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Secoisolariciresinol diglucoside attenuates cardiac hypertrophy and oxidative stress in monocrotaline-induced right heart dysfunction

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Abstract

Pulmonary arterial hypertension (PAH) occurs when remodeling of pulmonary vessels leads to increased pulmonary vascular resistance resulting in increased pulmonary arterial pressure. Increased pulmonary arterial pressure results in right ventricle hypertrophy and eventually heart failure. Oxidative stress has been implicated in the pathogenesis of PAH and may play a role in the regulation of cellular signaling involved in cardiac response to pressure overload. Secoisolariciresinol diglucoside (SDG), a component from flaxseed, has been shown to reduce cardiac oxidative stress in various pathophysiological conditions. We investigated the potential protective effects of SDG in a monocrotaline-induced model of PAH. Five- to six-week-old male Wistar rats were given a single intraperitoneal injection of monocrotaline (60 mg/kg) and sacrificed 21 days later where heart, lung, and plasma were collected. SDG (25 mg/kg) was given via gavage as either a 21-day co-treatment or pre-treatment of 14 days before monocrotaline administration and continued for 21 days. Monocrotaline led to right ventricle hypertrophy, increased lipid peroxidation, and elevated plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST). Co-treatment with SDG did not attenuate hypertrophy or ALT and AST levels but decreased reactive oxygen species (ROS) levels and catalase and superoxide dismutase activity compared to the monocrotaline-treated group. Pre-treatment with SDG decreased right ventricle hypertrophy, ROS levels, lipid peroxidation, catalase, superoxide dismutase, and glutathione peroxidase activity and plasma levels of ALT and AST when compared to the monocrotaline group. These findings indicate that pre-treatment with SDG provided better protection than co-treatment in this model of right heart dysfunction, suggesting an important role for SDG in PAH and right ventricular remodeling.

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Acknowledgements

We would like to acknowledge Rayane B. Teixeira, Denise S. Lacerda, Vanessa D. Ortiz, Giana B. Corssac, Dalvana D. Muller, Tania G. Fernandes, and Ana Lucia Hoefel for their technical assistance. Funding from the Canada-Brazil Awards—Joint Research Projects funded by CAPES (Brazilian Government) and the Government of Canada through Foreign Affairs, Trade and Development Canada is greatly acknowledged. SDG was kindly provided by Dr. K. Prasad from the University of Saskatchewan, Canada. S. Puukila was supported by research funding from Bruce Power and NSERC.

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Authors and Affiliations

  1. Department of Biology, Lakehead University, 955 Oliver Road, Thunder Bay, ON, P7B 5E1, Canada

    Stephanie Puukila

  2. Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite 500, Porto Alegre, RS, 90050-170, Brazil

    Rafael Oliveira Fernandes, Patrick Türck, Cristina Campos Carraro, Jéssica Hellen Poletto Bonetto, Bruna Gazzi de Lima-Seolin, Alex Sander da Rosa Araujo & Adriane Belló-Klein

  3. Department of Pediatrics, Sainte-Justine University Hospital Research Center, University of Montreal, 3175 Côte Sainte-Catherine, Montreal, QC, H3T 1C5, Canada

    Rafael Oliveira Fernandes

  4. Northern Ontario School of Medicine, Laurentian University, 935 Ramsey Lake Road, Sudbury, ON, P3E 2C6, Canada

    Douglas Boreham

  5. Medical Sciences Division, Northern Ontario School of Medicine, Lakehead University, 955 Oliver Road, Thunder Bay, ON, P7B 5E1, Canada

    Neelam Khaper

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  1. Stephanie Puukila
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Correspondence to Neelam Khaper.

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Puukila, S., Fernandes, R.O., Türck, P. et al. Secoisolariciresinol diglucoside attenuates cardiac hypertrophy and oxidative stress in monocrotaline-induced right heart dysfunction. Mol Cell Biochem 432, 33–39 (2017). https://doi.org/10.1007/s11010-017-2995-z

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