The protective effects of alpha lipoic acid on methotrexate induced testis injury in rats

Pınar, Neslihan; Çakırca, Gökhan; Özgür, Tümay; Kaplan, Mahir

doi:10.1016/j.biopha.2017.11.078

Cited by 57 publications

(53 citation statements)

References 23 publications

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“…The pharmacologic activity of ALA has been widely studied due to its important antioxidant function in animals and humans. In rats, ALA has been found to attenuate testicular injury induced by exposure to various toxins by inhibiting oxidative stress in the testes [24,25]. In the current study, HS was found to cause histological changes in testicular tissue, as evidenced by hematoxylin and eosin staining.…”

Section: Discussionsupporting

confidence: 51%

“…Oxidative and ER stress also play important roles in bovine granulosa cells after HS [13]. Additionally, it has been shown that ALA inhibits oxidative lesions caused by methotrexate in rat testes [25] and it has a protective role in response to various cell and tissue injury processes, by inhibiting ER stress in vitro and in vivo [39,40]. Similar to these reports, the current study showed that HS induced higher protein expression levels of GRP78 and CHOP, two well-known ER stress markers, implying that ER stress was activated in chicken testes after exposure to HS.…”

Section: Discussionmentioning

confidence: 99%

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Oxidative Stress and Endoplasmic Reticulum Stress Are Involved in the Protective Effect of Alpha Lipoic Acid Against Heat Damage in Chicken Testes

Xiong

Yin

et al. 2020

Animals

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Heat stress (HS) causes testicular injury, resulting in decreased fertility. Alpha-lipoic acid (ALA) is a well-known antioxidant. The aim of this study was to investigate the protective effects of ALA on HS-induced testicular damage in chickens. Histological changes; biomarkers of oxidative stress, including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA); markers of endoplasmic reticulum (ER) stress, including glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP); apoptosis-related modulators, including Bax, Bcl-2, and caspase 3, in testicular tissue and serum testosterone levels were evaluated in chickens under heat stress. Heat stress induces spermatogenic cell abnormalities in chicken testes. Compared to the HS group, the histomorphological abnormalities in testicular tissue were visibly ameliorated, with significant increases in the enzyme activities of GPx, SOD, and CAT, increased serum testosterone concentration, and decreased MDA levels in the ALA + HS group. Consistent with these results, compared with the HS group, the protein levels of GRP78, CHOP, caspase 3, and Bax were significantly decreased, whereas Bcl-2, StAR, and 3β-HSD protein levels were increased in the ALA + HS group. Collectively, these findings suggest that ALA significantly ameliorates the heat-induced histomorphological abnormalities in the testes and decreased testosterone production by potentiating the activities of anti-oxidative enzymes (GPx, SOD, and CAT), inhibiting ER stress-related apoptotic pathways (Bax, Bcl-2, and caspase 3), and increasing steroidogenic gene (StAR and 3β-HSD) expression in chickens.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Endoplasmic Reticulum Stress Are Involved in the Protective Effect of Alpha Lipoic Acid Against Heat Damage in Chicken Testes

Xiong

Yin

et al. 2020

Animals

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“…[ 22 ] In another study investigating MTX‐induced testicular damage in rats, the researchers similarly found that the serum testosterone level decreased after MTX administration. [ 6 ]…”

Section: Discussionmentioning

confidence: 99%

“…[22] In another study investigating MTX-induced testicular damage in rats, the researchers similarly found that the serum testosterone level decreased after MTX administration. [6] MTX causes seminiferous tubule degeneration, decreased testosterone level, sperm count, and motility. It may also cause infertility due to its side effects on the testicular tissue.…”

Section: Discussionmentioning

confidence: 99%

“…[ 3,4 ] Recently, MTX has been used to treat many diseases including rheumatoid arthritis, psoriasis, systemic lupus erythematosus, dermatomyositis, lymphoma, leukemia, osteosarcoma, and lung and breast cancer. [ 5,6 ] Unfortunately, the drug demonstrates undesirable toxic effects. Previous studies have shown that MTX has toxic effects on bone marrow, liver, lung, kidney, intestine, central nervous system, and gonads.…”

Section: Introductionmentioning

confidence: 99%

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Ameliorating effects of agomelatine on testicular and epididymal damage induced by methotrexate in rats

Aslankoç

Özmen

Elli̇dağ

2020

J Biochem & Molecular Tox

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The aim of this study was to investigate the possible prophylactic effects of agomelatine (AGO) against testicular and epididymal damage induced by methotrexate (MTX) in rats. Twenty‐four male Wistar albino rats were divided into three groups: Group I (control group), Group II (MTX group: 20 mg/kg MTX, i.p, single dose), and Group III (MTX+AGO group: 20 mg/kg MTX, i.p, single dose+40 mg/kg AGO; gavage, 7 days). The rats were killed under anesthesia 24 hours after the last AGO application. Testicular and epididymal tissues were bilaterally removed for morphometric, biochemical, pathological, and immunohistochemical analyses. Body, testicular, and epididymal weights were measured. Malondialdehyde (MDA), superoxide dismutase, catalase, and glutathione peroxidase levels were measured in testes. Sperm count, hyperemia, edema, inflammatory reaction, degenerated and necrotic cells were evaluated by histopathological analysis. In addition, inducible nitric oxide synthase (iNOS), granulocyte colony‐stimulating factor (G‐CSF), osteopontin (OPN), and heat shock protein‐70 (HSP70) immune reactions were analyzed in testes and epididymides. Decreased epididymal weights, increased MDA levels, decreased sperm count, hyperemia, edema, inflammatory reaction, and degenerated and necrotic cells were observed in the MTX group. In addition, iNOS, HSP70, G‐CSF, and OPN immune reactions were increased. AGO improved morphometric, biochemical, histopathological, and immunohistochemical findings. The present study confirms that MTX induces testicular and epididymal damage both biochemically and immunohistochemically. However, AGO demonstrated ameliorative effects on both biochemical and pathological findings of the current study.

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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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The protective effects of alpha lipoic acid on methotrexate induced testis injury in rats

Cited by 57 publications

References 23 publications

Oxidative Stress and Endoplasmic Reticulum Stress Are Involved in the Protective Effect of Alpha Lipoic Acid Against Heat Damage in Chicken Testes

Oxidative Stress and Endoplasmic Reticulum Stress Are Involved in the Protective Effect of Alpha Lipoic Acid Against Heat Damage in Chicken Testes

Ameliorating effects of agomelatine on testicular and epididymal damage induced by methotrexate in rats

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

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