Skip to main content

Advertisement

SpringerLink
Log in

Partially saturated canthaxanthin alleviates aging-associated oxidative stress in d-galactose administered male wistar rats

  • Research Article
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

It has been earlier reported that partially saturated canthaxanthin (PSC) from Aspergillus carbonarius mutant is non-toxic, has anti-lipid peroxidation activity and can induce apoptosis in prostate cancer cell lines. In the present study, the antiaging effect of PSC was explored in d-galactose administered male wistar rats. 8–10 weeks old, male wistar rats were randomly divided into (i) Vehicle Control Group (VCG), (ii) Aged Control Group (ACG), (iii) Aged + α Lipoic Acid Group (ALG) and (iv) Aged + Partially saturated canthaxanthin Group (APG). Rats received d-galactose (300 mg /kg bwt/day; i.p.) alone (ACG) or together with PSC (APG) (20 mg/kg bwt/day; oral) and α Lipoic Acid (ALG) (80 mg/kg bwt/day; oral) for 10 weeks. Rats in VCG were injected with the same volume of physiological saline (i.p.) and fed with olive oil (vehicle). In vitro protein oxidation and DNA oxidation inhibition, in vivo malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities were determined. In addition, brain neurotransmitters, dopamine and serotonin were estimated by NMR. PSC treatment showed inhibition against protein and DNA oxidation. PSC effectively improved d-galactose induced aging rats by inducing a protective effect through up-regulation of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) and brain neurotransmitters and downregulated malondialdehyde (MDA) and monoamineoxidase (MAO) levels. Thus, PSC appears to be a functional compound having antioxidant and antiaging properties.

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
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 90(17):7915–7922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Austad SN, Fischer KE (2016) Sex differences in lifespan. Cell Metab 23:1022–1033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Babin A, Saciat C, Teixeira M, Troussard J-P, Motreuil S, Moreau J et al (2015) Limiting immunopathology: interaction between carotenoids and enzymatic antioxidant defences. Dev Comp Immunol 49(2):278–281

    Article  CAS  PubMed  Google Scholar 

  • Banji D, Banji OJ, Dasaroju S, Annamalai A (2013) Piperine and curcumin exhibit synergism in attenuating D-galactose induced senescence in rats. Eur J Pharmacol 703(1–3):91–99

    Article  CAS  PubMed  Google Scholar 

  • Blokland A (1995) Acetylcholine: a neurotransmitter for learning and memory? Brain Res Rev 21(3):285–300

    Article  CAS  PubMed  Google Scholar 

  • Bonnet U (2003) Moclobemide: therapeutic use and clinical studies. CNS Drug Rev 9(1):97–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonsall EK, Mundorff JZ, Ekvall VK, Ekvall SW (2017) 12 Nutrients, neurotransmitters, and brain dysfunction. Pediatric and adult nutrition in chronic diseases, developmental disabilities, and hereditary metabolic disorders: prevention, assessment, and treatment 103

  • Bose KSC, Agrawal B (2007) Effect of lycopene from tomatoes (cooked) on plasma antioxidant enzymes, lipid peroxidation rate and lipid profile in grade-I hypertension. Annals of Nutrition Metabolism 51(5):477–481

    Article  CAS  PubMed  Google Scholar 

  • Britz-Mckibbin P, Wong J, Chen DD (1999) Analysis of epinephrine from fifteen different dental anesthetic formulations by capillary electrophoresis. J Chromatogr A 853(1–2):535–540

    Article  CAS  PubMed  Google Scholar 

  • Castegna A, Aksenov M, Thongboonkerd V, Klein JB, Pierce WM, Booze R et al (2002) Proteomic identification of oxidatively modified proteins in Alzheimer’s disease brain. Part II: dihydropyrimidinase-related protein 2, α‐enolase and heat shock cognate 71. J Neurochem 82(6):1524–1532

    Article  CAS  PubMed  Google Scholar 

  • Chen N-Y, Liu C-W, Lin W, Ding Y, Bian Z-y, Huang L et al (2017) Extract of fructus cannabis ameliorates learning and memory impairment induced by D-galactose in an aging rats model. Evid-Based Complement Altern Med

  • Crawford A, Fassett RG, Geraghty DP, Kunde DA, Ball MJ, Robertson IK et al (2012) Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease. Gene 501(2):89–103

