Skip to main content
SpringerLink
Log in

Linoleic Acid Supplementation Attenuates Inflammation and Redox Imbalance During Aging in Wistar Rats

  • ORIGINAL RESEARCH ARTICLE
  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

Aging is the result of the accumulation of a variety of cellular and molecular damage over time. The oxidative stress-induced functional impairments are known to be the cause of age-related deficits. This study aimed to evaluate the effect of Linoleic acid (LA) supplementation on biomarkers of oxidative stress and inflammation in blood of young and old rats. Male rats in young and old groups were divided randomly into four distinct groups (n = 6). Group I: Young Control, Group II: Young Treated, Group III: Old Control, Group IV: Old Treated. Group II and IV were administered with LA (5 mg/kg body weight) orally via gavage for 28 days. After completion of the experimental protocol, rats were sacrificed and parameters of oxidative stress and inflammation were determined. Results show a significant (p ≤ 0.05) decrease in the level of Ferric reducing antioxidant potential (FRAP), Superoxide dismutase (SOD), Catalase (CAT), Reduced glutathione (GSH) in plasma and Plasma membrane redox system (PMRS) in RBCs and there was up-regulation in the levels of Intracellular ROS, Malondialdehyde (MDA), Advanced oxidation protein products (AOPPs), Protein carbonyl oxidation (PCO), Inflammatory cytokines: CRP, IL-6, TNF-α, COX and LOX in old rats when compared to young rats. After treatment with LA significant (p ≤ 0.05) increase in the level of FRAP, PMRS, GSH, SOD and CAT was reported and a significant decrease in the level of ROS, MDA, PCO, AOPP and inflammatory cytokines. The findings substantiate the putative role of LA in maintaining redox homeostasis in blood and preventing increase in inflammatory markers in blood.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

Supplementary material associated with this article can be found, at doi: https://doi.org/10.17632/mvcjhfxkzv.1.

References

  1. Harman D. The free radical theory of aging. Antioxid Redox Signal. 2003;5:557–61.

    Article  CAS  PubMed  Google Scholar 

  2. Saraswat K, Rizvi SI. Novel strategies for anti-aging drug discovery. Expert Opin Drug Discov. 2017;12:955–66.

    Article  CAS  PubMed  Google Scholar 

  3. Maldonado E, Morales-Pison S, Urbina F, Solari A. Aging hallmarks and the role of oxidative stress. Antioxidants. 2023;12:651.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kaur N, Chugh V, Gupta AK. Essential fatty acids as functional components of foods—a review. J Food Sci Technol. 2014;51:2289–303.

    Article  CAS  PubMed  Google Scholar 

  5. Sokoła-Wysoczańska E, Wysoczański T, Wagner J, Czyż K, Bodkowski R, Lochyński S, et al. Polyunsaturated fatty acids and their potential therapeutic role in cardiovascular system disorders—a review. Nutrients. 2018;10:1561.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Stavrinou PS, Andreou E, Aphamis G, Pantzaris M, Ioannou M, Patrikios IS, Giannaki C. The effects of a 6-month high dose omega-3 and omega-6 polyunsaturated fatty acids and antioxidant vitamins supplementation on cognitive function and functional capacity in older adults with mild cognitive impairment. Nutrients. 2020;12(2):325.

    Article  CAS  PubMed  Google Scholar 

  7. Harris WS, Pottala JV, Varvel SA, Borowski JJ, Ward JN, McConnell JP. Erythrocyte omega-3 fatty acids increase and linoleic acid decreases with age: Observations from 160,000 patients. Prostaglandins Leukot Essent Fatty Acids. 2013;88:257–63.

    Article  CAS  PubMed  Google Scholar 

  8. de Groot RHM, van Boxtel MPJ, Schiepers OJG, Hornstra G, Jolles J. Age dependence of plasma phospholipid fatty acid levels: potential role of linoleic acid in the age-associated increase in docosahexaenoic acid and eicosapentaenoic acid concentrations. Br J Nutr. 2009;102:1058–64.

    Article  PubMed  Google Scholar 

  9. Chung HY, Lee EK, Choi YJ, Kim JM, Kim DH, Zou Y, et al. Molecular inflammation as an underlying mechanism of the aging process and age-related diseases. J Dent Res. 2011;90(7):830–40.

    Article  CAS  PubMed  Google Scholar 

  10. Chung HY, Kim DH, Lee EK, Chung KW, Chung S, Lee B, et al. Redefining chronic inflammation in aging and age-related diseases: proposal of the senoinflammation concept. Aging Dis. 2019;10:367–82.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Franceschi C, Garagnani P, Morsiani C, Conte M, Santoro A, Grignolio A, et al. The continuum of aging and age-related diseases: common mechanisms but different rates. Front Med. 2018. https://doi.org/10.3389/fmed.2018.00061.

