IJAR.2023.204

Type of Article:  Original Research

Volume 11; Issue 4 (December 2023)

Page No.: 8740-8747

DOI: https://dx.doi.org/10.16965/ijar.2023.204

Protective Effect of Centella asiatica on AlCl3 and D-Galactose Induced Hepatotoxicity in Rats through the Alleviation of Oxidative Stress as Demonstrated by Histological Changes in Liver

Thirupathirao. Vishnumukkala 1, 2, Prarthana Kalerammana Gopalakrishna 3, Barani Karikalan 4 , Saravanan Jagadeesan 5, Mohamad Taufik Hidayat B. Baharuldin6, Warren Thomas7, Mohamad Aris Mohd Moklas *8.

1 Lecturer, Department of Anatomy, Human Biology Division, School of Medicine, International Medical University, Kuala Lumpur, Malaysia. ORCiD: 0000-0002-9517-3726

2 Ph.D candidate, Department of Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.

3 Lecturer, Department of Physiology, Human Biology division, School of Medicine, International Medical University, Kuala Lumpur, Malaysia. ORCiD: 0000-0002-1428-5305

4 Associate Professor, Department of Pathology, Faculty of Medicine, Bioscience and Nursing, MAHSA university, Bandar Saujana Putra, Selangor, Malaysia. ORCiD: 0000-0002-5751-346X

5 Associate Professor, Department of Anatomy, School of Medicine, Taylors University, Lakeside Campus, Selangor, Malaysia. ORCiD: 0000-0001-7389-7363

6 Unit of Physiology, Dept.of Preclinical, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia, Kuala Lumpur, Malaysia. ORCiD: 0000-0003-4773-8531

7 Associate Professor, Department of Human Biology, Royal College of Surgeons in Ireland – Medical University of Bahrain, Al Sayh, Muharraq Governate, Kingdom of Bahrain. ORCiD: 0000-0003-2706-1770

8 Associate Professor, Department of Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia. ORCiD: 0000-0002-9282-129X.

Corresponding author: Assoc. Prof. Dr. Mohamad Aris Bin Mohd Moklas. PhD (Nottingham University), Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia. +603-97692783 E-Mail: aris@upm.edu.my

ABSTRACT 

Background: Injury to the liver resulting from drug exposure is known as hepatotoxicity. Drug-induced liver damage is a clinical consequence that can be challenging to recognise, avoid, and manage. After administering Centella asiatica extract to rats that have hepatotoxicity induced by AlCl3 and D-galactose, we evaluated the histopathological alterations in the hepatic tissue and measured the concentration of oxidative and anti-oxidative activity.

Objective: The objective of this study is to investigate the protective benefits of Centella asiatica extract on AlCl3 and D-galactose-induced hepatotoxicity.

Materials and methods:  Male albino Wistar rats were used in this study. Centella asiatica extract (100mg, 200mg and 300mg/kg/day) was given orally to the AlCl3 and D-gal induced hepatotoxic rats for seventy days. At the end of treatment, the liver was harvested and the activity levels of oxidative and antioxidative enzymes were determined.  Histopathological changes in the liver were also documented.

Results: Centella asiatica extract significantly raised the levels of SOD and catalase in liver homogenates, while lowering MDA levels and suppressing histopathological changes such as bridging necrosis, intralobular degeneration, focal necrosis, and fibrosis alterations in the liver.

Conclusion: Centella asiatica extract reduced oxidative stress levels in drug-induced hepatotoxicity by attenuating histological changes and normalising the levels of oxidative stress indicators in the liver.

Keywords: Centella asiatica, Hepatotoxicity, AlCl3, D-galactose, Oxidative stress.

