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Protective Effect of Resveratrol against Oxidation Stress Induced by 2-Nitropropane in Rat Liver

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DOI: 10.4236/pp.2011.23017    4,798 Downloads   10,038 Views   Citations

ABSTRACT

We investigated the effect of resveratrol on oxidation damage and variation of antioxidant defences induced by 2-nitropropane (2-NP) in rat liver. One group of five rats was given resveratrol (50 mg/kg/d body weight) in the diet until the end of the experiment. After 14 days, 2-NP (100 mg/kg) was injected i.p. into two groups of animals (2-NP + Res and 2-NP groups) while control animals were treated with vehicle alone. Animals were killed by decapitation 15 h after 2-NP injection. The levels of 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodGuo) were significantly increased by 2-NP injection, but resveratrol restored 8-oxodGuo to levels similar to those measured in controls. Superoxide dismutase (SOD) and xanthine oxidase (XO) activities in the liver were significantly increased by 2-NP, but were similar to those found in the group treated with resveratrol and 2-NP (2-NP + Res). We also observed that 2-NP injection significantly reduced GSH/GSSG ratio in the liver and this change was partially reversed by resveratrol treatment. Moreover, an increased (p = 0.06) expression of the oxoguanine glycosylase (OGG1) gene was found in 2-NP rats, whereas pre-treatment with resveratrol restored OGG1 expression to control levels. An up-regulation of caspase-3 was also observed in 2-NP group, but resveratrol significantly reduced the activation of caspase-3. An inverse correlation was found between GSH/GSSG and 8-oxodGuo in the 2-NP group. On the contrary, 8-oxodGuo levels, GSH/GSSG ratio, XO and SOD activities in the colon mucosa of 2-NP rats were similar to those of controls confirming that the colon is not a target of oxidation damage 2-NP induced. In conclusion, our results indicate that oxidative DNA damage and apoptosis are the main mechanisms of cell death in a model of chemically induced severe acute hepatic injury and in this early stage of damage pharmacological doses of resveratrol can ameliorate hepatic oxidation damage by its antioxidant and scavenging properties through a reduction of XO activity, a partial restoration of GSH/GSSG ratio in addition to its capacity to inhibit apoptosis.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

M. Lodovici, E. Bigagli, C. Luceri, E. Manni and M. Zaid, "Protective Effect of Resveratrol against Oxidation Stress Induced by 2-Nitropropane in Rat Liver," Pharmacology & Pharmacy, Vol. 2 No. 3, 2011, pp. 127-135. doi: 10.4236/pp.2011.23017.