    Article  CAS  PubMed  Google Scholar 

  • Cui X, Zuo P, Zhang Q, Li X, Hu Y, Long J et al (2006) Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: protective effects of R‐α‐lipoic acid. J Neurosci Res 84(3):647–654

    Article  CAS  PubMed  Google Scholar 

  • Dasgupta A, Zheng J, Perrone-Bizzozero NI, Bizzozero OA (2013) Increased carbonylation, protein aggregation and apoptosis in the spinal cord of mice with experimental autoimmune encephalomyelitis

  • Davies I, O’neill PA, Mclean KA, Catania J, Bennett D (1995) Age-associated alterations in thirst and arginine vasopressin in response to a water or sodium load. Age Ageing 24(2):151–159

    Article  CAS  PubMed  Google Scholar 

  • De Iuliis A, Grigoletto J, Recchia A, Giusti P, Arslan P (2005) A proteomic approach in the study of an animal model of Parkinson’s disease. Clin Chim Acta 357(2):202–209

    Article  PubMed  CAS  Google Scholar 

  • Delgado-Vargas F, Jiménez A, Paredes-López O (2000) Natural pigments: carotenoids, anthocyanins, and betalains—characteristics, biosynthesis, processing, and stability. Crit Rev Food Sci Nutr 40(3):173–289

    Article  CAS  PubMed  Google Scholar 

  • Devaraj S, Mathur S, Basu A, Aung HH, Vasu VT, Meyers S et al (2008) A dose-response study on the effects of purified lycopene supplementation on biomarkers of oxidative stress. J Am Coll Nutr 27(2):267–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dröge W (2003) Oxidative stress and aging. In: Hypoxia. Springer, pp 191–200

  • Dubey T, Sahu G, Kumari S, Yadav BS, Sahu AN (2018) Role of herbal drugs on neurotransmitters for treating various CNS disorders: A review

  • Ellison DW, Beal MF, Martin JB (1987) Amino acid neurotransmitters in postmortem human brain analyzed by high performance liquid chromatography with electrochemical detection. J Neurosci Methods 19(4):305–315

    Article  CAS  PubMed  Google Scholar 

  • Galano A, Vargas R, Martínez A (2010) Carotenoids can act as antioxidants by oxidizing the superoxide radical anion. Phys Chem Chem Phys 12(1):193–200

    Article  CAS  PubMed  Google Scholar 

  • Geinisman Y, Detoledo-Morrell L, Morrell F, Heller RE (1995) Hippocampal markers of age-related memory dysfunction: behavioral, electrophysiological and morphological perspectives. Prog Neurobiol 45(3):223–252

    Article  CAS  PubMed  Google Scholar 

  • Ghasemzadeh A, Ghasemzadeh N (2011) Flavonoids and phenolic acids: role and biochemical activity in plants and human. J Med Plants Res 5(31):6697–6703

    CAS  Google Scholar 

  • Grimm S, Hoehn A, Davies KJ, Grune T (2011) Protein oxidative modifications in the ageing brain: consequence for the onset of neurodegenerative disease. Free Radic Res 45(1):73–88

    Article  CAS  PubMed  Google Scholar 

  • Grune T, Shringarpure R, Sitte N, Davies K (2001) Age-related changes in protein oxidation and proteolysis in mammalian cells. J Gerontol Ser A 56(11):B459–B467

    Article  CAS  Google Scholar 

  • Hadad N, Levy R (2017) Combination of EPA with carotenoids and polyphenol synergistically attenuated the transformation of microglia to M1 phenotype via inhibition of NF-κB. Neuromol Med 19(2–3):436–451

    Article  CAS  Google Scholar 

  • Halliwell B, Chirico S (1993) Lipid peroxidation: its mechanism, measurement, and significance. Am J Clin Nutr 57(5):715S–725S

    Article  CAS  PubMed  Google Scholar 

  • Hira S, Saleem U, Anwar F, Sohail MF, Raza Z, Ahmad B (2019) β-Carotene: a natural compound improves cognitive impairment and oxidative stress in a mouse model of streptozotocin-induced Alzheimer’s disease. Biomolecules 9(9):441

