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

  • Arpan Kumar Maiti
  • B. C. Spoorthi
  • Nimai Chandra Saha
  • Ashis Kumar Panigrahi
Research Article

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.

Keywords

Mitochondrial electron transport chain MitoQ Aging Peroxynitrite Nitrosative stress 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors of this paper declare that there is no conflict of interest.

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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Arpan Kumar Maiti
    • 1
  • B. C. Spoorthi
    • 1
  • Nimai Chandra Saha
    • 2
  • Ashis Kumar Panigrahi
    • 3
  1. 1.Department of Biological Sciences, School of Basic and Applied SciencesDayananda Sagar UniversityBengaluruIndia
  2. 2.The University of BurdwanBurdwanIndia
  3. 3.Department of ZoologyUniversity of KalyaniKalyaniIndia

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