References

[1] H. Wei, “Activation of oncogenes and/or inactivation of anti-oncogenes by reactive oxygen species,” Medical Hypotheses Vol. 39, No. 3, 1992, pp. 267-267.
[2] T. Takeuchi and K. Morimoto, “Increased formation of 8-hydroxydeoxyguanosine, an oxidative DNA damage, in lymphoblasts from Fanconi's anemia patients due to possible catalase deficiency,” Carcinogenesis Vol. 14, No. 6, 1993, pp. 1115-1120.
[3] R. Shimoda, M. Nagashima, M. Sakamoto, N. Yamaguchi, S. Hirohashi, J. Yokota, H. Kasai, “Increased formation of oxidative DNA damage, 8-hydroxydeoxyguanosine, in human livers with chronic hepatitis,” Cancer Research Vol. 54, No. 12, 1994, pp. 3171-3172.
[4] M.B. Reddy and L. Clark “Iron, oxidative stress, and disease risk,” Nutrition Reviews Vol. 62, No. 3, 2004, pp. 120-124.
[5] [5] A. M. Shah, and K. M. Channon, “Free radicals and redox signalling in cardiovascular disease,” Heart Vol. 90, No. 5, 2004, pp. 486-487.
[6] Y. J. Cai, J.G. Fang, L.P. Ma, L. Yang, Z.L. Liu, “Inhibition of free radical-induced peroxidation of rat liver microsomes by resveratrol and its analogues,” Biochimica et Biophisica Acta Vol. 1637, No. 1, 2003, pp. 31-38.
[7] A. Cavallaro, T. Ainis, C. Bottari, V. Fimiani, “Effect of resveratrol on some activities of isolated and in whole blood human neutrophils,” Physiological Research Vol. 52, No. 5, 2003, pp. 555-562.
[8] G.C.Yen, P.D. Duh, C.W. Lin, “Effects of resveratrol and 4-hexylresorcinol on hydrogen peroxide-induced oxidative DNA damage in human lymphocytes,” Free Radical Research Vol. 37, No. 5, 2003, pp. 509-514.
[9] H. Sha, Q. Ma, R.K. Jha, F. Xu, L. Wang, Z. Wang, Y. Zhao, F. Fan “Resveratrol ameliorates hepatic injury via the mitochondrial pathway in rats with severe acute pancreatitis,” European Journal of Pharmacology Vol. 601, No. 1-3, 2008, pp. 136-142.
[10] D. Delmas, A. Lan?on, D. Colin, B. Jannin, N. Latruffe, “Resveratrol as a chemopreventive agent: a promising molecule for fighting cancer”, Current Drug Targets Vol. 7, No. 4, 2006, pp. 423-442.
[11] E. Tili, J.J. Michaille, H. Alder, S. Volinia, D. Delmas, N. Latruffe, C.M. Croce, “Resveratrol modulates the levels of microRNAs targeting genes encoding tumor-suppressors and effectors of TGFβ signaling pathway in SW480 cells,” HBiochemical PharmacolHogy Vol. 80, No. 12, 2010, pp. 2057-2065.
[12] S. Pervaiz, “ Chemotherapeutic potential of the chemopreventive phytoalexin resveratrol” Drug Resistance Updates Vol. 7, No. 6, 2004, pp. 333-344.
[13] K.B. Harikumar, B.B. Aggarwal, “Resveratrol: a multi targeted agent or age-associated chronic diseases” Cell Cycle Vol. 7, No. 8, 2008, pp. 1020-1035.
[14] M.A. HSiddiquiH, M.P. HKashyapH, V. HKumarH, A.A. HAl-Khedhairy,H J. HMusarratH, A.B. HPantH, “Protective potential of trans-resveratrol against 4-hydroxynonenal induced damage in PC12 cells” HToxicology In VitroH Vol. 24, N. 6, 2010, pp. 1592-1598.
[15] T. HTunali-AkbayH, O. HSehirliH, F. HErcanH, G. HSenerH “Resveratrol protects against methotrexate-induced hepatic injury in rats” HJournal of Pharmacology and Pharmacy ScienceH Vol. 13, No. 2, 2010, pp. 303-310.
[16] A. HBishayee, K.F.H HBarnesH, D. HBhatiaH, A.S. HDarveshH, R.T. HCarrollH, “Resveratrol suppresses oxidative stress and inflammatory response in diethylnitrosamine-initiated rat hepatocarcinogenesis” HCancer Prevention and ResearchH Vol. 3, No. 6, 2010, pp. 753-763.
