Anti-inflammation effect of Apium graveolens Extract against lead-acetate-induced brain injury in rats

  • Sona Sulistyo Student of Postgraduate Biomedical Sciences Program, Faculty of Medicine, Universitas Sumatra Utara, Medan, North Sumatra, Indonesia
  • Hadi Sarosa Department of Postgraduate Biomedical Science, Medical Faculty, Sultan Agung Islamic University (UNISSULA), Semarang, Central Java, Indonesia
  • Titiek Sumarawati Department of Postgraduate Biomedical Science, Medical Faculty, Sultan Agung Islamic University (UNISSULA), Semarang, Central Java, Indonesia
  • Agung Putra Department of Postgraduate Biomedical Science, Medical Faculty, Sultan Agung Islamic University (UNISSULA), Semarang, Central Java, Indonesia
  • Chodidjah Chodidjah Department of Postgraduate Biomedical Science, Medical Faculty, Sultan Agung Islamic University (UNISSULA), Semarang, Central Java, Indonesia
  • Nur Dina Amalina Biological Sciences Division, Nara Institute of Science and Technology, Japan
  • Sugeng Ibrahim Faculty of Medicine, Soegijapranata Catholic University, Semarang, Indonesia
Keywords: Apium graveolens extract, TNF-α, Caspase-3, Lead acetate, brain injury

Abstract

Purpose: The current study investigated the protective potential of Apium graveolens extract (APE) against lead-induced brain injury in rats by exploring anti-inflammatory and antiapoptotic mechanism. Methods:  Twenty male Wistar rats were randomly allocated into four groups (n=5). The control group was orally administrated with distillate water. The second group received lead acetate 200mg/kg body weight orally for 14 days, the third group were orally administered lead acetate 200 mg lead acetate/kg body weight and vitamin E 50IU/kg body weight for 14 days. The fourth group was administrated with leas acetate like second group and APE 300mg/kg body weight for 14 days. The TNF-a levels and caspase-3 expression was analyses under ELISA and flow cytometry assay, respectively. Results: The phytochemical analysis of APE indicated the presence of alkaloids, flavonoids, tannins, saponins, and steroids. Leads acetate increased the serum levels of TNF-α and caspase-3 expression, as well as altering the brain tissue architecture. Conclusion: In conclusion, the presence of APE inhibited the lead acetate toxicity by inhibition of TNF-α proinflammation protein and caspase-3 proapoptosis protein.

References

1. Farkhondeh T, Boskabady M, Koohi M, Sadeghi-Hashjin G, Moin M. The Effect of Lead Exposure on Selected Blood Inflammatory Biomarkers in Guinea pigs. Cardiovascular & Hematological Disorders-Drug Targets. 2013;13(1):45–9.

2. WHO. The Toxic Truth Children’s Exposure to Lead Pollution Undermines a Generation of Future Potential. 2012;232.

3. Fewtrell LJ, Prüss-Üstün A, Landrigan P, Ayuso-Mateos JL. Estimating the global burden of disease of mild mental retardation and cardiovascular diseases from environmental lead exposure. Environmental Research. 2004;94(2):120–33.

4. Wani AL, Ara A, Usmani JA. Lead toxicity: A review. Interdiscip Toxicol. 2015;8(2):55–64.

5. Ramírez Ortega D, González Esquivel DF, Blanco Ayala T, Pineda B, Gómez Manzo S, Marcial Quino J, et al. Cognitive impairment induced by lead exposure during lifespan: Mechanisms of lead neurotoxicity. Toxics. 2021;9(2):1–30.

6. Zarei MH, Pourahmad J, Aghvami M, Soodi M, Nassireslami E. Lead acetate toxicity on human lymphocytes at non-cytotoxic concentrations detected in human blood. Main Group Metal Chemistry. 2017;40(5–6):105–12.

7. Abdel Moneim AE, Dkhil MA, Al-Quraishy S. Effects of flaxseed oil on lead acetate-induced neurotoxicity in rats. Biological Trace Element Research. 2011;144(1–3):904–13.

8. Kumar Singh P, Kumar Singh M, Singh Yadav R, Kumar Dixit R, Mehrotra A, Nath R. Attenuation of Lead-Induced Neurotoxicity by Omega-3 Fatty Acid in Rats. Annals of Neurosciences. 2018;24(4):221–32.