    Article  Google Scholar 

  12. Yang B, Zhou Y, Wu M, Li X, Mai K, Ai Q. ω-6 Polyunsaturated fatty acids (linoleic acid) activate both autophagy and antioxidation in a synergistic feedback loop via TOR-dependent and TOR-independent signaling pathways. Cell Death Dis. 2020;11:607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Atayik MC, Çakatay U. Age-adjustment expertise in rat models of human diseases. In: Rizvi SI, editor. Emerging anti-aging strategies. Singapore: Springer; 2023. p. 331–40.

    Chapter  Google Scholar 

  14. Cooper RL, Linnoila M. Sexual behavior in aged, noncycling female rats. Physiol Behav. 1977;18:573–6.

    Article  CAS  PubMed  Google Scholar 

  15. Azemi NA, Azemi AK, Abu-Bakar L, Sevakumaran V, Muhammad TST, Ismail N. Effect of linoleic acid on cholesterol levels in a high-fat diet-induced hypercholesterolemia rat model. Metabolites. 2022;13:53.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Singh AK, Singh S, Garg G, Rizvi SI. Rapamycin alleviates oxidative stress-induced damage in rat erythrocytes. Biochem Cell Biol. 2016;94:471–9.

    Article  CAS  PubMed  Google Scholar 

  17. Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972;247:3170–5.

    Article  CAS  PubMed  Google Scholar 

  18. Aebi H, Wyss SR, Scherz B, Skvaril F. Heterogeneity of erythrocyte catalase II. Isolation and characterization of normal and variant erythrocyte catalase and their subunits. Eur J Biochem. 1974;48:137–45.

    Article  CAS  PubMed  Google Scholar 

  19. Arya JK, Kumar R, Singh A, Srivastava P, Yadawa AK, Rizvi SI. Acarbose, an α-glucosidase inhibitor, maintains altered redox homeostasis during aging by targeting glucose metabolism in rat erythrocytes. Rejuvenation Res. 2023;26:21–31.

    Article  CAS  PubMed  Google Scholar 

  20. Singh S, Garg G, Singh AK, Bissoyi A, Rizvi SI. Fisetin, a potential caloric restriction mimetic, attenuates senescence biomarkers in rat erythrocytes. Biochem Cell Biol. 2019;97:480–7.

    Article  CAS  PubMed  Google Scholar 

  21. Garg G, Singh S, Singh AK, Rizvi SI. Metformin alleviates altered erythrocyte redox status during aging in rats. Rejuvenation Res. 2017;20:15–24.

    Article  CAS  PubMed  Google Scholar 

  22. Kumar R, Akhtar F, Rizvi SI. Hesperidin attenuates altered redox homeostasis in an experimental hyperlipidaemic model of rat. Clin Exp Pharmacol Physiol. 2020;47:571–82.

    Article  CAS  PubMed  Google Scholar 

  23. Esterbauer H, Cheeseman KH. [42] Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. In: Packer L, Glazer AN, editors. Methods in enzymology. Amsterdam: Elsevier; 1990. p. 407–21.

    Google Scholar 

  24. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 1990;186:464–78.

    Article  CAS  PubMed  Google Scholar 

  25. Verma AK, Singh S, Rizvi SI. Redox homeostasis in a rodent model of circadian disruption: Effect of melatonin supplementation. Gen Comp Endocrinol. 2019;280:97–103.

    Article  CAS  PubMed  Google Scholar 

  26. Leyane TS, Jere SW, Houreld NN. Oxidative stress in ageing and chronic degenerative pathologies: molecular mechanisms involved in counteracting oxidative stress and chronic inflammation. IJMS. 2022;23:7273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014;2014: 360438.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lin L, Jiao M, Zhao M, Sun W. In vitro gastrointestinal digest of catechin-modified β-conglycinin oxidized by lipoxygenase-catalyzed linoleic acid peroxidation. Food Chem. 2019;280:154–63.

    Article  CAS  PubMed  Google Scholar 

  29. Reynés B, Palou M, Palou A. Gene expression modulation of lipid and central energetic metabolism related genes by high-fat diet intake in the main homeostatic tissues. Food Funct. 2017;8:629–50.

    Article  PubMed  Google Scholar 

  30. So N, Jr B, T W, Ei I. Characterization and nutritional evaluation of detarium senegalense seed oil -based diet in male wistar rats. NFSIJ. 2018;7:1–9.

  31. Yang H-L, Korivi M, Lin M-K, Chang HC-W, Wu C-R, Lee M-S, et al. Antihemolytic and antioxidant properties of pearl powder against 2,2′-azobis(2-amidinopropane) dihydrochloride-induced hemolysis and oxidative damage to erythrocyte membrane lipids and proteins. J Food Drug Anal. 2017;25:898–907.