[17] R. Harrison, G. Letz, G. Pasternak, P. Blanc, “Fulminant hepatic failure after occupational exposure to 2-nitropropane,” Annals of Internal Medicine Vol. 107, No. 4, 1987, pp. 466-468.
[18] E.S. Fiala, C.C. Conaway, G.E. Mathis, “Oxidative DNA and RNA damage in the livers of Sprague–Dawley rats treated with the hepatocarcinogen 2-nitropropane” Cancer Research Vol. 49, No. 20, 1989, pp. 5518-5522.
[19] R.S. Sodum, G. Nie, E.S. Fiala, “H8-Aminoguanine: a base modification produced in rat liver nucleic acids by the hepatocarcinogen 2-nitropropaneH” Chemical Research of Toxicology Vol.6, No. 3, 1993, pp. 269-276.
[20] C. Casalini, M. Lodovici, C. Briani, G. Paganelli, S. Remy, V. Cheynier, P. Dolara, “HEffect of complex polyphenols and tannins from red wine (WCPT) on chemically induced oxidative DNA damage in the rat,”H European Journal of Nutrition Vol. 38, No. 4, 1999, pp. 190-195.
[21] [21] L.P. Borges, C.W. Nogueira, R.P. Panatieri, J.B.T Rocha, G. Zeni “Acute liver damage induced by 2-nitropropane in rats: Effect of diphenyl diselenide on antioxidant defences” Chemico- Biological Interactions Vol. 160, No. 2, 2006, pp. 99-107.
[22] A. HUnnikrishnan,H J.J. HRaffoulH, H.V. HPateH, T.M. HPrychitkoH, N. HAnyangweH, L.B. HMeira,H E.C. HFriedbergH, D.C. HCabelofH, A.R. HHeydari,H “Oxidative stress alters base excision repair pathway and increases apoptotic response in apurinic/apyrimidinic endonuclease 1/redox factor-1 haploinsufficient mice” HFree Radical Biology and MedHicine Vol. 46, No. 11, 2009, pp. 1488-1499.
[23] L.D.Williams, G.A. Burdock, J.A. Edwards, M. Beck, J. Bausch, L.D. Williams, G.A. Burdock, J.A. Edwards, M. Beck, J. Bausch, “Safety studies conducted on high-purity trans-resveratrol in experimental animals” HFood and Chemical ToxicolHogy Vol. 47, No. 9, 2009, pp. 2170-2182.
[24] A. Bishayee, “Cancer prevention and treatment with resveratrol: from rodent studies to clinical trials,” Cancer Prevention Research Vol. 2, No. 5, 2009, pp. 409-418
[25] C. M. Gedik, A. Collins, ESCODD (European Standards Committee on Oxidative DNA Damage) “Establishing the background level of base oxidation in human lymphocyte DNA: results of an interlaboratory validation study” HFASEB JHournal Vol. 19, No. 1, 2005, pp. 82-84.
[26] M. HLodoviciH, C. HCasaliniH, R. HCariaggiH, L. HMichelucciH, P. HDolaraH, “Levels of 8-hydroxydeoxyguanosine as a marker of DNA damage in human leukocytes” HFree Radical Biology and MedHicine Vol. 28, No. 1, 2000, pp. 13-17.
[27] V. HCorrea-SaldeH, I. HAlbesaH, “Reactive oxidant species and oxidation of protein and haemoglobin as biomarkers of susceptibility to stress caused by chloramphenicol” HBiomedical PharmacotherHapy Vol. 63, No. 2, 2009, pp. 100-104.
[28] R. HMateosH, E. HLecumberriH, S. HRamosH, L. HGoyaH, L. HBravoH, “ Determination of malondialdehyde (MDA) by high-performance liquid chromatography in serum and liver as a biomarker for oxidative stress. Application to a rat model for hypercholesterolemia and evaluation of the effect of diets rich in phenolic antioxidants from fruits “HJournal of Chromatography B-Analytical Technologies in the Biomedical and Life SciHence Vol. 827, No. 1, 2005, pp. 76-82.
[29] C. Beauchamp, I. Fridovich, “Superoxide dismutase: improved assays and an assay applicable to acrylamide gels” HAnalytical BiochemHistry Vol. 44, No. 1, 1971, pp. 276-287.
[30] E. D. Corte, F. Stirpe, “Regulation of xanthine oxidase in rat liver: modifications of the enzyme activity of rat liver supernatant on storage at 20 degrees” Biochemical Journal Vol. 108, No. 2, 1968, pp. 349-351.
