title: Implication of Nrf2/HO-1 pathway in the coloprotective effect of coenzyme Q10 against experimentally induced ulcerative colitis.
abstract: OBJECTIVE
  Given the increased incidence of ulcerative colitis worldwide, the current study was designed to investigate the coloprotective potential of CoQ10 against experimentally induced ulcerative colitis (UC) and specify the implicated mechanisms.
  
  
  METHODS
  Ulcerative colitis was induced by intracolonic instillation of [2 ml, 3% v/v acetic acid (AA)]. Rats in the different experimental groups received CoQ10 (10 or 30 and 100 mg/kg, orally) for eight consecutive days, either in a protective or curative regimen.
  
  
  RESULTS
  Intracolonic AA instillation significantly increased colon/body weight index, colon weight/colon length ratio, clinical evaluation and macroscopic scoring of UC, serum LDH, C-reactive protein and decreased the serum total antioxidant capacity. Colon MDA, TNF-α and calcium content significantly increased as well, with concomitant reduction in colon GSH, SOD, CAT, Nrf2 and HO-1 contents. Moreover, immunohistochemical staining of colon specimen revealed increased expression of caspase-3 with significant histopathological changes. Coenzyme Q10 suppressed the release of inflammatory biomarkers and restored oxidants/antioxidants hemostasis. In a dose-dependent manner, CoQ10 significantly decreased colon/body weight index, colon weight/colon length ratio, clinical evaluation and macroscopic scoring of UC, serum LDH, C-reactive protein, colon MDA, TNF-α, caspase-3 expression and increased the serum total antioxidant capacity. Colon GSH, SOD, CAT, Nrf2 and HO-1 contents significantly increased. Moreover, coenzyme Q10 significantly preserved tissue histopathological architecture. It appears that the coloprotective effect of CoQ10 was calcium-independent.
  
  
  CONCLUSIONS
  Coenzyme Q10 dose-dependently protects against AA-induced UC mainly via modulation of Nrf2/HO-1 and caspase-3 pathways. Antioxidant, anti-inflammatory and anti-apoptotic properties of CoQ10 are implicated in its observed therapeutic benefit.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Delta University, Mansoura, Egypt.
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: Khodir
authors.affiliation: Department of Histology and Cytology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Hoda
authors.initials: H
authors.lastname: Atef
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. emansaid@mans.edu.eg.
authors.forename: Eman
authors.initials: E
authors.lastname: Said
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Delta University, Mansoura, Egypt.|Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
authors.forename: Hassan A
authors.initials: HA
authors.lastname: ElKashef
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Salem
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000819:agonists / Q000378:metabolism*; D020011:Protective Agents / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D020011:Protective Agents; D014451:Ubiquinone; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C024989:coenzyme Q10
keywords: Caspase-3; Coenzyme Q10; HO-1; Nrf2; TNF-α; Ulcerative colitis