Abstract
Liver is the major site for several xenobiotics metabolism, and formation of toxic metabolites that may be hepatotoxic, therefore the burden of metabolism and exposure to dangerous chemicals make liver vulnerable to a variety of disorders. Our work aimed to investigate the effects of some antioxidants such as lipoic acid (LA), S-adenosyl methionine (SAM) and vitamin E in a trail to investigate the possibility of using these substances to relieve and protect liver from exposure to monocrotaline (MCT). Twenty-five mature adult rats were classified into five groups (five rats in each group), control group, MCT-induced hepatic damage, LA+MCT, SAM+MCT and vitamin E+MCT group. Homogenates of liver samples were used for measuring the oxidative biomarkers and hepatic antioxidant status. The results showed that administration of vitamin E, SAM and LA caused a significant increase in liver glutathione contents, glutathione reductase, glutathione peroxidase and glutathione-S-transferase activities and a significant decrease in hepatic catalase and superoxide dismutase. We could conclude that administration of natural LA, SAM and vitamin E before and after MCT injection modulate the hepatic oxidative stresses induced by MCT in various extents.
Acknowledgments
We are thankful to university grant commission, Beni Suef University, Beni Suef, Egypt for providing financial support.
Competing interests
The authors declare that they have no competing interests.
Ethical approval: Committee for postgraduate studies, Beni Suef University College approved the study.
Authors’ contributions
All authors carried out experimental work, biochemical and statistical analysis, interpretation and discussion of the results and wrote the paper related to their part of the work. All authors read and approved the final manuscript.
References
1. FuPP, XiaQ, LinG, ChouMW. Pyrrolizidine alkaloids genotoxicity, metabolism enzymes, metabolic activation, and mechanisms. Drug Metab Rev2004;36:1–55.10.1081/DMR-120028426Search in Google Scholar
2. YangYC, YanJ, DoergeDR, ChanPC, FuPP, ChouMW. Metabolic activation of the tumorigenic pyrrolizidine alkaloid, riddelliine, leading to DNA adduct formation in vivo. Chem Res Toxicol2001;14:101–9.10.1021/tx000150nSearch in Google Scholar
3. GordonGJ, ColemanWB, GrishamJW. Bax-mediated apoptosis in the livers of rats after partial hepatectomy in the retrorsine model of hepatocellular injury. Hepatology2000;32:312–20.10.1053/jhep.2000.9144Search in Google Scholar
4. JozaN, SusinSA, DaugasE, StanfordWL, ChoSK, LiCY. Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature2001;410:549–54.10.1038/35069004Search in Google Scholar
5. MitchellC, MalletVO, GuidottiJE, GoulenoKC, KahnA, GilgenkrantzH. Liver repopulation by Bcl-x (L) transgenic hepatocytes. Am J Pathol2002;160:31–5.10.1016/S0002-9440(10)64345-3Search in Google Scholar
6. RaddatzG, BisswangerH. Receptor site and stereospecificity of dihydrolipoamide dehydrogenase for R- and S-lipoamide: a molecular modeling study. J Biotechnol1997;58:89–100.10.1016/S0168-1656(97)00135-1Search in Google Scholar
7. NesbittNM, CicchilloRM, LeeKH, GroveTL, BookerSJ. Lipoic acid biosynthesis. In: PackerL, PatelM, editors. Alpha lipoic acid: energy production, antioxidant activity and health effects, Chapter 2. Boca Raton, FL: Taylor & Francis,2008:349–71.Search in Google Scholar
8. MarchesiniS, PoirierY. Futile cycling of intermediates of fatty acid biosynthesis toward peroxisomal beta-oxidation in Saccharomyces cerevisiae. J Biol Chem2003;278:32596–601.10.1074/jbc.M305574200Search in Google Scholar PubMed
9. BottiglieriT. S-adenosyl-L-methionine (SAMe): From the bench to the bedside-molecular basis of a pleiotrophic molecule. Am Clin Nutr2002;76:1151S–7.10.1093/ajcn/76.5.1151SSearch in Google Scholar
