Vitamin B12 suppresses GADD153, prevents apoptosis and regulates the testicular function in methotrexate treated rat testis

Karabulut D., Öztürk E., Kaymak E., Kuloglu N., Akin A. T., Yakan B.

BIOTECHNIC & HISTOCHEMISTRY, cilt.97, sa.4, ss.290-297, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 97 Sayı: 4
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1080/10520295.2021.1962976
  • Dergi Adı: BIOTECHNIC & HISTOCHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.290-297
  • Anahtar Kelimeler: Apoptosis, Cx43, GADD153, methotrexate, PCNA, rat, testis, vitamin B12
  • Erciyes Üniversitesi Adresli: Evet

Özet

Methotrexate (MTX) is an anti-neoplastic drug that also causes testicular damage. Vitamin B12 (Vit B12) is a water soluble vitamin that is required for normal metabolism. We investigated Vit B12 as a possible protective agent against testicular damage caused by MTX treatment. We divided rats into four groups: control group, Vit B12 group treated with Vit B12 daily for 15 days, MTX group treated with MTX on day 8, MTX + Vit B12 group treated with MTX on day 8 + Vit B12 for 15 days. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were measured. We also measured proliferating cell nuclear antigen (PCNA), connexin43 (Cx43) and the growth arrest- and DNA damage-inducible gene, 153 (GADD153), using immunohistochemical staining. Apoptosis was assessed using TUNEL staining. The MTX group exhibited degeneration of seminiferous tubules; decreased serum testosterone, LH and FSH levels; fewer PCNA positive cells; increased Cx43 expression; and increased GADD153 and TUNEL stained cells compared to the control group. These pathologic findings were substantially reversed In the MTX + Vit B12 group. MTX caused increased endoplasmic reticulum stress and apoptosis via GADD153. Consequently, Vit B12 potentially is a protective agent against damage caused by MTX.