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Effect of Acetyl-l-Carnitine on Antioxidant Status, Lipid Peroxidation, and Oxidative Damage of Arsenic in Rat

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Abstract

Arsenic (As) is a widespread environmental contaminant present around the world in both organic and inorganic forms. Oxidative stress is postulated as the main mechanism for As-induced toxicity. This study was planned to examine the protective effect of acetyl-l-carnitine (ALC) on As-induced oxidative damage in male rats. Animals were randomly divided into four groups of control (saline), sodium arsenite (NaAsO2, 20 mg/kg), ALC (300 mg/kg), and NaAsO2 plus ALC. Animals were dosed orally for 28 successive days. Blood and tissue samples including kidney, brain, liver, heart, and lung were collected on the 28th day and evaluated for oxidative damage and histological changes. NaAsO2 exposure caused a significant lipid peroxidation as evidenced by elevation in thiobarbituric acid-reactive substances (TBARS). The activity of antioxidant enzymes such as glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), as well as sulfhydryl group content (SH group) was significantly suppressed in various organs following NaAsO2 treatment (P < 0.05). Furthermore, NaAsO2 administration increased serum values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and bilirubin. Our findings revealed that co-administration of ALC and NaAsO2 significantly suppressed the oxidative damage induced by NaAsO2. Tissue histological studies have confirmed the biochemical findings and provided evidence for the beneficial role of ALC. The results concluded that ALC attenuated NaAsO2-induced toxicity, and this protective effect may result from the ability of ALC in maintaining oxidant–antioxidant balance.

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References

  1. Cohen SM, Arnold LL, Eldan M, Lewis AS, Beck BD (2006) Methylated arsenicals: the implications of metabolism and carcinogenicity studies in rodents to human risk assessment. Crit Rev Toxicol 36:99–133

    Article  CAS  PubMed  Google Scholar 

  2. Aposhian HV (1997) Enzymatic methylation of arsenic species and other new approaches to arsenic toxicity. Annu Rev Pharmacol Toxicol 37:397–419

    Article  CAS  PubMed  Google Scholar 

  3. Ratnaike RN (2003) Acute and chronic arsenic toxicity. Postgrad Med J 79:391–396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gilman AG, Rall TW, Nies AS, Taylor P (1970) Heavy metals and heavy-metal antagonist. In: The pharmacological basis of therapeutics. McGraw-Hill, New York.

  5. Bates MN, Smith AH, Hopenhayn-Rich C (1992) Arsenic ingestion and internal cancers: a review. Am J Epidemiol 135:462–476

    CAS  PubMed  Google Scholar 

  6. Liu LZ, Jiang Y, Carpenter RL, Jing Y, Peiper SC, Jiang BH (2011) Role and mechanism of arsenic in regulating angiogenesis. PLoS One 6, e20858.

  7. Shi H, Shi X, Liu KJ (2004) Oxidative mechanism of arsenic toxicity and carcinogenesis. Mol Cell Biochem 255:67–78

    Article  CAS  PubMed  Google Scholar 

  8. Kosnett MJ (2013) The role of chelation in the treatment of arsenic and mercury poisoning. J Med Toxicol 9:347–354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Flora SJ, Pachauri V (2010) Chelation in metal intoxication. Int J Environ Res Public Health 7:2745–2788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Calabrese V, Ravagna A, Colombrita C, Scapagnini G, Guagliano E, Calvani M, Butterfield DA, Giuffrida Stella AM (2005) Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: involvement of the transcription factor Nrf2. J Neurosci Res 79:509–521

    Article  CAS  PubMed  Google Scholar 

  11. Rump TJ, Abdul Muneer PM, Szlachetka A M, Lamb A, Haorei C, Alikunju S, Xiong H, Keblesh J, Liu J, Zimmerman MC, Jones J, Donohue TMJr, Persidsky Y, Haorah J (2010) Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain. Free Radic Biol Med 49:1494–1504.