9. Huang Y, Liao Y, Zhang H, Li S. Lead exposure induces cell autophagy via blocking the akt/mtor signaling in rat astrocytes. Journal of Toxicological Sciences. 2020;45(9):559–67.

10. Faletti L, Peintner L, Neumann S, Sandler S, Grabinger T, Mac Nelly S, et al. TNFα sensitizes hepatocytes to FasL-induced apoptosis by NFκB-mediated Fas upregulation. Cell Death and Disease. 2018;9(9).

11. Furuichi K, Kokubo S, Hara A, Imamura R, Wang Q, Kitajima S, et al. Fas Ligand Has a Greater Impact than TNF-α on Apoptosis and Inflammation in Ischemic Acute Kidney Injury. Nephron Extra. 2012;2(1):27–38.

12. Ashafaq M, Tabassum H, Vishnoi S, Salman M, Raisuddin S, Parvez S. Tannic acid alleviates lead acetate-induced neurochemical perturbations in rat brain. Neuroscience Letters. 2016;617:94–100.

13. Wang Y, Wang SQ, Cui WH, He JJ, Wang ZF, Yang XL. Olive leaf extract inhibits lead poisoning-induced brain injury. Neural Regeneration Research. 2013;8(22):2021–9.

14. Kooti W, Daraei N. A Review of the Antioxidant Activity of Celery (Apium graveolens L). Journal of Evidence-Based Complementary and Alternative Medicine. 2017;22(4):1029–34.

15. Sofowora A, Ogunbodede E, Onayade A. The role and place of medicinal plants in the strategies for disease prevention. African journal of traditional, complementary, and alternative medicines : AJTCAM / African Networks on Ethnomedicines. 2013;10(5):210–29.

16. Mursiti S, Amalina ND, Marianti A. Inhibition of breast cancer cell development using Citrus maxima extract through increasing levels of Reactive Oxygen Species (ROS). J Phys Conf Ser. 2021;1918(5).

17. Amalina ND, Wahyuni S, Harjito. Cytotoxic effects of the synthesized Citrus aurantium peels extract nanoparticles against MDA-MB-231 breast cancer cells. J Phys Conf Ser. 2021;1918(3).

18. Safira A, Savitri SL, Putri ARB, Hamonangan JM, Safinda B, Solikhah TI, et al. Review on the pharmacological and health aspects of Hylocereus or Pitaya: An update. Journal of Drug Delivery and Therapeutics. 2021;11(6):297–303.

19. Mahendra R, Rofik A, Salim HM, Ulfa M, Awwaliyah ES. Neuroprotective Activity of Extract of Celery (Apium Graveolens) in Insilico Study. Medical and Health Science Journal. 2021;5(2):27–31.

20. Li P, Jia J, Zhang D, Xie J, Xu X, Wei D. In vitro and in vivo antioxidant activities of a flavonoid isolated from celery (Apium graveolens L. var. dulce). Food and Function. 2014;5(1):50–6.

21. Naushad M, Urooj M, Ahmad T, Husain GM, Kazmi MH, Zakir M. Nephroprotective effect of Apium graveolens L. against Cisplatin-induced nephrotoxicity. Journal of Ayurveda and Integrative Medicine. 2021;12(4):607–15.

22. Köken T, Koca B, Özkurt M, Erkasap N, Kuş G, Karalar M. Apium graveolens Extract Inhibits Cell Proliferation and Expression of Vascular Endothelial Growth Factor and Induces Apoptosis in the Human Prostatic Carcinoma Cell Line LNCaP. Journal of Medicinal Food. 2016;19(12):1166–71.

23. Suzery M, Cahyono B, Amalina ND. Antiproliferative and apoptosis effect of hyptolide from Hyptis pectinata ( L .) Poit on human breast cancer cells. 2020;10(02):1–6.

24. Amalina ND, Suzey M, Cahyono B. Cytotoxic Activity of Hyptis pectinata Extracts on MCF-7 Human Breast Cancer Cells. Indonesian Journal of Cancer Chemoprevention. 2020;02(February):1–6.

