Lapatinib prevents and ameliorates dermal fibrosis in bleomycin induced experimental scleroderma model

Authors : Berçem Afşar Karatepe, Servet Yolbaş, Ahmet Yıldırım, Derya Hoşgün, İbrahim Hanifi Özercan, Ebru Önalan, Süleyman Serdar Koca

Pages : 1-8

Doi:10.58651/jomtu.1404234

View : 54 | Download : 61

Publication Date : 2024-04-30

Article Type : Research Paper

Abstract :Background: Scleroderma is a connective tissue disease characterized by endothelial damage and diffuse interstitial fibrosis. Lapatinib, a tyrosine kinase inhibitor, is a 4-anilinoquinol derivative. It inhibits many important signalling pathways including MAPK and PI3K. As a result, it affects cell cycle progression, apoptosis, angiogenesis and cell adhesion. Materials and Methods: Mice with an average age of 6 weeks and a weight of 20-25 g were divided into 6 equal groups (n=10 in each group). Mice in the control group (group A and group D), which were not treated with bleomycin (BLM), received sc phosphate buffered saline (PBS) daily. BLM was dissolved in FTS and administered to mice in groups B and C for 3 weeks, and to mice in groups E and F at a dose of sc 100 L (100 g) daily for 6 weeks. Mice in groups A, B and C were sacrificed at the end of week 3; mice in groups D, E and F were sacrificed at the end of week 6 and tissue samples were collected for further analysis. The mRNA expressions of TGF-β1 and fibronectin-1 were determined by RT-PCR. Results: Repeated subcutaneous administration of BLM caused dermal inflammatory cell infiltration, increased skin thickness and dermal fibrosis at early and late stages. TGF-β1 and fibronectin-1 mRNA expressions were also evidently increased. In both prophylactic and therapeutic applications of lapatinib, TGF-β1 and fibronectin-1mRNA expressions decreased markedly. In addition, histopathological dermal necro- inflammation and fibrosis were reduced. Conclusions: Lapatinib may exert anti-fibrotic effects in BLM-induced dermal fibrosis model. Studies show that lapatinib is a potential therapeutic agent, but it needs to be confirmed with in vivo studies.
Keywords : Deneysel skleroderma, tirozin kinaz, lapatinib