REFERENCES

[1]. Trefts E, Gannon M, Wasserman DH. The liver. Curr Biol [Internet]. 2017;27(21):R1147–51. doi: 10.1016/j.cub.2017.09.019
[2]. Xu Z, Kang Q, Yu Z, Tian L, Zhang J, Wang T. Research on the species difference of the hepatotoxicity of medicine based on transcriptome. Front Pharmacol [Internet]. 2021;12. doi: 10.3389/fphar.2021.647084
[3]. Singh A, Bhat TK, Sharma OP. Clinical Biochemistry of Hepatotoxicity. Clinical Bio-chemistry of Hepatotoxicity JClinic Toxicol Published online. 2011:1–19.
[4]. Gómez-Lechón MJ, Tolosa L, Mt D. Cell-based models to predict human hepatotoxici-ty of drugs. Rev Toxicol. 2014;31(2):149–56.
[5]. Exley C. Human exposure to aluminium. Environ Sci Process Impacts [Internet]. 2013;15(10):1807–16. doi: 10.1039/c3em00374d
[6]. Xu F, Liu Y, Zhao H, Yu K, Song M, Zhu Y, et al. Aluminum chloride caused liver dys-function and mitochondrial energy metabolism disorder in rat. J Inorg Biochem [In-ternet]. 2017;174:55–62. doi: 10.1016/j.jinorgbio.2017.04.016
[7]. Chen Q, Xu W, Wu H, Guang C, Zhang W, Mu W. An overview of D-galactose utiliza-tion through microbial fermentation and enzyme-catalyzed conversion. Appl Micro-biol Biotechnol [Internet]. 2021;105(19):7161–70. doi: 10.1007/s00253-021-11568-5
[8]. Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ. Mecha-nisms of hepatotoxicity. Toxicol Sci [Internet]. 2002;65(2):166–76. doi: 10.1093/toxsci/65.2.166
[9]. Park KS. Pharmacological effects of Centella asiatica on skin diseases: Evidence and possible mechanisms. Evid Based Complement Alternat Med [Internet]. 2021;2021:5462633. doi: 10.1155/2021/5462633
[10]. Jagadeesan S, Musa Chiroma S, Baharuldin MTH, Taib CNM, Amom Z, Adenan MI, et al. Centella asiatica prevents chronic unpredictable mild stress-induced behavioral changes in rats. Biomed Res Ther [Internet]. 2019;6(6):3233–43. doi: 10.15419/bmrat.v6i6.550
[11]. Diniz LRL, Calado LL, Duarte ABS, de Sousa DP. Centella asiatica and its metabolite Asiatic acid: Wound healing effects and therapeutic potential. Metabolites [Internet]. 2023;13(2):276. doi: 10.3390/metabo13020276
[12]. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbi-turic acid reaction. Anal Biochem [Internet]. 1979;95(2):351–8. doi: 10.1016/0003-2697(79)90738-3
[13]. Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem [Internet]. 1972;247(10):3170–5. doi: 10.1016/s0021-9258(19)45228-9
[14]. Chance B, Maehly AC. [136] Assay of catalases and peroxidases. In: Methods in En-zymology. Elsevier; 1955. p. 764–75.
[15]. Kunjumon R, Johnson AJ, Baby S. Centella asiatica: Secondary metabolites, biological activities and biomass sources. Phytomed Plus [Internet]. 2022;2(1):100176. doi: 10.1016/j.phyplu.2021.100176
[16]. Jhansi D, Kola DM. The antioxidant potential of Centella asiatica: A review. Journal of Medicinal Plants Studies. 2019;7(2):18–20.
[17]. Bouasla A, Boumendjel A, Feki AE, Messarah M. Antioxidant Effect of Alpha Lipoic Acid on Hepatotoxicity Induced by Aluminium. 2014.
[18]. Motevalian M, Tekyeh Maroof N, Nematollahi MH, Khajehasani F, Fatemi I. Atorvas-tatin modulates the expression of aging-related genes in the brain of aging induced by D-galactose in mice. Iran J Basic Med Sci [Internet]. 2021;24(10):1388–94. doi: 10.22038/IJBMS.2021.58502.12996
[19]. Koizumi MH, Fujii S, Ono A, Hirose A, Imai T, Ogawa K, et al. Two generation repro-ductive toxicity study of aluminium sulphate in rats. Reprod Toxicol. 2010;31:219–30.
[20]. Zhu Y, Li X, Chen C, Wang F, Li J, Hu C, et al. Effects of aluminium trichloride on the trace elements and cytokines in the spleen of rats. Food Chem Toxicol. 2012;50:2911–5.
[21]. El-Demerdash FM. Antioxidant effect of vitamin E and selenium on lipid peroxida-tion, enzyme activities and biochemical parameters in rats exposed to aluminium. J Trace Elem Med Biol [Internet]. 2004;18(1):113–21. doi: 10.1016/j.jtemb.2004.04.001
