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Histomorphological and immunohistochemical study of dacomitinib-induced ileal mucositis in rats with the possible protection by baicalin
Samah Kandeel1, Remon S Estfanous2
1 Department of Histology and Cell Biology, Faculty of Medicine, Tanta University, Tanta, Egypt
2 Department of Anatomy and Embryology, Faculty of Medicine, Tanta University, Tanta, Egypt
Correspondence Address:
Samah Kandeel,
Department of Histology and Cell Biology, Faculty of Medicine, Tanta University, El-Geish Street, Postal No. 31527, Tanta
Egypt
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/jmau.jmau_115_20
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Introduction: Gastrointestinal (GIT) mucositis is a common problem associated with chemotherapy. Dacomitinib is a chemotherapeutic drug that treats nonsmall cell lung cancer. It irreversibly binds to the receptors at the ileal epithelial cells, leading to mucosal injury. Baicalin (BA) is a flavonoid with anti-inflammatory, antifibrosis, and antibarrier disruption properties. Aim: This work aimed to investigate the possible protective effects of BA on dacomitinib-induced ileal mucositis in rats by histological and immunohistochemical studies. Materials and Methods: 60 Wistar rats (8–12 weeks) were used (180–200 g) and divided into 6 groups (10 rats each). Group 1: Control; Group 2 (dacomitinib): Rats received dacomitinib 7.5 mg/kg/day orally; Group 3 (dacomitinib + carboxyl methylcellulose [CMC]): Rats received dacomitinib 7.5 mg/kg/day and 0.5% CMC orally; Group 4 (dacomitinib + BA low dose): Rats received low-dose BA 30 mg/kg/day and 7.5 mg/kg/day dacomitinib orally; Group 5 (dacomitinib + BA mid dose): Rats received mid-dose BA 60 mg/kg/day and 7.5 mg/kg/day dacomitinib orally; Group 6 (dacomitinib + BA high dose): Rats received high-dose BA 100 mg/kg/day and 7.5 mg/kg/day dacomitinib orally. Results: Dacomitinib group showed short villi, desquamated epithelium, congested blood vessels, inflammatory cellular infiltrations, dilated lacteals, and wide spaces between the crypts. There is a significant increase in collagen fibers and number of tumor necrosis factor-alpha and proliferating cell nuclear antigen-positive cells. Further, there were lost epithelial cadherin (E-cadherin) and epidermal growth factor receptor immunohistochemical reaction. The previous findings were ameliorated by BA in a dose-dependent manner. Conclusion: BA has a protective effect through its anti-inflammatory, antifibrosis, and antibarrier disruption effects. Hence, BA is considered as a promising new drug for the treatment of chemotherapy-associated GIT problems, especially dacomitinib.
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