Nebivolol to attenuate the effects of hyper-homocysteinaemia in rats

Atherosclerosis. 2015 May;240(1):33-9. doi: 10.1016/j.atherosclerosis.2015.02.054. Epub 2015 Feb 28.

Abstract

Objective: This study investigated the prophylactic effect of nebivolol against hyper-homocysteinaemia (hHcy) induced oxidative stress in brain, heart, liver and kidney tissues and histomorphometric changes in the thoracic aorta.

Methods: Twenty-four adult male Wistar rats were divided into a control, nebivolol, hHcy and nebivolol+hHcy group. hHcy was induced by oral administration of L-methionine (1 g/kg/day) for 28 days. 10 mg/kg/day nebivolol was administered orally for 28 days. Malondialdehyde (MDA) and glutathione (GSH) levels and catalase (CAT) and superoxide dismutase (SOD) activities in the tissues were determined. The total cross-sectional area (TCSA), luminal cross-sectional area (LCSA) and intima-media thickness (IMT) were measured in the thoracic aorta.

Results: Homocysteine (Hcy) levels were lower in the nebivolol+hHcy group than in the hHcy group. Nebivolol treatment significantly decreased high MDA levels in the brain, heart and liver tissues. The level of GSH was higher in the brain, heart and kidney tissues of the nebivolol+hHcy group (P<0.001). The activity of CAT increased only in the kidney tissue of the nebivolol+hHcy group (P<0.01), and the activity of SOD was significantly increased in all the tissues in this group. Increased TCSA and IMT in the nebivolol+hHcy group were significantly decreased after nebivolol administration. The LCSA was significantly higher in the hHcy group than the control group, probably due to outward vascular remodelling.

Conclusion: Nebivolol treatment may be useful in different clinical scenarios where hHcy affects physiopathological pathways.

Keywords: Aorta; Hyper-homocysteinaemia; Nebivolol; Oxidant/anti-oxidant parameters; Rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / pathology
  • Biomarkers / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Catalase / metabolism
  • Cytoprotection
  • Disease Models, Animal
  • Glutathione / metabolism
  • Hyperhomocysteinemia / chemically induced
  • Hyperhomocysteinemia / complications
  • Hyperhomocysteinemia / drug therapy*
  • Kidney / drug effects
  • Kidney / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Methionine
  • Myocardium / metabolism
  • Nebivolol / pharmacology*
  • Oxidative Stress / drug effects*
  • Rats, Wistar
  • Superoxide Dismutase / metabolism
  • Time Factors
  • Vascular Remodeling / drug effects

Substances

  • Antioxidants
  • Biomarkers
  • Nebivolol
  • Malondialdehyde
  • Methionine
  • Catalase
  • Superoxide Dismutase
  • Glutathione