Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: Intervention of folic and folinic acid

Padmanabhan, Seetharamaiyer; Tripathi, Durga Nand; Vikram, Ajit; Ramarao, P.; Jena, Gopabandhu

doi:10.1016/j.mrgentox.2008.11.011

Cited by 98 publications

(91 citation statements)

References 70 publications

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“…While vitamin E and L-carnitine decreased the MDA values increased by MTX, they also increased the SOD values decreased by MTX. MTX decreased sperm count and caused an increase in the rate of spermhead abnormalities (35,36). Moreover, it has also been reported that MTX, administered in different doses, can cause diameter thinning in seminiferous tubular, decreases in spermatogenic cell content, vacuolization, and edema in the interstitial region (35,37).…”

Section: Discussionmentioning

confidence: 95%

The effect of vitamin E and L-carnitine against methotrexate-induced injury in rat testis

Yüncü¹,

Bükücü²,

Bayat³

et al. 2015

Turk J Med Sci

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Background/aim: Methotrexate (MTX), used commonly as an antimetabolite drug in cancer therapy, leads to acute toxic side effects in tissues or organs containing rapidly dividing cells, such as bone marrow, gastrointestinal mucosa, and seminiferous tubules. In this study, we investigated the protective effects of vitamin E and L-carnitine against MTX-induced injury in rat testis.Materials and methods: Rats were divided into 4 groups, including the control group. The study took 17 days and the animals received daily doses of 0.5 mL/kg saline, 250 mg/kg vitamin E, or 500 mg/kg L-carnitine intraperitoneally. The experimental groups received 20 mg/kg methotrexate intraperitoneally on days 3 and 10.Results: Weight loss, testicular weight loss and marked histological injuries, increased malondialdehyde levels, and decreased superoxide dismutase levels were only observed in the MTX-treated groups. Vitamin E and L-carnitine treatments did not affect MTXinduced weight loss or testicular weight loss, but they inhibited MTX-induced testicular histological injuries. Vitamin E and L-carnitine treatments suppressed the increases in malondialdehyde levels and the decreases in superoxide dismutase levels. Conclusion:Vitamin E and L-carnitine treatments decreased MTX-induced testicular histological injuries, and these results were supported by biochemical measurements.

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Section: Discussionmentioning

confidence: 95%

The effect of vitamin E and L-carnitine against methotrexate-induced injury in rat testis

Yüncü¹,

Bükücü²,

Bayat³

et al. 2015

Turk J Med Sci

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“…[8] In studies performed in mice, and rats, MTX had decreased testicular weight, and sperm counts, increased number of sperm head abnormalities, and damaged DNAs of seminiferous tubuli, and spermatozoa. [19][20][21] In a study by Vardı et al [8] the authors demonstrated that MTX decreases effectiveness of antioxidant enzyme system, and renders cells vulnerable to harmful effects of ROS leading to destructive changes in testis. Oxidative stress had caused destructive changes in testicular tissue, and ameliorating effects of an antioxidant (chlorogenic acid) on testicular damage had been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

The histopathological evaluation of healing effects of vitamin C administered before methotrexate therapy on testicular injury induced by methotrexate

Sayılmaz

Karabulut

Özgörgülü

2016

Turkish Journal of Urology

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Objective: Methotrexate (MTX) leads to acute toxic side effects in tissues or organs containing rapidly dividing cells such as seminiferous tubules. In this study, we investigated the protective effects of vitamin C against MTX-induced injury in rat testis. Material and methods:A total of 31 rats were divided into 4 groups, including the control group. The study was completed within 4 weeks and the rats received daily doses of 2 mL/kg SF, 100 mg/kg vitamin C and 10 mg/kg/day MTX i.p according to their groups. The mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score were determined by histologic examination of each group. Results:The vitamin C + MTX group showed more similarity with the control group. Statistically significant results were achieved between groups as for mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score. When compared with the group which received vitamin C after MTX therapy, values for mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score were significantly higher in the group which received vitamin C before initiation of MTX therapy. Conclusion:Vitamin C decreased MTX-induced testicular histological injuries, especially when used before MTX therapy.

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“…MTX is a classical antimetabolite and it is currently widely used as a major chemotherapeutic agent for human malignancies such as acute lymphoblastic leukemia, malignant lymphoma, osteosarcoma, breast cancer and head and neck cancer (2,4,5).…”

Section: Introductionmentioning

confidence: 99%

Influence of Reduced Folate Carrier and Dihydrofolate Reductase Genes on Methotrexate-Induced Cytotoxicity

et al. 2010

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Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: Intervention of folic and folinic acid

Cited by 98 publications

References 70 publications

The effect of vitamin E and L-carnitine against methotrexate-induced injury in rat testis

The effect of vitamin E and L-carnitine against methotrexate-induced injury in rat testis

The histopathological evaluation of healing effects of vitamin C administered before methotrexate therapy on testicular injury induced by methotrexate

Influence of Reduced Folate Carrier and Dihydrofolate Reductase Genes on Methotrexate-Induced Cytotoxicity

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