflammatory effects of bitter melon (BM) were reported. The aim of this study was to examine the effects of BM fruit extract on MTX-induced testicular and epididymal damage. Materials and Methods: Sprague Dawley male rats were divided into three groups (n=8) as control, MTX and MTX+BM. A single dose of MTX (20 mg/kg) was injected intraperitoneally to the MTX and MTX+BM groups. BM fruit extract (600 mg/kg) was applied to the MTX+BM group orally for 5 days. Testes were examined for general histopathology, proliferating and apoptotic cells. The epididymis samples were used for the evaluation of sperm morphology. Oxidative and inflammatory markers were analysed biochemically. Results: Increased abnormal spermatozoa, degenerated seminiferous tubules with increased apoptotic cells and decreased proliferative cells were observed in the MTX group. TNF-α, IL-1β, 8-hydroxy-2-deoxyguanosine and caspase-3 levels increased, superoxide dismutase and catalase levels decreased in both testis and epididymis samples. All these histological and biochemical parameters were ameliorated in the MTX+BM group. Conclusion: Methotrexate causes testis damage by decreasing spermatogenic cells and increasing apoptosis through oxidative stress and inflammation. BM extract improves testis and epididymis damage with its possible anti-oxidant and anti-inflammatory effects.

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Selenium mitigates methotrexate‐induced testicular injury: Insights from male NMRI mice model

Gholami,

Nemati,

Zarasvand

et al. 2024

Birth Defects Research

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Background and AimChemotherapy, particularly with methotrexate (MTX), often elicits testicular toxicity, leading to impaired spermatogenesis and hormone imbalances. This study aimed to investigate the potential protective effects of selenium (Se) against MTX‐induced testicular injury.Materials and MethodsMale mice were divided into control, MTX, Se, and MTX + Se groups. Histopathological examination involved the preparation of testicular tissue sections using the Johnsen's tubular biopsy score (JTBS) for spermatogenesis evaluation. Biochemical tests included the assessment of testosterone, malondialdehyde (MDA), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) levels. Real‐time quantitative polymerase chain reaction (RT‐qPCR) was employed to analyze the expression of caspase 3 (casp3), tumor protein 53 (p53), B‐cell lymphoma 2 (Bcl2), and Bcl2‐associated X protein (Bax) genes. Statistical analysis was performed using ANOVA and Tukey's tests (p < .05).ResultsHistopathological analysis revealed significant testicular damage in the MTX group, with decreased spermatogenesis and Leydig cell count, while Se administration mitigated these effects, preserving the structural integrity of the reproductive epithelium. Biochemical analysis demonstrated that MTX led to elevated malondialdehyde (MDA) levels and reduced testosterone, LH, and FSH levels, suggesting oxidative stress and Leydig cell dysfunction. Gene expression analysis indicated that MTX upregulated proapoptotic genes (casp3, p53, and bax) while downregulating the antiapoptotic Bcl2 gene. In contrast, Se treatment reversed these trends, highlighting its potential antiapoptotic properties.ConclusionOur findings underscore the potential of Se as a therapeutic agent to mitigate the reproductive toxicity associated with MTX‐induced testicular injury. Se exerts protective effects by regulating oxidative stress, preserving hormone balance, and modulating apoptotic pathways. These results suggest that Se supplementation could be a promising strategy to alleviate chemotherapy‐induced testicular damage and preserve male fertility.

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Vitamin B17 Ameliorates Methotrexate-Induced Reproductive Toxicity, Oxidative Stress, and Testicular Injury in Male Rats

Cited by 28 publications

References 30 publications

Long‐Term Administration of Abacavir and Etravirine Impairs Semen Quality and Alters Redox System and Bone Metabolism in Growing Male Wistar Rats

Long‐Term Administration of Abacavir and Etravirine Impairs Semen Quality and Alters Redox System and Bone Metabolism in Growing Male Wistar Rats

Bitter melon (Momordica charantia) fruit extract ameliorates methotrexate‐induced reproductive toxicity in male rats

Selenium mitigates methotrexate‐induced testicular injury: Insights from male NMRI mice model

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