    Article  CAS  PubMed  Google Scholar 

  32. Wang R, Kern JT, Goodfriend TL, Ball DL, Luesch H. Activation of the antioxidant response element by specific oxidized metabolites of linoleic acid. Prostaglandins Leukot Essent Fatty Acids. 2009;81:53–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ahmad S, Beg ZH. Evaluation of therapeutic effect of omega-6 linoleic acid and thymoquinone enriched extracts from Nigella sativa oil in the mitigation of lipidemic oxidative stress in rats. Nutrition. 2016;32:649–55.

    Article  CAS  PubMed  Google Scholar 

  34. Rizvi SI, Jha R, Maurya PK. Erythrocyte plasma membrane redox system in human aging. Rejuvenation Res. 2006;9:470–4.

    Article  CAS  PubMed  Google Scholar 

  35. Rodríguez-Aguilera JC, López-Lluch G, Santos-Ocaña C, Villalba JM, Gómez-Díaz C, Navas P. Plasma membrane redox system protects cells against oxidative stress. Redox Rep. 2000;5:148–50.

    Article  PubMed  Google Scholar 

  36. Kawamoto Y, Nakamura Y, Naito Y, Torii Y, Kumagai T, Osawa T, et al. Cyclopentenone prostaglandins as potential inducers of phase II detoxification enzymes. 15-deoxy-delta(12,14)-prostaglandin j2-induced expression of glutathione S-transferases. J Biol Chem. 2000;275:11291–9.

    Article  CAS  PubMed  Google Scholar 

  37. Liu Y, Kern JT, Walker JR, Johnson JA, Schultz PG, Luesch H. A genomic screen for activators of the antioxidant response element. Proc Natl Acad Sci USA. 2007;104:5205–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kehm R, Baldensperger T, Raupbach J, Höhn A. Protein oxidation—formation mechanisms, detection and relevance as biomarkers in human diseases. Redox Biol. 2021;42: 101901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Feldman JL, Baeza J, Denu JM. Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins. J Biol Chem. 2013;288:31350–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Raj P, Singh M, Rawat JK, Gautam S, Saraf SA, Kaithwas G. Effect of enteral administration of α-linolenic acid and linoleic acid against methotrexate induced intestinal toxicity in albino rats. RSC Adv. 2014;4:60397–403.

    Article  CAS  Google Scholar 

  41. Lu N, Du Y, Li H, Luo Y, Ouyang B, Chen Y, et al. Omega-6 fatty acids down-regulate matrix metalloproteinase expression in a coronary heart disease-induced rat model. Int J Exp Path. 2018;99:210–7.

    Article  CAS  Google Scholar 

  42. Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018;15:505–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Araujo P, Belghit I, Aarsæther N, Espe M, Lucena E, Holen E. The effect of omega-3 and omega-6 polyunsaturated fatty acids on the production of cyclooxygenase and lipoxygenase metabolites by human umbilical vein endothelial cells. Nutrients. 2019;11:966.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Das UN. Bioactive lipids in age-related disorders. In: Guest PC, editor. Reviews on new drug targets in age-related disorders. Cham: Springer; 2020. p. 33–83. https://doi.org/10.1007/978-3-030-42667-5_3.

    Chapter  Google Scholar 

  45. Das UN. “Cell membrane theory of senescence” and the role of bioactive lipids in aging, and aging associated diseases and their therapeutic implications. Biomolecules. 2021;11:241.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Authors gratefully acknowledge for the funding and facilities received by Department of Biochemistry, University of Allahabad, India.

Funding

The research is funded by UGC-SAP grant of Department of Biochemistry, University of Allahabad, India.

Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Allahabad, Allahabad, Uttar Pradesh, 211002, India

    Parisha Srivastava, Avnish Kumar Verma, Akanksha Singh, Raushan Kumar & Syed Ibrahim Rizvi

Authors
  1. Parisha Srivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Avnish Kumar Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akanksha Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Raushan Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Syed Ibrahim Rizvi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PS and SIR conceived and designed the experiments. PS, AS and RK performed the experiments. AKV and SIR analyzed the data. PS and SIR wrote the paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Syed Ibrahim Rizvi.

Ethics declarations

Conflict of interest

Authors have no competing interests to be declared.

Ethical Approval

All animal care and exploratory methods conformed to the guidelines of the Control and Supervision of Experiments on Animals (CPCSEA) and Institutional Animal Ethics Committee (IAEC), University of Allahabad, India and also follow guidelines for the Care and Use of Laboratory Animals (1996, published by National Academy Press, 2101 Constitution Ave. NW, Washington, DC 20055, USA).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Srivastava, P., Verma, A.K., Singh, A. et al. Linoleic Acid Supplementation Attenuates Inflammation and Redox Imbalance During Aging in Wistar Rats. Ind J Clin Biochem (2024). https://doi.org/10.1007/s12291-024-01233-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12291-024-01233-9

Keywords

Search

Navigation