Vitamin D: An effective way to combat methotrexate-induced testis injury

Yalcin, Alper; Aydın, Hasan Emre; Türk, Ahmet; Doğukan, Mevlüt; Eser, Nadire; Onderci, Muhittin; Üçkardeş, Fatih; Yoldaş, Atila; Yılmaz, Erkan; Keleş, Hikmet

doi:10.5455/medscience.2020.10.222

Cited by 9 publications

(6 citation statements)

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“…Of note in our study, patients with sacroiliitis were not treated with MTX according to European and American recommendations. There are no published data on MTX survival in PsA patients with different statuses of vitamin D. Few authors have described a higher rate of adverse events (such as mucositis and testis injuries) in the case of insufficient levels of vitamin D [ 40 , 41 ], but we did not observe differences in the occurrence of adverse events in the groups of PsA patients with diverse statuses of vitamin D.…”

Section: Discussioncontrasting

confidence: 85%

Vitamin D Status and Psoriatic Arthritis: Association with the Risk for Sacroiliitis and Influence on the Retention Rate of Methotrexate Monotherapy and First Biological Drug Survival—A Retrospective Study

Rotondo

Cantatore

Cici

et al. 2023

IJMS

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A growing body of evidence on the importance of vitamin D in immune modulation has increased the interest in its possible impact on the course of rheumatological diseases. The scope of our study is to assess if the presence of different statuses of vitamin D could interfere in the clinical subsets, in methotrexate monotherapy discontinuation, and biological drug (b-DMARDs) survival in psoriatic arthritis patients (PsA). We conducted a retrospective study on PsA patients and split them into three groups based on their vitamin D status: the group with 25(OH)D ≤ 20 ng/mL, the group with levels of 25(OH)D between 20 and 30 ng/mL, and the group with serum levels of 25(OH)D ≥ 30 ng/mL. All patients were required to fulfill the CASPAR criteria for psoriatic arthritis and to have the evaluation of vitamin D serum levels at baseline visit and at clinical follow-up visits. The exclusion criteria were ages less than 18 years old, the presence of HLA B27, and satisfaction of rheumatoid arthritis classification criteria (during the study time). Statistical significance was set at p ≤ 0.05. Furthermore, 570 patients with PsA were screened and 233 were recruited. A level of 25(OH)D ≤ 20 ng/mL was present in 39% of patients; levels of 25(OH)D between 20 and 30 ng/mL presented in 25% of patients; 65% of patients with sacroiliitis presented 25 (OH)D ≤ 20 ng/mL. Methotrexate monotherapy discontinuation for failure was higher in the group with 25 (OH)D ≤ 20 ng/mL (survival time: 92 ± 10.3 weeks vs. 141.9 ± 24.1 weeks vs. 160.1 ± 23.6 weeks; p = 0.02) with higher discontinuation risk (HR = 2.168, 95% CI 1.334, 3.522; p = 0.002) than those with 25(OH)D between 20 and 30 ng/mL and those with 25(OH)D ≥ 30 ng/mL. Significantly shorter survival of first b-DMARDs was assessed in the group with 25 (OH)D ≤ 20 ng/mL versus the other groups (133.6 ± 11 weeks vs. 204.8 ± 35.8 weeks vs. 298.9 ± 35.4; p = 0,028) (discontinuation risk 2.129, 95% CI 1.186, 3.821; p = 0.011). This study highlights significant differences in clinical presentation, in particular sacroiliac involvement and on drug survival (methotrexate and b-DMARDs) in PsA patients with vitamin D deficiency. Further prospective studies, including a larger sample of patients, are needed to validate these data and to assess if the supplementation of vitamin D could improve the b-DMARDs response in PsA patients.

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Section: Discussioncontrasting

confidence: 85%

Vitamin D Status and Psoriatic Arthritis: Association with the Risk for Sacroiliitis and Influence on the Retention Rate of Methotrexate Monotherapy and First Biological Drug Survival—A Retrospective Study

Rotondo

Cantatore

Cici

et al. 2023

IJMS

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“…These histopathological changes come in agreement with previous studies which reported that MTX induces degeneration and atrophy of seminiferous tubules, sloughing of germ cells away from the basal lamina, decrease in quantity and quality of sperms, and severe apoptosis in the germinal epithelium [ 19 , 21 , 22 ]. Damage to the germinal epithelium resulted in a significant decrease in the Johnson score; the same was found by [ 21 , 23 ].…”

