Skip to main content

Advertisement

SpringerLink
Log in

The cardioprotective effects of L-carnitine on rat cardiac injury, apoptosis, and oxidative stress caused by amethopterin

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

09 April 2024 Editor's Note: Readers are alerted that the concerns have been raised with this article. Editorial action will be taken as appropriate once this matter is resolved and all parties have been given an opportunity to respond in full.

Abstract

Amethopterin is used as a chemotherapeutic agent, and its antioxidant activity is used to treat many cancer types. This study aimed to study the ameliorating effect of L-carnitine against amethopterin-induced cardiac injury and oxidative stress in male rats. Sixty male albino rats were equally divided into six groups; the first and second groups were the control and L-carnitine groups, respectively, while the third group was treated with amethopterin rat group; the fourth and fifth groups were co-treated and post-treated with amethopterin rat with L-carnitine, respectively, and the sixth group was self-treated with amethopterin rat group. Cholesterol, triglycerides, low-density lipoprotein (LDL), glutathione, and total protein levels in amethopterin group showed a significant decrease when compared with control group, while high-density lipoprotein (HDL), glutamic oxaloacetic transaminase (GOT), malondialdehyde (MDA), catalase, and nitric oxide (NO) levels in amethopterin group showed a significant increase when compared with control group. Cholesterol, triglycerides, LDL, GOT, MDA, and catalase levels in the self-treated group showed a significant increase when compared with amethopterin group, while glutathione, total protein, and NO levels in the self-treated group showed significant decrease when compared with amethopterin group. Many of abnormalities as moderate hydrophobic changes of myofibrillar structure with striations, myocardial atrophy, cytoplasmic vacuoles, edema, and leukocyte infiltration were detected in cardiac tissues in amethopterin rat group. A significant increase of the apoptotic protein p53 and CD68 immunoreactivity, despite a significant decrease in the antiapoptotic Bcl–2 proteins after amethopterin injection when compared with control group, was observed. Treatment (co and post) with L-carnitine improved the biochemical, histopathological, and immunohistochemical alterations in the heart treated with amethopterin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Change history

  • 09 April 2024

    Editor's Note: Readers are alerted that the concerns have been raised with this article. Editorial action will be taken as appropriate once this matter is resolved and all parties have been given an opportunity to respond in full.

References

  • Aebi H (1984) Catalase. In: HU B (ed) Methods of enzymatic analysis. Academic Press, New York, pp. 673–684

  • ALL C, Ertan B, Ergul BK et al (2006) N-acetylcysteine ameliorate methotrexate-induced oxidative liver damage in rats. Med Sci Monit 12(8):247–248

  • Babiak M, Campello AP, Carnieri EG et al (1998) Methotrexate: pentose cycle and oxidative stress. Cell Biochem Funct 16:283–293

  • Bancroft JD, Cook HC (1994) Manual of histological techniques and their diagnostic application. Churchill Livingstone, Edinburgh, London, New York, Tokyo, pp 23–26

    Google Scholar 

  • Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888

    CAS  Google Scholar 

  • Cetin A, Kaynar L, Kocyigit I et al (2008) Role of grape seed extract on methotrexate induced oxidative stress in rat liver. Am J Chin Med 36:1–12

  • Chan ES, Montesinos MC, Fernandez P (2006) Adenosine A (2A) receptors play a role in the pathogenesis of hepatic cirrhosis. Br J Pharmacol 148(8):1144–1155

  • Ciralik H, Bulbuloglu E, Cetinkaya A et al (2006) Effects of N acetylcysteine on methotrexate induced small intestinal damage in rats. Mt Sinai J Med 73:1086–1092

  • Collavin L, Lunardi A, Del-Sal G (2010) P43-family proteins and their regulators: hubs and spokes in tumor suppression. Cell Death Differ 17:901–911

    Article  CAS  Google Scholar 

  • Cory S, Huang CSD, Adams MJ (2003) The bcl-2 family: roles in cell survival and oncogenesis. Oncogene 22:8590–8607

  • Dokmeci D (2005) Oxidative stress, male infertility and the role of carnitines. Folia Med (Plovdiv) 47:26–30

    Google Scholar 

  • El-Demerdash FM, Abbady EA, Baghdadi HH (2016) Oxidative stress modulation by Rosmarinus officinalis in creosote-induced hepatotoxicity. Environ Toxicol 31:85–92

    Article  CAS  Google Scholar 

  • Georgiadis AN, Papavasiliou EC, Lourida ES et al (2006) Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment—a prospective, controlled study. Arthritis Res Ther 8(3):82–88

  • Giovana AC et al. (2016) Bioadhesive surfactant systems for methotrexate skin delivery. Molecules 21:231. doi:10.3390/molecules21020231

  • Grube R, Kelm M et al (1994) The biology of nitric oxide. Enzymology, biochemistry, and immunology. Portland Press, London, pp 201–204

  • Hyeong SK et al. (2016) Chemotherapy in elderly patients with gastric cancer. J Cancer 7(1):88–94

    Article  Google Scholar 

  • Jahovic N, Sener G, Cevic H et al (2004) Amelioration of methotrexate-induced enteritis by melatonin in rats. Cell Biochem Funct 22:169–178

  • Lowry OH (1951) Protein measurement with folin phenol reagent. J Biol Chem 193:265–275

    Article  CAS  Google Scholar 

  • Iyyaswamy A, Rathinasamy S (2012) ). Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats. Biosci 37:679–688

