title: Protective effects of silymarin on epirubicin-induced mucosal barrier injury of the gastrointestinal tract.
abstract: Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the protective effects of silymarin on epirubicin-induced mucosal barrier injury in CD-1 mice. Immunohistochemical activity of both pro-apoptotic Bax and anti-apoptotic Bcl-2 markers, together with p53, cyt-P450 expression and DNA damage analysis on stomach, small intestine and colon were evaluated. Our results indicated stronger expression for cyt P450 in all analyzed gastrointestinal tissues of Epi group, which demonstrate intense drug detoxification. Bax immunopositivity was intense in the absorptive enterocytes and lamina connective cells of the small intestine, surface epithelial cells of the stomach and also in the colonic epithelium and lamina concomitant with a decreased Bcl-2 expression in all analyzed tissues. Epirubicin-induced gastrointestinal damage was verified by a goblet cell count and morphology analysis on histopathological sections stained for mucins. In all analyzed tissues, Bax immunopositivity has been withdrawn by highest dose of silymarin concomitant with reversal of Bcl-2 intensity at a level comparable with control. p53 expression was found in all analyzed tissues and decreased by high dose of silymarin. Also, DNA internucleosomal fragmentation was observed in the Epi groups for all analyzed tissues was almost suppressed at 100 mg/kg Sy co-treatment. Histological aspect and goblet cell count were restored at a highest dose of Sy for both small and large intestine. In conclusion, our findings suggest that silymarin may prevent cellular damage of epirubicin-induced toxicity and was effective in reducing the severity indicators of gastrointestinal mucositis in mice.
authors.affiliation: a Department of Hematology, Faculty of Medicine , Pharmacy and Dentistry, Vasile Goldis Western University of Arad , Arad , Romania .
authors.forename: Alciona
authors.initials: A
authors.lastname: Sasu
authors.affiliation: b Institute of Life Sciences, Vasile Goldis Western University of Arad , Arad , Romania .
authors.forename: Hildegard
authors.initials: H
authors.lastname: Herman
authors.affiliation: c Department of Histology , and.
authors.forename: Teodora
authors.initials: T
authors.lastname: Mariasiu
authors.affiliation: b Institute of Life Sciences, Vasile Goldis Western University of Arad , Arad , Romania .
authors.forename: Marcel
authors.initials: M
authors.lastname: Rosu
authors.affiliation: b Institute of Life Sciences, Vasile Goldis Western University of Arad , Arad , Romania .
authors.forename: Cornel
authors.initials: C
authors.lastname: Balta
authors.affiliation: c Department of Histology , and.
authors.forename: Nicoleta
authors.initials: N
authors.lastname: Anghel
authors.affiliation: d Department of Gastroenterology, Faculty of Medicine , Pharmacy and Dentistry, Vasile Goldis Western University of Arad , Arad , Romania.
authors.forename: Eftimie
authors.initials: E
authors.lastname: Miutescu
authors.affiliation: a Department of Hematology, Faculty of Medicine , Pharmacy and Dentistry, Vasile Goldis Western University of Arad , Arad , Romania .
authors.forename: Coralia
authors.initials: C
authors.lastname: Cotoraci
authors.affiliation: b Institute of Life Sciences, Vasile Goldis Western University of Arad , Arad , Romania .|c Department of Histology , and.
authors.forename: Anca
authors.initials: A
authors.lastname: Hermenean
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D051379:Mice; D052016:Mucositis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012720:Severity of Illness Index; D012838:Silymarin / Q000008:administration & dosage / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012838:Silymarin; D051028:bcl-2-Associated X Protein; D015251:Epirubicin; D003577:Cytochrome P-450 Enzyme System
keywords: Epirubicin; gastrointestinal tract; mucositis; silymarin