  12. Rebouche CJ (2004) Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann N Y Acad Sci 1033:30–41

    Article  CAS  PubMed  Google Scholar 

  13. Chan A, Shea TB (2007) Effects of dietary supplementation with N-acetyl cysteine, acetyl-L-carnitine and S-adenosyl methionine on cognitive performance and aggression in normal mice and mice expressing human ApoE4. Neruomol Med 9:264–269

    Article  Google Scholar 

  14. Nalecz KA, Miecz D, Berezowski V, Cecchelli R (2004) Carnitine: transport and physiological functions in the brain. Mol Asp Med 25:551–567

    Article  CAS  Google Scholar 

  15. Tandon N, Roy M, Roy S, Gupta N (2012) Protective effect of Psidium guajava in arsenic-induced oxidative stress and cytological damage in rats. Toxicol Int 19:245

    Article  PubMed  PubMed Central  Google Scholar 

  16. Avila J, Barbaro B, Gangemi A, Romagnoli T, Kuechle J, Hansen M, Shapiro J, Testa G, Sankary H, Benedetti E, Lakey J, Oberholzer J (2005) Intra-ductal glutamine administration reduces oxidative injury during human pancreatic islet isolation. Am J Transplant 5:2830–2837

    Article  CAS  PubMed  Google Scholar 

  17. Nili-Ahmadabadi A, Tavakoli F, Hasanzadeh GR, Rahimi HR, Sabzevari O (2011) Protective effect of pretreatment with thymoquinone against aflatoxin B1 induced liver toxicity in mice. Daru 19:282–287

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Marcus CJ, Habig WH, Jakoby WB (1978) Glutathione transferase from human erythrocytes. Nonidentity with the enzymes from liver. Arch Biochem Biophys 188:287–293

    Article  CAS  PubMed  Google Scholar 

  19. Hassani S, Sepand MR, Jafari A, Jaafari J, Rezaee R, Zeinali M, Tavakoli F, Razavi-Azarkhiav K (2014) Protective effects of curcumin and vitamin E against chlorpyrifos-induced lung oxidative damage. Hum Exp Toxicol doi:0960327114550888

  20. Luck H (1965) Catalase. Methods of enzymatic analysis. Academic Press, New York

    Google Scholar 

  21. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  PubMed  Google Scholar 

  22. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  23. Jomova K, Jenisova Z, Feszterova M, Baros S, Liska J, Hudecova D, Rhodes CJ, Valko M (2011) Arsenic: toxicity, oxidative stress and human disease. J Appl Toxicol 31:95–107

    CAS  PubMed  Google Scholar 

  24. Pari L, Mohamed Jalaludeen A (2011) Protective role of sinapic acid against arsenic: induced toxicity in rats. Chem Biol Interact 194:40–47

    Article  CAS  PubMed  Google Scholar 

  25. Nikolaos S, George A, Telemachos T, Maria S, Yannis M, Konstantinos M (2000) Effect of L-carnitine supplementation on red blood cells deformability in hemodialysis patients. Ren Fail 22:73–80

    Article  CAS  PubMed  Google Scholar 

  26. Yousef MI, Omar SA, El-Guendi MI, Abdelmegid LA (2010) Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat. Food Chem Toxicol 48:3246–3261

    Article  CAS  PubMed  Google Scholar 

  27. Del Rio D, Stewart AJ, Pellegrini N (2005) A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 15:316–328

    Article  PubMed  Google Scholar 

  28. Razavi-Azarkhiavi K, Ali-Omrani M, Solgi R, Bagheri P, Haji-Noormohammadi M, Amani N, Sepand MR (2014) Silymarin alleviates bleomycin-induced pulmonary toxicity and lipid peroxidation in mice. Pharm Biol 52:1267–1271

    Article  CAS  PubMed  Google Scholar 

  29. El-Demerdash FM, Yousef MI, Radwan FM (2009) Ameliorating effect of curcumin on sodium arsenite-induced oxidative damage and lipid peroxidation in different rat organs. Food Chem Toxicol 47:249–254

    Article  CAS  PubMed  Google Scholar 

  30. Prabu SM, Muthumani M (2012) Silibinin ameliorates arsenic induced nephrotoxicity by abrogation of oxidative stress, inflammation and apoptosis in rats. Mol Biol Rep 39:11201–11216

    Article  CAS  PubMed  Google Scholar 

  31. Roy S, Bhattacharya S (2006) Arsenic-induced histopathology and synthesis of stress proteins in liver and kidney of Channa punctatus. Ecotoxicol Environ Saf 65:218–229

