title: The protective effect of hesperidin on methotrexate-induced intestinal epithelial damage in rats: an experimental study.
abstract: OBJECTIVE
  The purpose of this experimental study was to evaluate the efficacy of hesperidin (HES) in protecting against methotrexate (MTX)-induced intestinal damage using histopathological and immunohistochemical techniques.
  
  
  METHODS
  Seventy-eight male Wistar albino rats were divided into 4 groups that received (a) saline only (control group), n = 19; (b) HES only, n = 19; (c) MTX only, n = 19, and (d) MTX plus HES, n = 21. On the first day of the study, a single dose of MTX (20 mg/kg) was administered intraperitoneally to group 3 and 4 rats. The HES (200 mg/kg) was administered by gavage for 5 days. For the MTX plus HES group, HES (200 mg/kg) was administered by gavage for 5 days after MTX treatment. Rats were sacrificed on the 2nd, 4th and 6th day of the study. Tissue samples from the jejunum were taken for histopathological and immunohistochemical analysis.
  
  
  RESULTS
  On the 4th day, crypt injury in the MTX plus HES group (1.00 ± 0.00) was less than that in the MTX group (2.00 ± 0.89; p < 0.05). The small intestinal damage score was lower in the MTX plus HES group (6.33 ± 0.82) as compared to the MTX group (8.00 ± 2.37). Inducible nitric oxide synthase and interleukin-8 levels were lower in the MTX plus HES group (65 and 25%, respectively) as compared to the corresponding values of the MTX group (80 and 52.5%, respectively). On the 6th day, the Ki-67 proliferation index in the MTX group (45%) was lower than that in the MTX plus HES group (76.67%) and the control group (p < 0.05). The small intestinal damage score was high in the HES group on the 4th day due to increased cellular infiltration. On the 6th day, the Ki-67 proliferation index rose in parallel with the decrease in cellular infiltration and therefore histopathological scoring. The proliferation-enhancing effect of HES also appeared in healthy rats.
  
  
  CONCLUSIONS
  HES seemed to have a protective effect against MTX-induced intestinal injury.
authors.affiliation: Department of Pediatric Hematology/Oncology, Faculty of Medicine, Cukurova University, Adana, Turkey.
authors.forename: Can
authors.initials: C
authors.lastname: Acipayam
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Bayram
authors.forename: Kenan
authors.initials: K
authors.lastname: Daglioglu
authors.forename: Figen
authors.initials: F
authors.lastname: Doran
authors.forename: Sema
authors.initials: S
authors.lastname: Yilmaz
authors.forename: Gülay
authors.initials: G
authors.lastname: Sezgin
authors.forename: Berna
authors.initials: B
authors.lastname: Totan Ateş
authors.forename: Ayşe
authors.initials: A
authors.lastname: Ozkan
authors.forename: Atila
authors.initials: A
authors.lastname: Tanyeli
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006569:Hesperidin / Q000008:administration & dosage / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D005765:Gastrointestinal Agents; D016209:Interleukin-8; D019394:Ki-67 Antigen; D006569:Hesperidin; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D008727:Methotrexate