10. MatoJM, LuS. Role of S-adenosyl-L-methionine in liver health and injury. Hepatology2007;45:1306–12.10.1002/hep.21650Search in Google Scholar PubMed
11. AndreescuC, MulsantBH, EmanuelJE. Complementary and alternative medicine in the treatment of bipolar disorder-a review of the evidence. Affect Disord2008;110:16–26.10.1016/j.jad.2008.03.015Search in Google Scholar PubMed
12. MischoulonD, FavaM. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am Clin Nutr2002;76:1158S–1161S.10.1093/ajcn/76.5.1158SSearch in Google Scholar
13. WatsonWH, ZhaoY, ChawlaRK. S-Adenosylmethionine attenuates the lipopolysaccharide-induced expression of the gene for tumour necrosis factor α. Biochem J1999;342:21–5.10.1042/bj3420021Search in Google Scholar
14. CorralesFP, OchoaC, RivasM, Martin-LomasJ, MatoM, PajaresMA. Inhibition of glutathione synthesis in the liver leads to S-adenosyl-L-methionine synthetase reduction. Hepatology1991;14:528–33.10.1016/0270-9139(91)90194-ZSearch in Google Scholar
15. NikiE, KawakamiA, SaitoM, YamamotoY, TsuchiyaJ, KamiyaY. Effect of phytyl side chain of vitamin E on its antioxidant activity. J Biol Chem1985;260:2191–6.10.1016/S0021-9258(18)89536-9Search in Google Scholar
16. BurtonGW, Le PageY, GabeEJ, IngoldKU. Antioxidant activity of vitamin E and related phenols. Importance of stereo electronic factors. J Am Chem Soc1980;102:7791–2.10.1021/ja00546a032Search in Google Scholar
17. PerlyB, SmithICP, HughesL, BurtonGW, IngoldKU. Autoxidation of biological molecules. Biochim Biophys Acta1985;819:131–5.Search in Google Scholar
18. BryanCL, PatriciaEG, RobertAR. Liver inflammation during MCT hepatotoxicity. Toxicol2003;190:155–69.10.1016/S0300-483X(03)00164-1Search in Google Scholar
19. LiuTY, ChenY, WangZY, JiLL, WangZT. Pyrrolizidine alkaloid isoline induced oxidative injury in various mouse tissues. Exp Toxicol Pathol2010;62:251–7.10.1016/j.etp.2009.04.008Search in Google Scholar
20. Soto-BlancoB, MedeirosRMT, GuerraJL, GorniakSL. Lack of protective action of cysteine against the fetotoxic effect of monocrotaline. Food Chem Toxicol2001;39:635–9.10.1016/S0278-6915(01)00013-8Search in Google Scholar
21. GlowazSL, MichnikaM, HuxtableRJ. Detection of a reactive pyrrole in the hepatic metabolism of the pyrrolizidine alkaloid, monocrotaline. Toxicol Appl Pharmacol1992;115:168–73.10.1016/0041-008X(92)90320-RSearch in Google Scholar
22. YanCC, HuxtableJR. The relationship between the concentration of the pyrrolizidine alkaloids, monocrotaline and the pattern of metabolites released from the isolated liver. Toxicol Appl Pharmacol1995;130:1–8.10.1006/taap.1995.1001Search in Google Scholar PubMed
23. PanLC, WilsonDW, LaméMW, JonesAD, SegallHJ. COR pulmonale is caused by monocrotaline and dehydromonocrotaline, but not by glutathione or cysteine conjugates of dihydropyrrolizine. Toxicol Appl Pharmacol1993;118:87–97.10.1006/taap.1993.1013Search in Google Scholar
24. YanCC, HuxtableRJ. Effect of the pyrrolizidine alkaloid, monocrotaline, on bile composition of the isolated, perfused rat liver. Life Sci1995;57:617–26.10.1016/0024-3205(95)00312-TSearch in Google Scholar
25. NigraL, HuxtableRJ. Hepatic glutathione concentrations and the release of pyrrolic metabolites of the pyrrolizidine alkaloid, monocrotaline, from the isolated perfused liver. Toxicon1992;30:1195–202.10.1016/0041-0101(92)90435-8Search in Google Scholar
26. ArthurJR. The glutathione peroxidases. Cell Mol Life Sci2000;57:1825–35.10.1007/PL00000664Search in Google Scholar PubMed
27. BocchettiR, RegoliF. Seasonal variability of oxidative biomarkers, lysosomal parameters, metallothioneins and peroxisomal enzymes in the Mediterranean mussel Mytilus galloprovincialis from Adriatic Sea. Chemosphere2006;65:913–21.10.1016/j.chemosphere.2006.03.049Search in Google Scholar PubMed
28. LeeCP, ShihPH, HsuCL, YenGC. Hepatoprotection of tea seed oil (Camellia oleifera Abel.) against CCl4-induced oxidative damage in rats. Food Chem Toxicol2007;45:888–95.10.1016/j.fct.2006.11.007Search in Google Scholar PubMed