    Article  CAS  PubMed Central  Google Scholar 

  • Holmes E, Bonner FW, Nicholson JK (1995) Comparative studies on the nephrotoxicity of 2- bromoethanamine hydrobromide in the Fischer 344 rat and the multimammate desert mouse (Mastomys natalensis). Arch Toxicol 70:89–95

    Article  CAS  PubMed  Google Scholar 

  • Hua X, Lei M, Zhang Y, Ding J, Han Q, Hu G et al (2007) Long-term D-galactose injection combined with ovariectomy serves as a new rodent model for Alzheimer’s disease. Life Sci 80(20):1897–1905

    Article  CAS  PubMed  Google Scholar 

  • Islam M, Alam F, Solayman M, Khalil M, Kamal MA, Gan SH (2016) Dietary phytochemicals: natural swords combating inflammation and oxidation-mediated degenerative diseases. Oxid Med Cell Longev

  • Kawakami K, Kadota J-i, Iida K, Shirai R, Abe K, Kohno S (1999) Reduced immune function and malnutrition in the elderly. Tohoku J Exp Med 187(2):157–171

    Article  CAS  PubMed  Google Scholar 

  • Kingsley PB (1999) Signal intensities and T1 calculations in multiple-echo sequences with imperfect pulses. Concepts Magn Reson 11(1):29–49

    Article  CAS  Google Scholar 

  • Kızıl G, Kızıl M, Çeken B, Yavuz M, Demir H (2011) Protective ability of ethanol extracts of Hypericum scabrum L. and Hypericum retusum Aucher against the protein oxidation and DNA damage. Int J Food Prop 14(4):926–940

    Article  Google Scholar 

  • Klegeris A, Korkina LG, Greenfield SA (1995) Autoxidation of dopamine: a comparison of luminescent and spectrophotometric detection in basic solutions. Free Radic Biol Med 18(2):215–222

    Article  CAS  PubMed  Google Scholar 

  • Krinsky NI (1989) Antioxidant functions of carotenoids. Free Radic Biol Med 7(6):617–635

    Article  CAS  PubMed  Google Scholar 

  • Krinsky NI (2001) Carotenoids as antioxidants. Nutrition 17(10):815–817

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Srikanta AH, Muthukumar S, Sukumaran U-K, Govindaswamy V (2011) Antioxidant and lipid peroxidation activities in rats fed with Aspergillus carbonarius carotenoid. Food Chem Toxicol 49(12):3098–3103

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Srikanta AH, Peddha MS, Sukumaran U-K, Govindaswamy V (2012) A short-term toxicity study of Aspergillus carbonarius carotenoid. Int J Toxicol 31(2):158–165

    Article  CAS  PubMed  Google Scholar 

  • Kumaresan N, Sanjay KR, Venkatesh KS, Kadeppagari R-K, Vijayalakshmi G, Umesh-Kumar S (2008) Partially saturated canthaxanthin purified from Aspergillus carbonarius induces apoptosis in prostrate cancer cell line. Appl Microbiol Biotechnol 80(3):467–473

    Article  CAS  PubMed  Google Scholar 

  • Laemmli U (1970) SDS-page Laemmli method. Nature 227:680–685

    Article  CAS  PubMed  Google Scholar 

  • Landrum JT (2013) Reactive oxygen and nitrogen species in biological systems: reactions and regulation by carotenoids. In: Carotenoids and human health. Springer, pp 57–101

  • Levine RL, Stadtman ER (2001) Oxidative modification of proteins during aging. Exp Gerontol 36(9):1495–1502

    Article  CAS  PubMed  Google Scholar 

  • Lin J, Huang L, Yu J, Xiang S, Wang J, Zhang J et al (2016) Fucoxanthin, a marine carotenoid, reverses scopolamine-induced cognitive impairments in mice and inhibits acetylcholinesterase in vitro. Mar Drugs 14(4):67

    Article  PubMed Central  CAS  Google Scholar 

  • Lin H-C, Lin M-H, Liao J-H, Wu T-H, Lee T-H, Mi F-L et al (2017) Antroquinonol, a ubiquinone derivative from the mushroom Antrodia camphorata, inhibits colon cancer stem cell-like properties: insights into the molecular mechanism and inhibitory targets. J Agric Food Chem 65(1):51–59

    Article  CAS  PubMed  Google Scholar 

  • Long J, Wang X, Gao H, Liu Z, Liu C, Miao M et al (2007) D-galactose toxicity in mice is associated with mitochondrial dysfunction: protecting effects of mitochondrial nutrient R-alpha-lipoic acid. Biogerontology 8(3):373–381