    Article  CAS  PubMed  Google Scholar 

  32. Hughes MF (2002) Arsenic toxicity and potential mechanisms of action. Toxicol Lett 133:1–16

    Article  CAS  PubMed  Google Scholar 

  33. Meyer AJ, Hell R (2005) Glutathione homeostasis and redox-regulation by sulfhydryl groups. Photosynth Res 86:435–457

    Article  CAS  PubMed  Google Scholar 

  34. Flora SJ (2011) Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 51:257–281

    Article  CAS  PubMed  Google Scholar 

  35. Wu MM, Chiou HY, Wang TW, Hsueh YM, Wang IH, Chen CJ, Lee TC (2001) Association of blood arsenic levels with increased reactive oxidants and decreased antioxidant capacity in a human population of northeastern Taiwan. Environ Health Perspect 109:1011–1017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Liu J, Li C, Qu W, Leslie E, Bonifant CL, Buzard GS, Saavedra JE, Keefer LK, Waalkes MP (2004) Nitric oxide prodrugs and metallochemotherapeutics: JS-K and CB-3–100 enhance arsenic and cisplatin cytolethality by increasing cellular accumulation. Mol Cancer Ther 3:709–714

    CAS  PubMed  Google Scholar 

  37. Karalija A, Novikova LN, Kingham PJ, Wiberg M, Novikov LN (2012) Neuroprotective effects of N-acetyl-cysteine and acetyl-L-carnitine after spinal cord injury in adult rats. PLoS One 7, e41086.

  38. Annadurai T, Vigneshwari S, Thirukumaran R, Thomas PA, Geraldine P (2011) Acetyl-L-carnitine prevents carbon tetrachloride-induced oxidative stress in various tissues of Wistar rats. J Physiol Biochem 67:519–530

    Article  CAS  PubMed  Google Scholar 

  39. Barhwal K, Hota SK, Jain V, Prasad D, Singh SB, Ilavazhagan G (2009) Acetyl-l-carnitine (ALCAR) prevents hypobaric hypoxia-induced spatial memory impairment through extracellular related kinase-mediated nuclear factor erythroid 2-related factor 2 phosphorylation. Neuroscience 161:501–514

    Article  CAS  PubMed  Google Scholar 

  40. Yadav SK, Juwarkar AA, Kumar GP, Thawale PR, Singh SK, Chakrabarti T (2009) Bioaccumulation and phyto-translocation of arsenic, chromium and zinc by Jatropha curcas L.: impact of dairy sludge and biofertilizer. Bioresour Technol 100:4616–4622

    Article  CAS  PubMed  Google Scholar 

  41. Binienda ZK, Ali SF (2001) Neuroprotective role of L-carnitine in the 3-nitropropionic acid induced neurotoxicity. Toxicol Lett 125:67–73

    Article  CAS  PubMed  Google Scholar 

  42. Virmani A, Gaetani F, Imam S, Binienda Z, Ali S (2002) The protective role of l‐carnitine against neurotoxicity evoked by drug of abuse, methamphetamine, could be related to mitochondrial dysfunction. Ann N Y Acad Sci 965:225–232

    Article  CAS  PubMed  Google Scholar 

  43. Traina G, Federighi G, Brunelli M, Scuri R (2009) Cytoprotective effect of acetyl-L-carnitine evidenced by analysis of gene expression in the rat brain. Mol Neurobiol 39:101–106

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant (Project No. 29512) from Vice Chancellor for research, Tehran University of Medical Sciences, Tehran, Iran.

Conflict of Interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran

    Mohammad Reza Sepand, Samin Sabzevari, Ali Reza Kazemi & Omid Sabzevari

  2. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Kamal Razavi-Azarkhiavi & Mohammad Reza Zirak

  3. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Ameneh Omidi

  4. Toxicology and Poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran

    Samin Sabzevari & Omid Sabzevari

Authors
  1. Mohammad Reza Sepand
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  2. Kamal Razavi-Azarkhiavi
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Correspondence to Omid Sabzevari.

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Sepand, M.R., Razavi-Azarkhiavi, K., Omidi, A. et al. Effect of Acetyl-l-Carnitine on Antioxidant Status, Lipid Peroxidation, and Oxidative Damage of Arsenic in Rat. Biol Trace Elem Res 171, 107–115 (2016). https://doi.org/10.1007/s12011-015-0436-y

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  • DOI: https://doi.org/10.1007/s12011-015-0436-y

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