Histomorphological and Immunohistochemical Study of Dacomitinib-Induced Ileal Mucositis in Rats with the Possible Protection by Baicalin.

Abstract

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. This work aimed to investigate the possible protective effects of BA on dacomitinib-induced ileal mucositis in rats by histological and immunohistochemical studies. 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. 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. 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.