title: Preconditioning with Azadirachta indica ameliorates cardiorenal dysfunction through reduction in oxidative stress and extracellular signal regulated protein kinase signalling.
abstract: BACKGROUND
  Azadirachta indica is widely distributed in Africa, Asia and other tropical parts of the world. A. indica (AI) is traditionally used for the treatment of several conditions including cancer, hypertension, heart diseases and skin disorders. Intestinal ischaemia-reperfusion is a common pathway for many diseases and may lead to multiple organ dysfunction syndrome and death.
  
  
  OBJECTIVE
  In this study, we investigated the ameliorative effects of AI on intestinal ischaemia-reperfusion injury-induced cardiorenal dysfunction.
  
  
  METHODS
  Sixty rats were divided into 6 groups; each containing 10. Corn oil was orally administered to group A (control) rats for 7 days without intestinal ischaemia-reperfusion injury. Group B underwent intestinal ischaemia-reperfusion injury (IIRI) without any pre-treatment. Groups C, D, E and F were pre-treated orally for 7 days with 100 mg/kg AI (100 and (200 mg/kg) vitamin C (100 and 200 mg/kg) respectively and thereafter underwent IIRI on the 8th day.
  
  
  RESULTS
  The cardiac and renal hydrogen peroxide increased significantly whereas serum xanthine oxidase and myeloperoxidase levels were significantly elevated (p < 0.05) in IIRI only when compared to the control. The cardiac and renal reduced glutathione, glutathione peroxidase, protein thiol, non-protein thiol and serum nitric oxide (NO) decreased (p < 0.05) significantly following IIRI. Immunohistochemical evaluation of cardiac and renal tissues showed reduced expressions of the extracellular signal regulated kinase (ERK1/2) in rats with IIRI only. However, pre-treatment with A. indica and vitamin C significantly reduced markers of oxidative stress and inflammation together with improvement in antioxidant status. Also, reduced serum NO level was normalised in rats pre-treated with A. indica and vitamin C with concomitant higher expressions of cardiac and renal ERK1/2.
  
  
  CONCLUSIONS
  Together, A. indica and vitamin C prevented IRI-induced cardiorenal dysfunction via reduction in oxidative stress, improvement in antioxidant defence system and increase in the ERK1/2 expressions. Therefore, A. indica can be a useful chemopreventive agent in the prevention and treatment of conditions associated with intestinal ischaemia-reperfusion injury.
authors.affiliation: Department of Veterinary Medicine, Faculty of Veterinary Medicine, University of Ibadan, Nigeria.
authors.forename: Temidayo Olutayo
authors.initials: TO
authors.lastname: Omóbòwálé
authors.affiliation: Departments of Veterinary Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, University of Ibadan, Nigeria. Electronic address: ademola.oyagbemi778@gmail.com.
authors.forename: Ademola Adetokunbo
authors.initials: AA
authors.lastname: Oyagbemi
authors.affiliation: Department of Veterinary Medicine, Faculty of Veterinary Medicine, University of Ibadan, Nigeria.
authors.forename: Olumuyiwa Abiola
authors.initials: OA
authors.lastname: Adejumobi
authors.affiliation: Department of Veterinary Medicine, Faculty of Veterinary Medicine, University of Ibadan, Nigeria.
authors.forename: Eguonor Vivian
authors.initials: EV
authors.lastname: Orherhe
authors.affiliation: Department of Veterinary Surgery and Reproduction, Faculty of Veterinary Medicine, University of Ibadan, Nigeria.
authors.forename: Adetayo Sadudeen
authors.initials: AS
authors.lastname: Amid
authors.affiliation: Departments of Veterinary Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, University of Ibadan, Nigeria.
authors.forename: Adeolu Alex
authors.initials: AA
authors.lastname: Adedapo
authors.affiliation: Department of Veterinary Medicine, Faculty of Veterinary Medicine, University of Ibadan, Nigeria.
authors.forename: Helen Olubukola
authors.initials: HO
authors.lastname: Nottidge
authors.affiliation: Department of Environmental and Interdisciplinary Sciences, College of Science, Technology and Engineering, Texas Southern University, 3100 Cleburne Avenue, Houston, TX 77004, USA.
authors.forename: Momoh Audu
authors.initials: MA
authors.lastname: Yakubu
keywords: Azadirachta indica; Chemoprevention; Intestinal ischaemia-reperfusion injury; Oxidative stress; Vitamin C