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Effect of l-carnitine on aspartame-induced oxidative stress, histopathological changes, and genotoxicity in liver of male rats

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Published/Copyright: January 15, 2019

Abstract

Background

Aspartame (ASP) is used for treatment of obesity and diabetes mellitus. This study was designed to illustrate the biochemical responses and histopathological alterations besides the genotoxicity of ASP alone or with l-carnitine (LC) in the liver of rats.

Methods

Animals were separated into six groups: control, lower dose of ASP (ASP-LD; 75 mg/kg), higher dose of ASP (ASP-HD; 150 mg/kg), l-carnitine (LC; 10 mg/kg), ASP-LD plus LC, and ASP-HD plus LC. Treatment was carried out orally for 30 consecutive days.

Results

ASP raised the activity of some enzymes of liver markers and disturbed the lipid profile levels. The hepatic reduced glutathione (GSH) levels, the marker enzymes of antioxidant activities, were obviously diminished, and, possibly, the lipid peroxidation, C-reactive protein, and interleukins levels were increased. ASP significantly increased the DNA deterioration in comparison with the control in a dose-dependent manner. LC prevented ASP-induced liver damage as demonstrated by the enhancement of all the above parameters. Results of histopathological and electron microscopic examination proved the biochemical feedback and the improved LC effect on liver toxicity.

Conclusions

The co-treatment of LC showed different improvement mechanisms against ASP-induced liver impairment. So, the intake of ASP should be regulated and taken with LC when it is consumed in different foods or drinks to decrease its oxidative stress, histopathology, and genotoxicity of liver.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Alleva R, Borghi B, Santarelli L, Strafella E, Carbonari D, Bracci M, et al. In vitro effect of aspartame in angiogenesis induction. Toxicol In Vitro 2011;25:286–93.10.1016/j.tiv.2010.09.002Search in Google Scholar

2. Choudhary AK, Devi RS. Serum biochemical responses under the oxidative stress of aspartame in Wistar albino rats. Asian Pac J Trop Dis 2014;4:403–10.10.1016/S2222-1808(14)60478-3Search in Google Scholar

3. Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol 1997;82:291–5.10.1113/expphysiol.1997.sp004024Search in Google Scholar PubMed

4. Yakubu MT, Bilbis LS, Lawal M, Akanji MA. Effect of repeated administration of sildenafil citrate on selected enzyme activities of liver and kidney of male albino rats. Nig J Pure Appl Sci 2003;18:1395–400.Search in Google Scholar

5. Hamza RZ, Ismail HA, El-Shenawy NS. Oxidative stress, histopathological and electron microscopic alterations induced by dimethylnitrosamine in renal male mice and the protective effect of α-lipoic acid. J Basic Clin Physiol Pharmacol 2017;28:149–58.10.1515/jbcpp-2016-0042Search in Google Scholar PubMed

6. Yılmaz S, Uçar A. A review of the genotoxic and carcinogenic effects of aspartame: does it safe or not? Cytotechnology 2014;66:875–81.10.1007/s10616-013-9681-0Search in Google Scholar PubMed PubMed Central

7. Keskin E, Uluisik D, Altin M. Antioxidant effect of L-carnitine in rats fed cholesterol-rich diet. Anim Vet Sci 2015;3:113–6.10.11648/j.avs.20150304.13Search in Google Scholar

8. Rani PJ, Panneerselvam C. Effect of L-carnitine on brain lipid peroxidation and antioxidant enzymes in old rats. J Gerontol A Biol Sci Med Sci 2002;57:134–7.10.1093/gerona/57.4.B134Search in Google Scholar

9. Yapar K, Kart A, Karapehlivan M, Atakisi O, Tunca R, Erginsoy S, et al. Hepatoprotective effect of L-carnitine against acute acetaminophen toxicity in mice. Exp Toxicol Pathol 2007;59:121–8.10.1016/j.etp.2007.02.009Search in Google Scholar PubMed

10. Panneerselvam KS, Kumaran S. l-Carnitine, and alpha-lipoic acid improve mitochondrial function during aging process. Clin Nutr 2006;21:48–60.10.1016/j.clnu.2006.02.005Search in Google Scholar

11. Yildirim R, Yildirim A, Dane S, Aliyev E, Yigitoglu R. Dose-dependent protective effect of L-carnitine on oxidative stress in the livers of hyperthyroid. Eurasian J Med 2013;45:1–6.10.5152/eajm.2013.01Search in Google Scholar PubMed PubMed Central

12. Saluk-Juszczak J, Olas B, Wachowicz B, Glowacki R, Bald E. L-carnitine modulates blood platelet oxidative stress. Cell Biol Toxicol 2010;26:355–65.10.1007/s10565-009-9148-4Search in Google Scholar PubMed

