The effect of lycopene on the total cytochrome P450, CYP1A2 and CYP2E1

Authors

  • Melva Louisa
  • Frans D. Suyatna
  • Arini Setiawati
  • Sri W.A. Jusman

DOI:

https://doi.org/10.13181/mji.v18i4.367

Keywords:

lycopene, cytochrome P450, CYP1A2, CYP2E1

Abstract

Aim Some carotenoids such as canthaxantin, astaxanthin and beta apo-8'-carotenal were reported to have modulatory effect on the cytochrome P450. The present study was conducted to investigate the effects of lycopene, a nonprovitamin A carotenoid, on microsomal cytochrome P450, CYP1A2 and CYP2E1.

Methods Total cytochrome P450 levels, CYP1A2 and CYP2E1-catalyzed reactions (acetanilide 4-hydroxylation and p-nitrophenol hydroxylation) were studied in the liver microsomes of male Sprague Dawley rats. Microsomes were prepared using differential centrifugation combined with calcium aggregation method. Lycopene was orally administered in the dosages of 0, 25, 50 or 100 mg/kgBW/day for 14 days in a repeated fashion. Data were analyzed using ANOVA test.

Results Total cytochrome P450 level and acetanilide 4-hydroxylase activity were unaffected by any of the treatments. The CYP2E1 probe enzyme (p-nitrophenol hydroxylase) was significantly reduced by repeated administration of 100mg/ kgBW/day lycopene (7.88 + 2.04 vs 12.26 + 2.77 n mol/min/mg prot).

Conclusion The present results suggest that lycopene does not affect the total cytochrome P450 or CYP1A2 activity but it inhibits the activity of CYP2E1 (p-nitrophenol hydroxylase) in the rat. (Med J Indones 2009; 18: 233-8)

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References

Handschin C, Meyer UA. Induction of drug metabolism: the role of nuclear receptors. Pharm Rev. 2003;55:649–73.

Perroco P, Paolini M, Mazzullo M, Biagi GL and Cantelli-Forti G. v-carotene as enhancer of cell transforming activity of powerful carcinogens and cigarette-smoke condensate on BALB/c 3T3 cells in vitro. Mutat Res. 1999;440:83-90.

Gradelet S, Leclerc J, Siess MH, Astorg PO. Beta-apo-8'-carotenal, but not beta-carotene, is a strong inducer of liver cytochromes P4501A1 and 1A2 in rat. Xenobiotica. 1996;26:909-19.

Yeh SL, Hu ML. Antioxidant and pro-oxidant effects of lycopene in comparison with v-carotene on oxidant-induced damage in Hs68 cells. J Nutr Biochem. 2000;11:548–54.

The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994;330:1029–35.

Omenn GS, Goodman GE, Thornquist MD. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996;334:1150–5.

Paolini M, Antelli A, Pozzetti L, Spetlova D, Perocco P, Valgimigli L, et al. Induction of cytochrome P450 enzymes and over-generation of oxygen radicals in beta-carotene supplemented rats. Carcinogenesis. 2001;22:1483–95.

Agarwal S, Rao AV. Tomato lycopene and its role in human health and chronic disease. CMAJ. 2000;163:739–44.

Bramley PM. Is lycopene benefi cial to human health? Phytochemistry. 2000;54:233–6.

Schenkman JB, Cinti DL. Preparation of microsomes with calcium. In Methods in Enzymology. 1978;52:83–9.

Paterson BL. Methods in Enzymol. London, Academic Press 1983;91:95–7.

Omura T, Sato R. The carbon monoxide-binding pigment of liver microsomes. J Biol Chem. 1964;239:2370–85.

Swanson, MA. Glucose-6-phosphatase from liver. Methods in Enzymol. 1955;2:541–3.

Shertzer HG, Nebert DW, Senft AP, Dingeldein M, Genter MB, Dalton TP. Spectrophotometric assay for acetanilide 4-hydroxylase, an assay of CYP1A2 enzyme activity. Toxicol Methods. 2001;11:81–8

Allis JW, Robinson BL. A kinetic assay for p-Nitrophenol hydroxylase in rat liver microsomes. Anal Biochem. 1994;219:49–52.

Gonzales FJ. Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1. Mutat Res. 2005;569:101–10

Abou-Donia MB, Elmasry EM, Abu-Qare AW. Metabolism and toxicokinetics of xenobiotics. In Handbook of Toxicology. 2nd edition. Ed. MJ Derelanko, MA Hollinger. Florida: CRC Press LLC. 2002.

Hasler JA, Estabrook R, Murray M, Pikuleva I, Waterman M, Capdevila J, et al. Human cytochromes P450. Mol Aspects Med. 1999;20:1–137

Paolini M, Antelli A, Pozzetti L, Spetlova D, Perocco P, Valgimigli L, et al. Induction of cytochrome P450 enzymes and over-generation of oxygen radicals in beta-carotene supplemented rats. Carcinogenesis. 2001;22:1483–95.

Nagao A. Oxidative conversion of carotenoids to retinoids and other products. J Nutr. 2004;134:237S–40S.

Xu Y, Leo MA, Lieber CS. Lycopene attenuates alcohol apoptosis in HepG2 cells expressing CYP2E1. Biochem Biophys Res Commun. 2003;308:614–8.

Xu Y, Leo MA, Lieber CS. Lycopene attenuates alcohol arachidonic acid toxicity in HepG2 cells over expressing

CYP2E1. Biochem Biophys Res Commun. 2003;303:745–50.

Astorg P, Gradelet S, Bergès R, Suschetet M. Dietary lycopene decreases the initiation of liver preneoplastic foci by diethylnitrosamine in the rat. Nutr Cancer. 1997;29(1):60–8.

Kim DJ, Takasuka N, Kim JM, Sekine K, Ota T, Asamoto M, et al. Chemoprevention by lycopene of mouse lung neoplasia after combined initiation treatment with DEN, MNU and DMH. Cancer Lett. 1997;120: 15–22.

McCarty MF. Inhibition of CYP2E1 with natural agents may be a feasible strategy for minimizing the hepatotoxicity of ethanol. Med Hypotheses. 2001;56(1): 8–11.

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Published

2009-11-01

How to Cite

1.
Louisa M, Suyatna FD, Setiawati A, Jusman SW. The effect of lycopene on the total cytochrome P450, CYP1A2 and CYP2E1. Med J Indones [Internet]. 2009Nov.1 [cited 2024Nov.21];18(4):233-8. Available from: http://mji.ui.ac.id/journal/index.php/mji/article/view/367

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Section

Basic Medical Research
Abstract viewed = 1831 times

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