α-Lipoic acid ameliorates oral mucositis and oxidative stress induced by methotrexate in rats. Histological and immunohistochemical study

Oral mucositis is a common adverse effect of Methotrexate (MTX) that may limit its clinical use. Oxidative stress and apoptosis have been proposed to mediate MTX toxicity. The current study was conducted to assess the conceivable protective effect of α-lipoic acid (LA) against MTX induced toxicity on both buccal and lingual mucosae.Thirty male Wistar rats were allocated into three groups; control, MTX-treated group subjected to single intraperitoneal injection of MTX (20mg/kg, i.p.) and LA- treated group treated with daily intraperitoneal injection of LA (10mg/kg, i.p.) for 5weeks before MTX injection (20mg/kg, i.p.). Rats were then sacrificed under anesthesia then their buccal and lingual mucosae were dissected out and processed for biochemical and histopathological studies. Biomarkers of oxidative stress and integrity of nuclear DNA (nDNA) were estimated. Immunostaining was used to determine Bax and PCNA localization.MTX-treated rats showed increased levels of MDA and fragmentation of DNA in addition to reduction of GSH levels and activities of catalase and SOD. Histological examination of MTX-treated rats demonstrated degenerative changes that involved the surface epithelium and lamina propria of their buccal and lingual mucosae. Immunohistochemical results of MTX-treated rats revealed strongly positive Bax and weakly positive PCNA staining reactivity of the nuclei of the basal and parabasal cells of the surface epithelium. However, LA significantly attenuated MTX-evoked alterations in the previous-stated parameters highlighting its antioxidant and anti-apoptotic potential.LA may be suggested to be a prospective candidate to ameliorate MTX-induced oral mucositis.