13. Canbolat EP, Sağsöz N, Noyan V, Yücel A, Kisa Ü. Effects of L-carnitine on oxidative stress parameters in oophorectomized rats. Alexan J Med 2017;53:55–60.10.1016/j.ajme.2016.02.002Search in Google Scholar

14. Iyyaswamy A, Rathinasamy S. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats. J Biosci 2012;37:679–88.10.1007/s12038-012-9236-0Search in Google Scholar

15. Elshazly SA, Ahmed MM, Hassan EH, Ibrahim ZS. Protective effect of L-carnitine against ᵞ-rays irradiation-induced tissue damage in mice. Am J Biochem Mol Biol 2012;2:120–32.10.3923/ajbmb.2012.120.132Search in Google Scholar

16. King J. The transferases alanine and aspartate transaminases. In: King J, editor. Practical clinical enzymology. London: Van Nostrand Company Limited, 1965:121–38.Search in Google Scholar

17. Reitman S, Frankel SA. Colorimetric method for the determination of serum glutamic oxyacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28:56–63.10.1093/ajcp/28.1.56Search in Google Scholar

18. Young DC, Koon HR, Hyung KC. In vitro and in vivo experimental effect of Korean red ginseng on erection. J Urol 1999;162:1508–11.10.1016/S0022-5347(05)68349-8Search in Google Scholar

19. Orlowski M, Meister A. Isolation of gamma-glutamyl transpeptidase from hog kidney. J Biol Chem 1965;240:338–47.10.1016/S0021-9258(18)97654-4Search in Google Scholar

20. Bowers LD, Wong ET. Kinetic serum creatinine assays. II. A critical valuation and review. Clin Chem 1980;26:555–61.10.1093/clinchem/26.5.555Search in Google Scholar

21. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–54.10.1016/0003-2697(76)90527-3Search in Google Scholar

22. Carr T, Andressen CJ, Rudel LL. Enzymatic determination of triglyceride, free cholesterol and total cholesterol in tissue lipid extracts. Clin Chem 1993;26:39–42.10.1016/0009-9120(93)90015-XSearch in Google Scholar

23. Warnick GR, Benderson J, Albers JJ. Selected methods of clinical chemistry. Am Assoc Clin Chem 1983;10:91–9.Search in Google Scholar

24. Friedewald WT. Estimation of concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 1972;18:499–502.10.1093/clinchem/18.6.499Search in Google Scholar

25. El-Shenawy NS, El-Salmy F, Al-Eisa RA, El-Ahmary B. Amelioratory effect of vitamin E on organophosphorus insecticide diazinon-induced oxidative stress in mice liver. Pest Biochem Physiol 2010;96:101–710.1016/j.pestbp.2009.09.008Search in Google Scholar

26. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1970;95:351–8.10.1016/0003-2697(79)90738-3Search in Google Scholar

27. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974;47:469–74.10.1111/j.1432-1033.1974.tb03714.xSearch in Google Scholar

28. Aebi H. Catalase in vitro. Meth Enzymol 1984;105:121–6.10.1016/S0076-6879(84)05016-3Search in Google Scholar

29. Hafeman DG, Sunde RA, Hoekstra WG. Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat. J Nutrit 1974;104:580–7.10.1093/jn/104.5.580Search in Google Scholar

30. Suzuki K, Ota H, Sasagawa S, Sakatani T, Fujikura T. Assay method for myeloperoxidase in human polymorphonuclear leukocytes. Anal Biochem 1983;132:345–52.10.1016/0003-2697(83)90019-2Search in Google Scholar

31. Litwack G, Bothwell JW, Williams JN, Elvehjem CA. A colorimetric assay for xanthine oxide in rat liver homogenates. J Biol Chem 1953;200:303–10.10.1016/S0021-9258(18)38465-5Search in Google Scholar

32. Couri D, Abdel-Rahman MS. Effect of chlorine dioxide and metabolites on the glutathione-dependent system in rat, mouse and chicken blood. J Environ Pathol Toxicol 1980;3:451–60.Search in Google Scholar

33. Wener MH, Daum PR, McQuillin GM. The influence of age, sex, and race on the upper reference limit of serum C-reactive protein concentration. J Rheumatol 2000;27:2351–9.Search in Google Scholar

34. Drury RA, Wallington EA. Carleton’s histological techniques, 5th ed. Oxford, UK: Oxford University Press, 1980.Search in Google Scholar