25. Cahyono B, Suzery M, Amalina ND, Bima DN. Synthesis and antibacterial activity of epoxide from hyptolide ( Hyptis pectinata ( L .) Poit ) against Gram-positive and Gram- negative bacteria. 2020;10(12):13–22.

26. Hermansyah D, Putra A, Munir D, Lelo A, Amalina ND, Alif I. Synergistic Effect of Curcuma longa Extract in Combination with Phyllanthus niruri Extract in Regulating Annexin A2 , Epidermal Growth Factor Receptor , Matrix Metalloproteinases , and Pyruvate Kinase M1 / 2 Signaling Pathway on Breast Cancer Stem Cell. 2021;9:271–85.

27. Fernanda MAHF, Andriani RD, Estulenggani Z, Kusumo GG. Identification and Determination of Total Flavonoids in Ethanol Extract of Old and Young Angsana Leaves (Pterocarpus indicus Willd.) Using Visible Spectrophotometry. In Scitepress; 2019. p. 541–4.

28. Y R, Y I, M.S I. Comparative Phyto-Constituents Analysis from the Root Bark and Root Core Extractives of Cassia ferruginea (Schrad D. C) Plant. Scholars Journal of Agriculture and Veterinary Sciences. 2016 Jul;3(4):275–83.

29. Sri Sulasmi E, Saptasari M, Mawaddah K, Ama Zulfia F. Tannin identification of 4 species pterydophyta from baluran national park. In: Journal of Physics: Conference Series. Institute of Physics Publishing; 2019.

30. Adu JK, Amengor CDK, Kabiri N, Orman E, Patamia SAG, Okrah BK. Validation of a Simple and Robust Liebermann-Burchard Colorimetric Method for the Assay of Cholesterol in Selected Milk Products in Ghana. Int J Food Sci. 2019;2019.

31. Pękal A, Pyrzynska K. Evaluation of Aluminium Complexation Reaction for Flavonoid Content Assay. Food Anal Methods. 2014 Sep 1;7(9):1776–82.

32. Suzery M, Cahyono B, Amalina ND. Citrus sinensis (L) peels extract inhibits metastasis of breast cancer cells by targeting the downregulation matrix metalloproteinases-9. Open Access Maced J Med Sci. 2021;9(B):464–9.

33. Amalina ND, Wahyuni S, Harjito. Cytotoxic effects of the synthesized Citrus aurantium peels extract nanoparticles against MDA-MB-231 breast cancer cells. J Phys Conf Ser. 2021;1918(3):032006.

34. Prasad Raju Borelli D, Raju P, Tirumanyam Sri Padmavati Mahila Visvavidyalayam M, Sushma Nannepaga Sri Padmavati Mahila Visvavidyalayam J. IDENTIFICATION OF BIOACTIVE COMPOUNDS BY FTIR ANALYSIS AND IN VITRO ANTIOXIDANT ACTIVITY OF CLITORIA TERNATEA LEAF AND FLOWER EXTRACTS I am working on rare earth ions doped glasses and glad ceramics View project Thermal and optical properties of glasses doped with rare earths and nanoparticles View project [Internet]. 2014. Available from: www.iajpr.com

35. Lidsky TI, Schneider JS. Lead neurotoxicity in children: Basic mechanisms and clinical correlates. Brain. 2003;126(1):5–19.
36. di Penta A, Moreno B, Reix S, Fernandez-Diez B, Villanueva M, Errea O, et al. Oxidative Stress and Proinflammatory Cytokines Contribute to Demyelination and Axonal Damage in a Cerebellar Culture Model of Neuroinflammation. PLoS One. 2013 Feb 19;8(2).

37. Samarghandian S, Borji A, Afshari R, Delkhosh MB, Gholami A. The effect of lead acetate on oxidative stress and antioxidant status in rat bronchoalveolar lavage fluid and lung tissue. Toxicology Mechanisms and Methods. 2013;23(6):432–6.

38. Boskabady M, Marefati N, Farkhondeh T, Shakeri F, Farshbaf A, Boskabady MH. The effect of environmental lead exposure on human health and the contribution of inflammatory mechanisms, a review. Environ Int [Internet]. 2018;120(July):404–20. Available from: https://doi.org/10.1016/j.envint.2018.08.013

39. Abdel-Daim MM, Alkahtani S, Almeer R, Albasher G. Alleviation of lead acetate-induced nephrotoxicity by Moringa oleifera extract in rats: highlighting the antioxidant, anti-inflammatory, and anti-apoptotic activities. Environmental Science and Pollution Research. 2020;27(27):33723–31.