    CAS  Google Scholar 

  • Muralikrishnan G, Amalan SV, Pillai KS (2001) Dual role of vitamin C on lipid profile and combined application of cyclophosphamide, methotrexate and 5-fluorouracil treatment in fibrosarcoma-bearing rats. Cancer Lett 169:115–120

    Article  CAS  Google Scholar 

  • Osterne R, Matos-Brito R, Alves AP et al (2009) Oral granulocytic sarcoma: a case report. Med Oral Patol Oral Cir Bucal 14(5):232–235

  • Ozogula B, Kisaoglua A, Turanb M et al (2013) The effect of mirtazapine on methotrexate-induced toxicity in rat liver. Sci Asia 39:356–336

  • Rebouche CJ, Seim H (1998) Carnitine metabolism and its regulation in microorganisms and mammals. Annu Rev Nutr 18:39–61

    Article  CAS  Google Scholar 

  • Saggu S, Kumar R (2007) Modulatory effect of sea buckthorn leaf extract on oxidative stress parameters in rats during exposure to cold, hypoxia and restraint (C-H-R) stress and post stress recovery. J Pharm Pharmacol 59(12):1739–1745

    Article  CAS  Google Scholar 

  • Salama AF, Kasem SM, Tousson E et al (2012) Protective role of L-carnitine and vitamin E on the kidney of atherosclerotic rats. Biomed Aging Pathol 2:212–215

  • Salama A, Kasem S, Tousson E et al (2015) L-carnitine and vitamin E alleviate reproductive toxicity caused by triton WR 1339 in male albino rats. Toxicol Ind Health 31(5):467–474

  • Scorrano L, Korsmeyer SJ (2003) Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochem Biophys Res Commun 304(3):437–444

    Article  CAS  Google Scholar 

  • Sener G, Demiralp EE, Cetiner M et al (2006a) L-carnitine ameliorates methotrexate-induced oxidative organ injury and inhibits leukocyte death. Cell Biol Toxicol 22:47–60

  • Sener G, Demiralp EE, Etiner M et al (2006b) B-glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects. Eur J Pharmacol 542:170–178

  • Tousson E, Rafat B, Hessien M et al (2011a) P53 and Bcl2 apoptosis proteins in meso-2,3-dimercaptosuccinic acid (DMSA) treated lead intoxicated rabbits. Toxicol Ind Health 27(3):271–278

  • Tousson E, Alm-Eldeen A, El-Moghazy M (2011b) p53 and bcl-2expression in response to boldenone induced liver cells injury. Toxicol Ind Health 27(8):711–718

  • Tousson E, Beltagy DM, Abo Gazia M et al (2012) Expressions of P53 and CD68 in mouse liver with Schistosoma mansoni infection and the protective role of silymarin. Toxicol Ind Health. doi:10.1177/0748233712442733

  • Tousson E, Hafez E, Zaki S et al (2014a) P53, bcl-2 and CD68 expression in response to amethopterin-induced lung injury and ameliorating role of L-carnitine. Biomed Pharmacother 8(5):631–639

  • Tousson E, Hegazy M, Hafez E et al (2014b) The effect of L-carnitine on amethopterin-induced toxicity in rat large intestine. J Cancer Res Treat 2(3):55–63

  • Tousson E, Tawfeek Z, Abu-Shaeir WA et al (2014c) Methotrexate-induced hepatic and renal toxicity: role of L-carnitine in treatment. Biomed Biotechnol 2(4):85–92

  • Tousson E, Atteya E, El-Atrash E et al (2014c) Abrogation by Ginkgo Byloba leaf extract on hepatic and renal toxicity induced by methotrexate in rats. J Cancer Res Treat 2(3):44–51

  • Tsurusawa M, Saeki K, Fujimoto T (1997) Differential induction of apoptosis on human lymphoblastic leukemia Nalm-6 and molt-4 cells by various antitumor drugs. Int J Hematol 66:79–88

    Article  CAS  Google Scholar 

  • Vardi N, Parlakpinar H, Ozturk F et al (2008) Potent protective effect of apricot and b-carotene on methotrexate induced intestinal oxidative damage in rats. Food Chem Toxicol 46:3015–3022

  • Wielinga P, Hooijberg JH, Gunnarsdottir S, et al. (2005) The human multidrug resistance protein MRP5 transports folates and can mediate cellular resistance against antifolates. Cancer Res 65:4425–4430

    Article  CAS  Google Scholar 

  • Yuan Chen D, Hui-Min C, Joung-Liang L et al (2011) Blood lipid profiles and peripheral blood mononuclear cell cholesterol metabolism gene expression in patients with and without methotrexate treatment. BMC Med 9:4

Download references

Author information

Authors and Affiliations

  1. Zoology Department, Faculty of Science, Tanta University, El-Baher Street, Tanta, 31527, Egypt

    Ehab Tousson, Ezar Hafez, Somia Zaki & Amani Gad

Authors
  1. Ehab Tousson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ezar Hafez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Somia Zaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amani Gad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ehab Tousson.

Additional information

Responsible editor: Philippe Garrigues

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tousson, E., Hafez, E., Zaki, S. et al. The cardioprotective effects of L-carnitine on rat cardiac injury, apoptosis, and oxidative stress caused by amethopterin. Environ Sci Pollut Res 23, 20600–20608 (2016). https://doi.org/10.1007/s11356-016-7220-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-016-7220-1

Keywords

Search

Navigation