35. Gupta PD. Ultrastructural study on semithin section. Sci Tools 1983;30:6–7.Search in Google Scholar

36. Collins AR, Dunsinka M. Oxidation of cellular DNA measured with the comet assay. In: Armstrong D, editor. Methods in molecular biology: oxidative stress biomarkers and antioxidant protocols. New Jersy: Humana Press, 2002:147–59.10.1385/1-59259-173-6:147Search in Google Scholar

37. Liu T, Lu J, Wang Y, Campbell WA, Huang L, Zhu J, et al. Computerized image analysis for quantitative neuronal phenotyping in zebrafish. J Neurosci Methods 2005;153:190–202.10.1016/j.jneumeth.2005.10.024Search in Google Scholar PubMed

38. Abdallah IZ. Physiological changes induced by long-term administration of saccharin compared with aspartame to male Albino rats. Egypt J Hosp Med 2000;8:70–81.10.21608/ejhm.2002.18747Search in Google Scholar

39. Abhilash M, Sauganth PM, Varghese MV, Nair RH. Effect of long-term intake of aspartame on antioxidant defense status in liver. Food Chem Toxicol 2011;49:1203–7.10.1016/j.fct.2011.02.019Search in Google Scholar

40. Evans M, Khan N, Rees A. Diabetic dyslipidemia and coronary heart disease. New perspectives. Curr Opin Lipidol 1999;10:387–91.10.1097/00041433-199910000-00002Search in Google Scholar

41. Prokić MD, Paunović MG, Matić MM, Djordjević NZ, Ognjanović BI, Štajn AŠ, et al. Effect of aspartame on biochemical and oxidative stress parameters in rat blood. Arch Biol Sci Belgrade 2015;67:535–45.10.2298/ABS141009016PSearch in Google Scholar

42. Mourad IM. Effect of aspartame on some oxidative stress parameters in liver and kidney of rats. Afr J Pharm Pharmacol 2011;5:678–82.10.5897/AJPP10.302Search in Google Scholar

43. Bhattacharjee R, Sil PC. The protein fraction of Phyllanthus niruri plays a protective role against acetaminophen-induced hepatic disorder via its antioxidant properties. Phytother Res 2006;20:595–601.10.1002/ptr.1933Search in Google Scholar

44. Castro GD, Costantini MH, Delgado de layno AM, Castro JA. Rat liver microsomal and nuclear activation of methanol to hydroxyl methyl free radicals. Toxicol Lett 2002;129:227–36.10.1016/S0378-4274(02)00021-8Search in Google Scholar

45. Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn GL, et al. Aspartame: a review of safety. Regul Toxicol Pharmacol 2002;35:S1–93.10.1006/rtph.2002.1542Search in Google Scholar PubMed

46. Dobrzynska I, Skrzydlewska E, Kasacka I, FigaszewskiZ. Protective effect of N-acetylcysteine on rat liver cell membrane during methanol intoxication. J Pharm Pharmacol 2000;52:547–52.10.1211/0022357001774183Search in Google Scholar PubMed

47. El Haliem NG, Mohamed DS. The effect of aspartame on the histological structure of the liver and renal cortex of adult male albino rat and the possible protective effect of Pimpinella anisum oil. Egypt J Histol 2011;34:715–26.10.1097/01.EHX.0000406589.05585.8dSearch in Google Scholar

48. Ju C, Reilly TP, Bourdi M, Radonovich MF, Brady JN, George JW, et al. Protective role of Kupffer cells in acetaminophen-induced hepatic injury in mice. Chem Res Toxicol 2002;15:1504–13.10.1021/tx0255976Search in Google Scholar PubMed

49. Basseri S, Austin RC. Endoplasmic reticulum stress and lipid metabolism. Mechanisms and therapeutic potential biochemistry research international. Biomed Res Int 2012;2012:13. Article ID 841362.10.1155/2012/841362Search in Google Scholar

50. Lin WM, Baker AC, Beroukhim R. Modeling genomic diversity and tumor dependency in malignant melanoma. Cancer Res 2008;68:664–73.10.1158/0008-5472.CAN-07-2615Search in Google Scholar

51. Bandyopadhyay A, Ghoshal S, Mukherjee A. Genotoxicity testing of low-calorie sweeteners: aspartame, acesulfame-K, and saccharin. Drug Chem Toxicol 2008;31:447–57.10.1080/01480540802390270Search in Google Scholar

52. Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X, Fernandez Lopez JA, et al. Formaldehyde derived from dietary aspartame binds to tissue components in vivo. Life Sci 1998;63:337–49.10.1016/S0024-3205(98)00282-3Search in Google Scholar

Received: 2018-04-05
Accepted: 2018-11-15
Published Online: 2019-01-15

©2019 Walter de Gruyter GmbH, Berlin/Boston

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