40. James Offor S, Orji Mbagwu H, Ebere Orisakwe O. Improvement of Lead Acetate-Induced Testicular Injury and Sperm Quality Deterioration by Solanum Anomalum Thonn. Ex. Schumach Fruit Extracts in Albino Rats. Journal of Family & Reproductive Health. 2019;13(2).

41. Kayode I, Olugbenga I. Lead Acetate Induced Cerebral Tissue Damage; The Effect of Phoenix dactylifera Pits Extract. European Journal of Medicinal Plants. 2017;21(2):1–9.
42. Chibowska K, Baranowska-Bosiacka I, Falkowska A, Gutowska I, Goschorska M, Chlubek D. Effect of lead (Pb) on inflammatory processes in the brain. International Journal of Molecular Sciences. 2016;17(12).

43. Arauz J, Ramos-Tovar E, Muriel P. Redox state and methods to evaluate oxidative stress in liver damage: From bench to bedside. Annals of Hepatology. 2016;15(2):160–73.

44. Salehi F, Behboudi H, Kavoosi G, Ardestani SK. Oxidative DNA damage induced by ROS-modulating agents with the ability to target DNA: A comparison of the biological characteristics of citrus pectin and apple pectin. Scientific Reports. 2018;8(1):1–16.

45. Ginwala R, Bhavsar R, Chigbu DGI, Jain P, Khan ZK. Potential role of flavonoids in treating chronic inflammatory diseases with a special focus on the anti-inflammatory activity of apigenin. Antioxidants. 2019;8(2):1–30.

46. Tiwari AK. Imbalance in antioxidant defence and human diseases: Multiple approach of natural antioxidants therapy. Vol. 81, REVIEW ARTICLES CURRENT SCIENCE. 2001.

47. Brunetti C, di Ferdinando M, Fini A, Pollastri S, Tattini M. Flavonoids as antioxidants and developmental regulators: Relative significance in plants and humans. Vol. 14, International Journal of Molecular Sciences. 2013. p. 3540–55.

48. Hao J, Lou P, Han Y, Zheng L, Lu J, Chen Z, et al. Ultraviolet-B Irradiation Increases Antioxidant Capacity of Pakchoi (Brassica rapa L.) by Inducing Flavonoid Biosynthesis. Plants. 2022 Mar 1;11(6).

49. Bajpai VK, Baek KH, Kang SC. Antioxidant and free radical scavenging activities of taxoquinone, a diterpenoid isolated from Metasequoia glyptostroboides. South African Journal of Botany. 2017 Jul 1;111:93–8.

50. Aly O, Abouelfadl DM, Shaker OG, Hegazy GA, Fayez AM, Zaki HH. Hepatoprotective effect of Moringa oleifera extract on TNF-α and TGF-β expression in acetaminophen-induced liver fibrosis in rats. Egyptian Journal of Medical Human Genetics. 2020;21(1).

51. Putra A, Antari AD, Kustiyah AR, Intan YSN, Sadyah NAC, Wirawan N, et al. Mesenchymal stem cells accelerate liver regeneration in acute liver failure animal model. Biomedical Research and Therapy. 2018;5(11):2802–10.

52. Hamra NF, Putra A, Tjipta A, Amalina ND, Nasihun T. Hypoxia mesenchymal stem cells accelerate wound closure improvement by controlling α-smooth muscle actin expression in the full-thickness animal model. Open Access Maced J Med Sci. 2021;9:35–41.
Published
2024-12-10
How to Cite
Sulistyo, S., Sarosa, H., Sumarawati, T., Putra, A., Chodidjah, C., Amalina, N. D., & Ibrahim, S. (2024). Anti-inflammation effect of Apium graveolens Extract against lead-acetate-induced brain injury in rats. International Journal of Cell and Biomedical Science, 2(6), 182-191. https://doi.org/10.59278/cbs.v2i6.41
Section
Articles

Most read articles by the same author(s)