    Article  CAS  PubMed  Google Scholar 

  • Meraz Rios MA, Toral-Rios D, Franco-Bocanegra D, Villeda-Hernández J, Campos-Peña V (2013) Inflammatory process in Alzheimer’s disease. Front Integr Nuerosci 7:59

    Article  Google Scholar 

  • Milatovic D, Gupta RC, Aschner M (2006) Anticholinesterase toxicity and oxidative stress. Sci World J 6:295–310

    Article  CAS  Google Scholar 

  • Min J-y, Min K-b (2014) Serum lycopene, lutein and zeaxanthin, and the risk of Alzheimer’s disease mortality in older adults. Dement Geriatr Cogn Disord 37(3–4):246–256

    Article  CAS  PubMed  Google Scholar 

  • Moini M, Schultz CL, Mahmood H (2003) CE/electrospray ionization-MS analysis of underivatized d/l-amino acids and several small neurotransmitters at attomole levels through the use of 18-crown-6-tetracarboxylic acid as a complexation reagent/background electrolyte. Anal Chem 75(22):6282–6287

    Article  CAS  PubMed  Google Scholar 

  • Molz P, Schröder N (2017) Potential therapeutic effects of lipoic acid on memory deficits related to aging and neurodegeneration. Front Pharmacol 8:849

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Niranjan R (2014) The role of inflammatory and oxidative stress mechanisms in the pathogenesis of Parkinson’s disease: focus on astrocytes. Mol Neurobiol 49(1):28–38

    Article  CAS  PubMed  Google Scholar 

  • Olanow C (1993) A radical hypothesis for neurodegeneration. Trends Neurosci 16(11):439–444

    Article  CAS  PubMed  Google Scholar 

  • Oliver CN, Ahn B-W, Moerman EJ, Goldstein S, Stadtman ER (1987) Age-related changes in oxidized proteins. J Biol Chem 262(12):5488–5491

    Article  CAS  PubMed  Google Scholar 

  • Paradies G, Petrosillo G, Paradies V, Ruggiero FM (2011) Mitochondrial dysfunction in brain aging: role of oxidative stress and cardiolipin. Neurochem Int 58(4):447–457

    Article  CAS  PubMed  Google Scholar 

  • Parrot S, Neuzeret P-C, Denoroy L (2011) A rapid and sensitive method for the analysis of brain monoamine neurotransmitters using ultra-fast liquid chromatography coupled to electrochemical detection. J Chromatogr B 879(32):3871–3878

    Article  CAS  Google Scholar 

  • Pow DV, Wright LL, Vaney DI (1995) The immunocytochemical detection of amino-acid neurotransmitters in paraformaldehyde-fixed tissues. J Neurosci Methods 56(2):115–123

    Article  CAS  PubMed  Google Scholar 

  • Qingming Y, Xianhui P, Weibao K, Hong Y, Yidan S, Li Z et al (2010) Antioxidant activities of malt extract from barley (Hordeum vulgare L.) toward various oxidative stress in vitro and in vivo. Food Chem 118(1):84–89

    Article  CAS  Google Scholar 

  • Quantitative NMR Spectroscopy.dox 11/2017, University of Oxford

  • Sánchez-Moreno C, Plaza L, de Ancos B, Cano MP (2006) Nutritional characterisation of commercial traditional pasteurised tomato juices: carotenoids, vitamin C and radical-scavenging capacity. Food Chem 98(4):749–756

    Article  CAS  Google Scholar 

  • Sarubbo F, Ramis M, Aparicio S, Ruiz L, Esteban S, Miralles A et al (2015) Improving effect of chronic resveratrol treatment on central monoamine synthesis and cognition in aged rats. Age 37(3):37

    Article  PubMed Central  CAS  Google Scholar 

  • Shemyakov S (2001) Monoamine oxidase activity, lipid peroxidation, and morphological changes in human hypothalamus during aging. Bull Exp Biol Med 131(6):586–588

    Article  CAS  PubMed  Google Scholar 

  • Sies H (2000) What is oxidative stress? In: Oxidative stress and vascular disease. Springer, pp 1–8

