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Coenzyme Q10, Biochanin A and Phloretin Attenuate Cr(VI)-Induced Oxidative Stress and DNA Damage by Stimulating Nrf2/HO-1 Pathway in the Experimental Model

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Abstract

Hexavalent chromium [Cr(VI)] has emerged as a prevailing environmental and occupational contaminant over the past few decades. However, the knowledge is sparse regarding Cr(VI)-induced neurological aberrations, and its remediation through natural bioactive compounds has not been fully explored. This study intended to probe the possible invigorative effects of nutraceuticals such as coenzyme Q10 (CoQ10), biochanin A (BCA), and phloretin (PHL) on Cr(VI) intoxicated Swiss albino mice with special emphasis on Nrf2/HO-1/NQO1 gene expressions. Mice received potassium dichromate (75 ppm) through drinking water and were simultaneously co-treated intraperitoneally with CoQ10 (10 mg/kg), BCA, and PHL (50 mg/kg) each for 30-day treatment period. The statistics highlight the elevated levels of lipid peroxidation (LPO) and protein carbonyl content (PCC) with a concomitant reduction in the superoxide dismutase (SOD), glutathione-S-transferase (GST), reduced glutathione (GSH), total thiols (TT), catalase (CAT), and cholinesterase activities in the Cr(VI)-exposed mice. The collateral assessment of DNA fragmentation, DNA breakages, and induced histological alterations was in conformity with the above findings in conjugation with the dysregulation in the Nrf2 and associated downstream HO-1 and NQO1 gene expressions. Co-treatment with the selected natural compounds reversed the above-altered parameters significantly, thereby bringing cellular homeostasis in alleviating the Cr(VI)-induced conciliated impairments. Our study demonstrated that the combination of different bioactive compounds shields the brain better against Cr(VI)-induced neurotoxicity by revoking the oxidative stress-associated manifestations. These compounds may represent a new potential combination therapy due to their ability to modulate the cellular antioxidant responses by upregulating the Nrf2/HO-1/NQO1 signaling pathway against Cr(VI)-exposed population.

Highlights

  • Cr(VI)-associated heavy metal exposure poses a significant threat to the environment, especially to living organisms.

  • Cr(VI) exposure for 30 days resulted in the free radical’s generation that caused neurotoxicity in the Swiss albino mice.

  • Natural compounds such as coenzyme Q10, biochanin A, and phloretin counteracted the neurotoxic effect due to Cr(VI) exposure in scavenging of free radicals by enhancing Nrf2/HO-1/NQO1 gene expressions in maintaining the cellular homeostasis.

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Data Availability

All data generated or analyzed during this study are included in this article. Data will be available on request. Correspondence and requests for materials should be addressed to Gyanendra Singh.

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Acknowledgements

The authors are thankful to the Director, ICMR-NIOH Ahmedabad, for providing the necessary infrastructure for conducting this study. The authors acknowledge the help from the Animal House Facility staff in carrying out the study. The authors are also grateful to the Zydus Research Center (ZRC), Ahmedabad, for gifting the Swiss albino mice for the study.

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  1. Swapnil Tripathi and Dharati Parmar contributed equally to this work.

Authors and Affiliations

  1. Toxicology Department, ICMR-National Institute of Occupational Health, Ahmedabad, 380016, India

    Swapnil Tripathi, Dharati Parmar, Shabrin Fathima & Gyanendra Singh

  2. Department of Biochemistry & Forensic Science, Gujarat University, Ahmedabad, 380009, India

    Swapnil Tripathi

  3. College of Veterinary Science and Animal Husbandry, Kamdhenu University, Sardarkrushinagar, 385506, India

    Samir Raval

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  1. Swapnil Tripathi
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Contributions

All authors contributed to the study objectives. Swapnil Tripathi: investigation, visualization, writing — original draft preparation. Shabrin Fhatima: investigation, visualization; Dharati Parmar: investigation, visualization; Samir Raval: investigation, visualization, resources; Gyanendra Singh: conceptualization, visualization, supervision, writing — reviewing and editing. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Gyanendra Singh.

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The present study on animals was conducted as per the compliance with the Institutional Animal Ethics Committee (IAEC) of the ICMR-National Institute of Occupational Health (NIOH), Ahmedabad wide approval no. IAEC/NIOH/2018–19/21/02/M.

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Tripathi, S., Parmar, D., Fathima, S. et al. Coenzyme Q10, Biochanin A and Phloretin Attenuate Cr(VI)-Induced Oxidative Stress and DNA Damage by Stimulating Nrf2/HO-1 Pathway in the Experimental Model. Biol Trace Elem Res 201, 2427–2441 (2023). https://doi.org/10.1007/s12011-022-03358-5

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