29. TakaokaM, OhkitaM, KobayashiY, YubaM, MatsumuraY. Protective effect of alpha-lipoic acid against ischaemic acute renal failure in rats. Clin Exp Pharmacol Physiol2002;29:189–94.10.1046/j.1440-1681.2002.03624.xSearch in Google Scholar PubMed
30. AmudhaG, JosephineA, MythiliY, SundarapandiyanR, VaralakshmiP. Therapeutic efficacy of DL-alpha-lipoic acid on cyclosporine A induced renal alterations. Eur J Pharmacol2007;571:209–14.10.1016/j.ejphar.2007.05.047Search in Google Scholar PubMed
31. WiniarskaK, MalinskaD, SzymanskiK, DudziakM, BrylaJ. Lipoic acid ameliorates oxidative stress and renal injury in alloxan diabetic rabbits. Biochimie2008;90:450–9.10.1016/j.biochi.2007.11.010Search in Google Scholar PubMed
32. BilskaA, KrvczvkA, WlodckL. The different aspects of the biological role of glutathione. Postepy Hig Med Dosw2007;61:438–53.Search in Google Scholar
33. AlegreVS, BaroneJM, YamasakiSC, Zambotti-VillelaL, SilveiraPF. Lipoic acid effects on renal function, aminopeptidase activities and oxidative stress in Crotalus durissus terrificus envenomation in mice. Toxicon2010;56:402–10.10.1016/j.toxicon.2010.04.003Search in Google Scholar PubMed
34. PackerL, WittEH, TritschlerHJ. alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med1995;19:227–50.10.1016/0891-5849(95)00017-RSearch in Google Scholar
35. HanD, TritschlerHJ, PackerL. α-Lipoic acid increases intracellular glutathione in a human T-lymphocyte jurkat cell line. Biochem Biophys Res Commun1995;207:258–64.10.1006/bbrc.1995.1181Search in Google Scholar
36. MaritimAC, SandersRA, WatkinsJB. Effects of α-lipoic acid on biomarkers of oxidative stress in streptozotocin-induced diabetic rats. J Nutr Biochem2003;14:288–94.10.1016/S0955-2863(03)00036-6Search in Google Scholar
37. AvilaMA, García-TrevijanoER, Martínez-ChantarML, LatasaMU, Pérez-MatoI, Martínez-CruzLA, et al. S-Adenosylmethionine revisited: its essential role in the regulation of liver function. Alcohol2002;27:163–7.10.1016/S0741-8329(02)00228-8Search in Google Scholar
38. CederbaumAI. Hepatoprotective effects of S-adenosyl-L-methionine against alcohol- and cytochrome P450 2E1-induced liver damage. World J Gastroenterol2010;16:1366–76.10.3748/wjg.v16.i11.1366Search in Google Scholar PubMed PubMed Central
39. LieberCS. S-adenosyl-L-methionine: its role in the treatment of liver disorders. Am J Clin Nutr2002;76:1183S–7.10.1093/ajcn/76.5.1183SSearch in Google Scholar
40. LotkovaH, ZuzanaC, Ervinkova OttoK, PavlaK, RomanK. Protective effect of S-adenosylmethionine on cellular and mitochondrial membranes of rat hepatocytes against tert-butylhydroperoxide-induced injury in primary culture. Chem Biol Interact2005;156:13–23.10.1016/j.cbi.2005.06.008Search in Google Scholar PubMed
41. Munoz-CastañedaJR, TúnezI, HerenciaC, RanchalI, GonzálezR, RamírezLM, et al. Melatonin exerts a more potent effect than S-adenosyl-L-methionine against iron metabolism disturbances, oxidative stress and tissue injury induced by obstructive jaundice in rats. Chem Biol Interact2008;174:79–87.10.1016/j.cbi.2008.05.016Search in Google Scholar PubMed
42. RezkBM, HaenenGR, Van der VijghWJ, BastA. The extraordinary antioxidant activity of vitamin E phosphate. Biochim Biophys Acta2004;1683:16–21.10.1016/j.bbalip.2004.03.005Search in Google Scholar PubMed
43. BayesB, PastorMC, BonalJ, JuncaJ, RomeroR. Homocysteine and lipid peroxidation in hemodialysis: role of folinic acid and vitamin E. Nephrol Dial Transpl2001;16:2172–5.10.1093/ndt/16.11.2172Search in Google Scholar PubMed
44. ShireenKF, PaceM, MahboobA, KhanT. Effects of dietary vitamin E, C and soybean oil supplementation on antioxidant enzyme activities in liver and muscles of rats. Food Chem Toxicol2008;46:3290–4.10.1016/j.fct.2008.07.015Search in Google Scholar PubMed
©2014 by Walter de Gruyter Berlin / Boston