  • Wang J, Li L, Wang Z, Cui Y, Tan X, Yuan T et al (2018) Supplementation of lycopene attenuates lipopolysaccharide-induced amyloidogenesis and cognitive impairments via mediating neuroinflammation and oxidative stress. J Nutr Biochem 56:16–25

    Article  CAS  PubMed  Google Scholar 

  • Wu W, Wang X, Xiang Q, Meng X, Peng Y, Du N et al (2014) Astaxanthin alleviates brain aging in rats by attenuating oxidative stress and increasing BDNF levels. Food function 5(1):158–166

    Article  CAS  PubMed  Google Scholar 

  • Xavier AAO, Pérez-Gálvez A (2016) Carotenoids as a source of antioxidants in the diet. In: Carotenoids in nature. Springer, pp 359–375

  • Xian Y-F, Lin Z-X, Zhao M, Mao Q-Q, Ip S-P, Che C-T (2011) Uncaria rhynchophylla ameliorates cognitive deficits induced by D-galactose in mice. Planta Med 77(18):1977–1983

    Article  CAS  PubMed  Google Scholar 

  • Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C (2003) Interaction between flavonoids and the blood–brain barrier: in vitro studies. J Neurochem 85(1):180–192

    Article  CAS  PubMed  Google Scholar 

  • Youdim KA, Shukitt-Hale B, Joseph JA (2004) Flavonoids and the brain: interactions at the blood–brain barrier and their physiological effects on the central nervous system. Free Radic Biol Med 37(11):1683–1693

    Article  CAS  PubMed  Google Scholar 

  • Yu Y, Bai F, Wang W, Liu Y, Yuan Q, Qu S et al (2015) Fibroblast growth factor 21 protects mouse brain against D-galactose induced aging via suppression of oxidative stress response and advanced glycation end products formation. Pharmacol Biochem Behav 133:122–131

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Pi Z, Song F, Liu Z (2016) Ginsenosides attenuate D-galactose-and AlCl3-inducedspatial memory impairment by restoring the dysfunction of the neurotransmitter systems in the rat model of Alzheimer’s disease. J Ethnopharmacol 194:188–195

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Grants from the Department of Science and Technology (DST), Science and Engineering Research Board (SERB), New Delhi, India under Young Scientist Scheme (Project No. YSS/2015/000298). The authors gratefully acknowledge SAIF, CSIR-CDRI for providing analytical facilities and Laboratory Animal Facility (LAF), CSIR-CDRI for support with animal experimentation. Authors also thankful to Mr. C. S. Yadav and Mr. Dinesh Kumar of LAF, CSIR-CDRI and Anurag Srivastava, Toxicology Division for providing technical support. The manuscript bears CSIR-CDRI communication number 10115.

Author information

Authors and Affiliations

  1. Department of Biotechnology, Periyar Maniammai Institute of Science & Technology, Vallam, Thanjavur, Tamil Nadu, India

    Ahila Mathimaran & Anbarasu Kumar

  2. Sophisticated Analytical Instrument Facility, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow, Uttar Pradesh, India

    Gurudayal Prajapati & Ravi S. Ampapathi

  3. Laboratory Animal Facility, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow, Uttar Pradesh, India

    Ahila Mathimaran, Himangsu K. Bora & Rajdeep Guha

  4. CSIR-Academy of Scientific and Innovative Research (CSIR-AcSIR), Ghaziabad, Uttar Pradesh, India

    Ravi S. Ampapathi & Rajdeep Guha

Authors
  1. Ahila Mathimaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anbarasu Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gurudayal Prajapati
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ravi S. Ampapathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Himangsu K. Bora
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rajdeep Guha
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AM and GP performed the experiments, analysed the data. AM, AK and RG designed the study, analysed the data and drafted the manuscript. RSA designed the NMR experiments, analysed the data and contributed to the manuscript. HKB analysed and interpreted the histopathological data and contributed to the manuscript. All the authors read and approved the manuscript.

Corresponding authors

Correspondence to Anbarasu Kumar or Rajdeep Guha.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

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

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mathimaran, A., Kumar, A., Prajapati, G. et al. Partially saturated canthaxanthin alleviates aging-associated oxidative stress in d-galactose administered male wistar rats. Biogerontology 22, 19–34 (2021). https://doi.org/10.1007/s10522-020-09898-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-020-09898-4

Keywords

Search

Navigation