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

Sayılmaz, Aysun; Karabulut, Yasemin Yuyucu; Özgörgülü, Aydan

doi:10.5152/tud.2016.63903

Cited by 12 publications

(8 citation statements)

References 19 publications

(37 reference statements)

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“…In our study, in accordance with literature, seminiferous tubule diameter 7,9-11,48 and germinal epithelial thickness 10,33 in the MTX group decreased significantly, while interstitial field width 34,50 increased significantly. Saxena et al 49 reported that MTX could not replicate the DNA of germinal epithelial cells and significantly decrease the seminiferous tubule cellular content by inhibiting DHFR, the essential enzyme required for DNA synthesis.…”

Section: Discussionsupporting

confidence: 92%

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Protective effect of pyrrolidine dithiocarbamate against methotrexate-induced testicular damage

2021

Hum Exp Toxicol

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The aim of the study was to investigate the protective effect of pyrrolidine dithiocarbamate (PDTC) against methotrexate (MTX)-induced testicular damage in rats. Forty Wistar albino male rats were divided into equally four groups: Control group (saline solution, IP), PDTC group (100 mg/kg PDTC,IP, 10 days), MTX group (20 mg/kg MTX, IP, single dose, on the 6th day) and MTX + PDTC group (100 mg/kg PDTC, IP, 10 days and 20 mg/kg MTX, IP, single dose, on the 6th day). After 10 days, testicular tissues were excised for morphometric, histological and immunohistochemical evaluations. Serum testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH) and prokineticin 2 (PK2) levels were determined. Body and testicular weights were measured. Testicular damage was assessed by histological evaluation. Nuclear factor kappa B (NFkB), nuclear factor erythroid 2 related factor 2 (Nrf2) and PK2 immunoreactivities were evaluated by HSCORE. Body and testicular weights, serum FSH, LH, testosterone levels, seminiferous tubule diameter and germinal epithelial thickness were significantly decreased in the MTX group. However, serum PK2 level, histologically damaged seminiferous tubules and interstitial field width were significantly increased. Additionally, there was an increase in NFkB and PK2 immunoreactivity, whereas there was a significant decrease in Nrf2 immunoreactivity. PDTC significantly improved hormonal, morphometric, histological and immunohistochemical findings. Taken together, we conclude that PDTC may reduce MTX-induced testicular damage via NFkB, Nrf2 and PK2 signaling pathways.

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Section: Discussionsupporting

confidence: 92%

“…[6][7][8] It also causes testicular degeneration. [9][10][11][12] The exact mechanisms of MTX toxicity are still elusive. A well-known mechanism of MTX toxicity is the inhibition of dihydrofolate reductase (DHFR).…”

Section: Introductionmentioning

confidence: 99%

Protective effect of pyrrolidine dithiocarbamate against methotrexate-induced testicular damage

2021

Hum Exp Toxicol

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“…Blocking tetrahydrofolate synthesis by methotrexate stops cell division and protein synthesis. It is known that the cytotoxic effect of MTX on the 'S phase' of the cell cycle is a factor that inhibits cell division (3). Moreover, this cytotoxic effect is not limited to only tumor cells; MTX is known to affect vital organs through endogenous oxidant systems and inflammatory pathways (4).…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Petroselinum crispum (Parsley) Extract Against Methotrexate-Induced Hepatotoxicity

Ertaş¹,

Turan²,

Özbeyli³

et al. 2021

ejb

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Objective: By inhibiting the synthesis of thymidine and purine, and thereby DNA synthesis, Methotrexate (MTX), suppresses the proliferation of cancer cells. It is thought that the side-effect mechanism is related to oxidant molecules derived from MTX metabolism. In this study, we examined whether the Petroselinum crispum extracts (PCr; parsley) of which the antioxidant properties have been previously shown, was protective against MTX induced liver damage.Materials and Methods: Sprague Dawley rats (female/male; 200-250 g) were used. MTX was injected intraperitoneally and PCr extract was given orally. A single dose of 20mg/kg MTX was administered to the groups that were to experience hepatotoxicity. Then, a physiological saline (MTX group) or PCr (2 g/kg, MTX + PCr group) treatment was applied for 5 days. The same treatments were applied to the other groups (control group, PCr group) for 5 days after a single dose saline injection. At the end of the study, the biochemical parameters were examined in the blood and liver tissues taken from animals sacrificed by decapitation.Results: MTX caused a significant increase in malondialdehyde and collagen levels and myeloperoxidase and caspase-3 activities, while glutathione levels were found to have decreased. PCr treatment showed protective efficacy by preventing these increases. Conclusion:It appears that the administration of PCr to MTX treated rats prevented the accumulation of lipid peroxides, inflamatory reactions and depletion of antioxidant glutathione, and thus protected liver tissues against oxidative stress.

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“…As a result of this injury, destruction of the spermatogenic epithelium, changes in the support cell structure, and antioxidant enzyme activities can occur (Wang et al, 2018). Many studies show that the toxic effects of MTX on the testicles are reduced by the use of various antioxidant substances (Akacha et al, 2020; Felemban et al, 2020; Oufi & Al‐Shawi, 2014; Pınar et al, 2018; Sayılmaz et al, 2016; Wang et al, 2018; Yaman et al, 2018; Yuluǧ et al, 2013). Furthermore, omega‐3 fatty acids present in fish oil (FO) have been shown to protect rat testis tissue from oxidative damage (Qi et al, 2017; Uygur et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Effects of fish oil on methotrexate‐induced reproductive damage in rats

et al. 2022

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Methotrexate (MTX) is a folic acid antagonist that is commonly used in paediatric and adult oncology to treat a variety of malignancies. Internal organs, including the testis, are severely cytotoxic and genotoxic to MTX. Omega-3, as an antioxidant, has been shown to protect rat testis tissue from injury. The effect of fish oil (FO) on MTXinduced reproductive damage in rats was investigated in this work. The 28 animals were divided into four groups for this purpose (control, FO, MTX, and MTX-FO). On the third day, the MTX group received a single intraperitoneal injection of 20 mg/kg MTX. Furthermore, in the FO and MTX-FO groups, FO was delivered through gavage once daily for 14 days. All animals euthanized under general anaesthesia on the 15th day. TBARS, catalase, glutathione peroxidase, glutathione (GSH), superoxide dismutase levels were measured biochemically. The Cosentino grading system was utilized for histology. Germ cell thickness and caspase-3 activity were also evaluated. In addition, sperm motility rate, epididymal sperm count, aberrant sperm rate, and sperm vitality were measured to assess sperm quality. Some TBARS levels have increased, but GSH levels decreased significantly in the MTX group. FO reduced TBARS levels while considerably increasing GSH levels. All sperm quality measures were significantly lowered in the MTX group, while FO had a recovery effect. There were no notable variations in histopathology across groups except for germ cell thickness, which reduced considerably in the MTX group and recovered with FO treatment. As a result, FO has been shown to reduce testicular toxicity following MTX treatment in rats.

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

Cited by 12 publications

References 19 publications

Protective effect of pyrrolidine dithiocarbamate against methotrexate-induced testicular damage

Protective effect of pyrrolidine dithiocarbamate against methotrexate-induced testicular damage

Protective Effects of Petroselinum crispum (Parsley) Extract Against Methotrexate-Induced Hepatotoxicity

Effects of fish oil on methotrexate‐induced reproductive damage in rats

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