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Mitigating peroxynitrite mediated mitochondrial dysfunction in aged rat brain by mitochondria-targeted antioxidant MitoQ

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Abstract

Although reactive oxygen species mediated oxidative stress is a well-documented mechanism of aging, recent evidences indicate involvement of nitrosative stress in the same. As mitochondrial dysfunction is considered as one of the primary features of aging, the present study was designed to understand the involvement of nitrosative stress by studying the impact of a mitochondria-targeted antioxidant MitoQ, a peroxynitrite (ONOO−) scavenger, on mitochondrial functions. Four groups of rats were included in this study: Group I: Young—6 months (-MitoQ), Group II: Aged—22 months (− MitoQ), Group III: Young—6 months (+ MitoQ), Group IV: Aged—22 months (+ MitoQ). The rats belonging to group III and IV were treated with oral administration of MitoQ (500 μM) daily through drinking water for 5 weeks. MitoQ efficiently suppressed synaptosomal lipid peroxidation and protein oxidation accompanied by diminution of nitrite production and protein bound 3-nitrotyrosine. MitoQ normalized enhanced caspase 3 and 9 activities in aged rat brains and efficiently reversed ONOO− mediated mitochondrial complex I and IV inhibition, restored mitochondrial ATP production and lowered mitochondrial membrane potential loss. To ascertain these findings, a mitochondrial in vitro model (iron/ascorbate) was used involving different free radical scavengers and anti-oxidants. MitoQ provided better protection compared to mercaptoethylguanidine, N-nitro-l-arginine-methyl ester and superoxide dismutase establishing the predominancy of ONOO− in the process compared to •NO and O •−2 . These results clearly highlight the involvement of nitrosative stress in aging process with MitoQ having therapeutic potential to fight against ONOO− mediated aging deficits.

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Acknowledgements

The authors thank Department of Zoology, Jhargram Raj College, West Bengal, India and Department of Zoology, University of Burdwan, West Bengal, India, Pin-741235 for providing permission and laboratory assistance for smooth running of the project. Our sincere thanks to Department of Zoology, Jhargram Raj College, West Bengal, India for funding this project work.

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  1. Department of Biological Sciences, School of Basic and Applied Sciences, Dayananda Sagar University, Shavige Malleshwara Hills, Kumaraswamy Layout, Bengaluru, 560078, India

    Arpan Kumar Maiti & B. C. Spoorthi

  2. The University of Burdwan, Rajbati, Burdwan, West Bengal, 713104, India

    Nimai Chandra Saha

  3. Department of Zoology, University of Kalyani, Kalyani, West Bengal, 741235, India

    Ashis Kumar Panigrahi

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  1. Arpan Kumar Maiti
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Correspondence to Arpan Kumar Maiti.

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Maiti, A.K., Spoorthi, B.C., Saha, N.C. et al. Mitigating peroxynitrite mediated mitochondrial dysfunction in aged rat brain by mitochondria-targeted antioxidant MitoQ. Biogerontology 19, 271–286 (2018). https://doi.org/10.1007/s10522-018-9756-6

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