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

Aim 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 toxici...

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Bibliographic Details
Published inLife sciences (1973) Vol. 171; p. 51
Main Authors Ahmed, Amal AM, Selim, Manar AA, El-Sayed, Norhan M
Format Journal Article
LanguageEnglish
Published New York Elsevier BV 15.02.2017
Subjects
Anesthesia
Antioxidants
Apoptosis
Biomarkers
Catalase
Deoxyribonucleic acid
DNA
DNA fragmentation
Epithelium
Immunohistochemistry
Injection
Lamina propria
Lipoic acid
Localization
Methotrexate
Mucositis
Nuclei
Nuclei (cytology)
Oxidative stress
Proliferating cell nuclear antigen
Rats
Rodents
Toxicity
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Summary:Aim 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. Main methods Thirty male Wistar rats were allocated into three groups; control, MTX-treated group subjected to single intraperitoneal injection of MTX (20 mg/kg, i.p.) and LA- treated group treated with daily intraperitoneal injection of LA (10 mg/kg, i.p.) for 5 weeks before MTX injection (20 mg/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. Key findings 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. Significance LA may be suggested to be a prospective candidate to ameliorate MTX-induced oral mucositis.
ISSN:0024-3205
1879-0631