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Amelioration of Phytanic Acid–Induced Neurotoxicity by Nutraceuticals: Mechanistic Insights

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Abstract

Phytanic acid (PA) (3,7,11,15-tetramethylhexadecanoic acid) is a methyl-branched fatty acid that enters the body through food consumption, primarily through red meat, dairy products, and fatty marine foods. The metabolic byproduct of phytol is PA, which is then oxidized by the ruminal microbiota and some marine species. The first methyl group at the 3-position prevents the β-oxidation of branched-chain fatty acid (BCFA). Instead, α-oxidation of PA results in the production of pristanic acid (2,10,14-tetramethylpentadecanoic acid) with CO2. This fatty acid (FA) builds up in individuals with certain peroxisomal disorders and is historically linked to neurological impairment. It also causes oxidative stress in synaptosomes, as demonstrated by an increase in the production of reactive oxygen species (ROS), which is a sign of oxidative stress. This review concludes that the nutraceuticals (melatonin, piperine, quercetin, curcumin, resveratrol, epigallocatechin-3-gallate (EGCG), coenzyme Q10, ω-3 FA) can reduce oxidative stress and enhanced the activity of mitochondria. Furthermore, the use of nutraceuticals completely reversed the neurotoxic effects of PA on NO level and membrane potential. Additionally, the review further emphasizes the urgent need for more research into dairy-derived BCFAs and their impact on human health.

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Data Availability

The datasets supporting the findings of this study are included in the article.

Abbreviations

FAs:

Fatty acids

KBs:

Ketone bodies

BBB:

Blood-brain barrier

BCFAs:

Branched-chain fatty acids

LCFAs:

Long-chain fatty acids

PA:

Phytanic acid

ROS:

Reactive oxygen species

CNS:

Central nervous system

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Funding

The Support of DST FIST (No. SR/FST/LS-1/2017/05[C]) grant to the Department of Toxicology and DST PURSE grant (No. SR/PURSE Phase 2/39 [C]) to Jamia Hamdard is acknowledged. India Council of Medical Research (ICMR) Project grant (No.36/9/2020-TOXI-BMS) awarded to Prof. Suhel Parvez, is acknowledged. Ms. Neha received the Senior Research Fellowship from the DST-INSPIRE (File No. DST/INSPIRE/03/ 2019/001769. IVR No. 201900031405]. Dr. Shaista Chaudhary received a Senior Research Fellowship from ICMR (45/47/2013-PHA/BMS).

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  1. Department of Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, 110 062, India

    Neha, Shaista Chaudhary & Suhel Parvez

  2. Department of Physiotherapy, School of Nursing Sciences and Allied Health, Jamia Hamdard, New Delhi, 110 062, India

    Prachi Tiwari

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N., S.C., and S.P. conceptualized the review. N. and S.C. wrote the first draft. P.T. contributed to providing the mechanistic insights. S.P. finalized the final manuscript. S.P. received the necessary grants for the study.

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Correspondence to Suhel Parvez.

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Neha, Chaudhary, S., Tiwari, P. et al. Amelioration of Phytanic Acid–Induced Neurotoxicity by Nutraceuticals: Mechanistic Insights. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-03985-0

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