Section: Discussionsupporting

confidence: 76%

Therapeutic Effect of Stem Cells on Male Infertility in a Rat Model: Histological, Molecular, Biochemical, and Functional Study

Mohammed

Mansour

Salem

2021

Stem Cells International

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Methotrexate (MTX) is a folic acid antagonist, widely used as a chemotherapeutic and immunosuppressive drug, but it is toxic to reproductive systems. In recent years, the era of stem cell applications becomes a promising point as a possible therapeutic agent in male infertility. This study is aimed at evaluating the therapeutic effects of stem cells at histological, molecular, biochemical, and functional levels in a methotrexate-induced testicular damage model. Material and Methods. Thirty rats were divided randomly into three groups (ten rats each): group 1 (control): animals received an intraperitoneal injection of 2 ml phosphate-buffered saline per week for 4 weeks, group 2 (MTX-treated group): animals were intraperitoneally injected with methotrexate (8 mg/kg) once weekly for 4 weeks, and group 3 (ADMSC-treated group): methotrexate-treated animals received a single dose of 1 × 10 6 stem cells/rat at the 5th week. At the 8th week, blood samples were collected for hormonal analysis; then, animals were sacrificed. The testes were dissected; the right testis was stained with hematoxylin and eosin. Random sections were taken from group 3 and examined with a fluorescent microscope. The left testis was divided into two specimens: the first was used for an electron microscope and the second was homogenized for molecular and biochemical assessments. Results. Group 2 showed significant histological changes, decreased free testosterone level, decrease in stem cell factor expression, and dysfunction of the oxidation state. The results revealed significant improvement of these parameters. Conclusion. Transplantation of adipose tissue-derived stem cells (ADMSCs) can improve the testicular damage histologically and functionally in a rat model.

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“…VD is effective on the protection of pulmonary injury and tissue repair [19], and in preventing oxidative stress [20]. In this study, VD administration exhibited ameliorative utility by reversing the tissue structure, similar to the control group, as VD reduces tissue injury [21].…”

Section: Discussionmentioning

confidence: 62%

Effects of Vitamin D on doxorubucin-induced lung injury and TRPM2 immunoreactivity in rats

Yalcin¹,

Türk²,

Aydın³

et al. 2020

Journal of Surgery and Medicine

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Aim: Although doxorubicin (DOX) is a commonly used chemotherapeutic agent, it causes significant toxic side effects on many organs. This study aims to investigate the effects of vitamin D (VD) on DOX-induced lung injury and expression of transient receptor potential melastatin 2 (TRPM2), a Ca 2 + permeable cation channel. Methods: A total of 24 Wistar albino rats were separated into four groups of six rats, as follows: The control group received no medications. The VD group received 200 IU/kg VD via an oral dropper (o.d.) for 14-days. DOX group received a single dose of 10 mg/kg DOX intraperitoneally (i.p.) on day 8. DOX+VD group was administered 200 IU/kg VD via an o.d. for 14-days, and a single dose of 10 mg/kg DOX i.p. on day 8. At the end of the experiment, lung and serum samples from all rats were collected. Masson's trichrome staining and streptavidin-biotin-peroxidase complex were applied to the lung tissue sections. Serum total antioxidant status (TAS) and total oxidant status (TOS) were assessed by enzyme-linked immunosorbent assay (ELISA) method. Results: Histopathological damage was observed in the DOX group compared to the control group, and biochemical and immunohistochemical evaluation revealed that TOS level and TRPM2 expression increased while TAS level decreased significantly (P<0.001). Additionally, compared to the DOX group VD administration significantly reversed these values in the DOX+VD group (P<0.001). Conclusion: VD showed a protective effect on lung damage induced by DOX. Our data also suggest that TRPM2 channel may have a role in the pathophysiology of DOX-induced lung damage.

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Vitamin D: An effective way to combat methotrexate-induced testis injury

Cited by 9 publications

References 0 publications

Vitamin D Status and Psoriatic Arthritis: Association with the Risk for Sacroiliitis and Influence on the Retention Rate of Methotrexate Monotherapy and First Biological Drug Survival—A Retrospective Study

Vitamin D Status and Psoriatic Arthritis: Association with the Risk for Sacroiliitis and Influence on the Retention Rate of Methotrexate Monotherapy and First Biological Drug Survival—A Retrospective Study

Therapeutic Effect of Stem Cells on Male Infertility in a Rat Model: Histological, Molecular, Biochemical, and Functional Study

Effects of Vitamin D on doxorubucin-induced lung injury and TRPM2 immunoreactivity in rats

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