[22]. Pritchard MT, Apte U. Models to study liver regeneration. In: Liver Regeneration. Elsevier; 2015. p. 15–40.
[23]. Castellani C, Marai A, Vacchi P. The Centella asiatica. Boll Chim Farm. 1981;120(10):570–605.
[24]. Zainol MK, Abd-Hamid A, Yusof S, Muse R. Antioxitative activity and total phenolic compounds of leaf, root, and petiole of four accessions of Centella asiatica (L.) Ur-ban. Food Chem. 2003;81:575–81.
[25]. Nehru B, Anand P. Oxidative damage following chronic aluminium exposure in adult and pup rat brains. J Trace Elem Med Biol [Internet]. 2005;19(2–3):203–8. doi: 10.1016/j.jtemb.2005.09.004
[26]. Wu Z, Du Y, Xue H, Wu Y, Zhou B. Aluminium induces neuro degeneration and its tox-icity arises from increased iron accumulation and reactive oxygen species (ROS) production. Neurobiol Aging. 2012;33:1–12.
[27]. Newairy A-S, Salama AF, Hm H, Yousef MI. Propolis alleviates aluminium induced li-pid peroxidation and biochemical parameters in male rats. Food Chem Toxicol. 2009;47:1093–8.
[28]. Abdul-Hamid A, Shah Z, Muse R, Mohamed S. Characterization of antioxiclative ac-tivities of various extracts of Centella asiatica (L) Urban. Food chemistry. 2002;77:465–9.
[29]. Chong XQ, Li A, Puah JY, Anamalay KA, Nwabueze Okechukwu P, Chan HK. In vitro an-tioxidant properties and methylglyoxal (MGO) scavenging effects of Centella asiatica leaves in water extract [Internet]. Malaysian Journal of Medicine and Health Scienc-es Mal J Med Health Sci 2022;18(6):183-192.
[30]. Choi M-J, Zheng H-M, Kim JM, Lee KW, Park YH, Lee DH. Protective effects of Centel-la asiatica leaf extract on dimethylnitrosamine-induced liver injury in rats. Mol Med Rep [Internet]. 2016;14(5):4521–8. doi: 10.3892/mmr.2016.5809
[31]. Lu J, Chen C, Gai R, Qiu H, Wu Y, He Q, et al. Protective effects and possible mecha-nisms of Centella asiatica (L.) urban extract against acute and chronic liver injury: Evidence from in vivo and in vitro studies. Phytother Res [Internet]. 2021;35(5):2785–96. doi: 10.1002/ptr.7024
[32]. Mohapatra P, Ray A, Jena S, Nayak S, Mohanty S. Influence of extraction methods and solvent system on the chemical composition and antioxidant activity of Centella asiatica L. leaves. Biocatal Agric Biotechnol [Internet]. 2021;33(101971):101971. doi: 10.1016/j.bcab.2021.101971
[33]. Ferah Okkay I, Okkay U, Aydin IC, Bayram C, Ertugrul MS, Mendil AS, et al. Centella asiatica extract protects against cisplatin-induced hepatotoxicity via targeting oxida-tive stress, inflammation, and apoptosis. Environ Sci Pollut Res Int [Internet]. 2022;29(22):33774–84. doi: 10.1007/s11356-022-18626-z
[34]. Kumar V, Sharma A, Machawal L, Nagarajan K, Siddiqui SA. Effect of Centella asiatica against anti-tuberculosis drugs-induced hepatotoxicity: Involvement of mitochondria and oxidative stress. J Phytopharm [Internet]. 2014;3(5):310–5. doi: 10.31254/phyto.2014.3502
[35]. Jeon SY, Kim MR, Yu SH, Kim MJ, Shim K-S, Shin E, et al. Combined extract of Vitis vinifera L. and Centella asiatica synergistically attenuates oxidative damage induced by hydrogen peroxide in human umbilical vein endothelial cells. Prev Nutr Food Sci [Internet].2020;25(2):173–83. doi: 10.3746/pnf.2020.25.2.173

Cite this article: Thirupathirao. Vishnumukkala, Prarthana Kalerammana Gopalakrishna, Barani Karikalan, Saravanan Jagadeesan, Mohamad Taufik Hidayat B. Baharuldin, Warren Thomas, Mohamad Aris Mohd Moklas. Protective Effect of Centella asiatica on AlCl3 and D-Galactose Induced Hepatotoxicity in Rats through the Alleviation of Oxidative Stress as Demonstrated by Histological Changes in Liver. Int J Anat Res 2023;11(4):8740-8747. DOI: 10.16965/ijar.2023.204