[31] C. Cereser, J. Guichard, J. Drai, E. Bannier, I. Garcia, S. Boget, P. Parvaz, A. Revol, “Quantitation of reduced and total glutathione at the femtomole level by high-performance liquid chromatography with fluorescence detection: application to red blood cells and cultured fibroblasts” Journal of Chromatography BH Biomedical Sciences and ApplHications Vol. 752, No. 1, 2001, pp. 123-132.
[32] C. Luceri, G. Caderni, A. Sanna, P. Dolara, “HRed wine and black tea polyphenols modulate the expression of cycloxygenase-2, inducible nitric oxide synthase and glutathione-related enzymes in azoxymethane-induced f344 rat colon tumors”H Journal of Nutrition Vol. 132, No. 6, 2002, pp. 1376-1379.
[33] X. S. HDengH, J. HTuoH, H.E. HPoulsenH, S. HLoftH, “Prevention of oxidative DNA damage in rats by brussels sprouts” HFree Radical ResHearch Vol. 28, No. 3, 1998, pp. 323-333.
[34] G. HBarja, “H Resveratrol, melatonin, vitamin E, and PBN protect against renal oxidative DNA damage induced by the kidney carcinogen KBrO3” HFree Radical Biology and MedHicine Vol. 26, No. 11-12, 1999, pp. 1531-1534.
[35] K.H Mizutani, K. Ikeda, Y. Kawai, Y. Yamori,” Protective effect of resveratrol on oxidative damage in male and female stroke-prone spontaneously hypertensive rats”H Clinical and Experimental Pharmacology and Physiology Vol. 28, No. 1-2, 2001, pp. 55-59.
[36] B. Halliwell, J.M. Gutteridge, “HRole of free radicals and catalytic metal ions in human disease: an overview”H Methods in Enzymology Vol. 186, 1990, pp. 1-85.
[37] W. HBorsH, C. HMichelH, C. HDalkeH, K. HStettmaierH, M. HSaranH, U. HAndraeH, “Radical intermediates during the oxidation of nitropropanes. The formation of NO2 from 2-nitropropane, its reactivity with nucleosides, and implications for the genotoxicity of 2-nitropropane” HChemical Research in ToxicolHogy Vol. 6, No. 3, 1993, pp. 302-309.
[38] [38] C. HKohlH, P. HMorganH, A. HGescherH, “Metabolism of the genotoxicant 2-nitropropane to a nitric oxide species” HChemico-Biological InteractHions Vol. 97, No. 2, 1995, pp. 185-194.
[39] S.S. Leonard, C. Xia, B.H. Jiang, B. Stinefelt, H. Klandorf, G.K. Harris, X. Shi, " Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses” Biochemical and Biophysical Research Communications Vol. 309, No. 4, 2003, pp. 1017-1026.
[40] S. Bradamante, L. Barenghi, A. Villa, “Cardiovascular protective effects of resveratrol” Cardiovascular and Drug Reviews Vol. 22, No. 3, 2004, pp. 169-188.
[41] P.S. HRay,H G. HMaulikH, G.A. HCordis, HA.A. HBertelli,H A. HBertelliH, D.K. HDasH, “The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury” HFree Radical Biology and MedHicine Vol. 27, No. 1-2, 1999, pp. 160-169.
[42] O. Ates, S. Cayli, E. Altinoz, I. Gurses, N. Yucel, M. Sener, A. Kocak, S. Yologlu, “HNeuroprotection by resveratrol against traumatic brain injury in rats”H Molecular and Cellular Biochemistry Vol. 294, No. 1-2, 2007, pp. 137-144.
[43] A. HKodeH, S. HRajendrasozhanH, S. HCaitoH, S.R. HYangH, I.L. HMegsonH, I. HRahman, “HResveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells” HAmerican Journal of Physiological Lung Cellular and Molecular PhysiologyH Vol. 294, No. 3, 2008, pp. L478-L488.
[44] S.J. HKimH, R.J. HReiterH, M.V. HRouvier GarayH, W. HQiH, G.H. HEl-SokkaryH, D.X. HTanH “2-Nitropropane-induced lipid peroxidation: antitoxic effects of melatonin” HToxicologyH 130, No. 2-3, 1998, pp. 183-190.

  
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