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

Abstract

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 Ca2 + 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.

Keywords

• Doxorubucin
• Lung
• Oxidative stress
• Transient receptor potential melastatin 2
• Vitamin D

D vitamininin sıçanlarda doksorubisin kaynaklı akciğer hasarı ve TRPM2 immünoreaktivitesi üzerindeki etkileri

Öz

Amaç: Doksorubusin (DOX), yaygın olarak kullanılan bir kemoterapötik ajan olmasına rağmen, birçok organda önemli toksik yan etkilere sebep olmaktadır. Bu çalışma, D vitamininin (VD), DOX ile indüklenen akciğer hasarı ve Ca2+ geçirgen katyon kanalı olan, geçici reseptör potansiyeli melastatin 2 (TRPM2) ekspresyonuna etkilerini araştırmayı amaçlamaktadır. Yöntemler: 24 Wistar albino sıçan dört eşit gruba ayrıldı. Kontrol grubu; hiçbir uygulama yapılmadı. VD grubu; 14 gün boyunca oral damlalıkla (o.d.) 200 IU/kg VD uygulandı. DOX grubu; 8. günde tek doz 10 mg/kg DOX intraperitoneal (i.p.) olarak uygulandı. DOX + VD grubu; 14 gün boyunca o.d. ile 200 IU/kg VD uygulandı, 8. günde tek doz 10 mg/kg DOX i.p. olarak uygulandı. Deney sonunda tüm sıçanlardan akciğer ve serum örnekleri toplandı. Akciğer doku kesitlerine Masson'un trikrom boyama yöntemi ve streptavidin-biotin-peroksidaz kompleks yöntemi uygulandı. Serum toplam antioksidan seviyesi (TAS) ve toplam oksidan seviyesi (TOS) enzime bağlı immünosorbent testi (ELİSA) yöntemi ile değerlendirildi. Bulgular: DOX grubunda kontrol grubuna göre histopatolojik hasar gözlenirken, biyokimyasal ve immünohistokimyasal değerlendirmede, TOS düzeyinin ve TRPM2 ekspresyonunun anlamlı olarak arttığı, TAS düzeyinin ise anlamlı olarak azaldığı saptandı (P<0,001). Diğer taraftan, VD uygulamasının, DOX grubuna kıyasla, DOX+ VD grubunda bu değerleri önemli ölçüde tersine çevirdiği gözlendi (P<0,001). Sonuç: VD, DOX'un neden olduğu akciğer hasarı üzerinde koruyucu bir etki gösterdi. Verilerimiz ayrıca, TRPM2 kanalının DOX ile indüklenen akciğer hasarının patofizyolojisinde bir rolü olabileceğini düşündürmektedir.

Anahtar Kelimeler

• Doksorubusin
• Akciğer
• Oksidatif stres
• Geçici reseptör potansiyeli melastatin 2
• D vitamini

Kaynakça

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