Hepatoprotective Effect of the Methanolic Leaf Extract of Annona senegalensis Pers. against 7, 12-dimethylbenz[a]anthracene (DMBA)-Induced Toxicity

doi.org/10.26538/tjnpr/v6i3.15

Authors

  • Abiodun H. Adebayo Department of Biochemistry, College of Science and Technology, Covenant University, Canaan Land, Ota PMB1023, Ogun State, Nigeria
  • Osarobo Bakare-Akpata Department of Biochemistry, College of Science and Technology, Covenant University, Canaan Land, Ota PMB1023, Ogun State, Nigeria
  • Omolara F. Yakubu Department of Biochemistry, College of Science and Technology, Covenant University, Canaan Land, Ota PMB1023, Ogun State, Nigeria

Keywords:

Annona senegalensis, Antioxidant, Liver damage, 7,12-dimethylbenz[a]anthracene

Abstract

The liver is critical in the metabolism of 7, 12-dimethylbenz[a]anthracene (DMBA), as a result, DMBA is a strong liver toxin and its hepatotoxicity stems from its conversion to an active carcinogenic metabolite. The study examined the hepatoprotective effect of Annona senegalensis in rats induced with DMBA. Ten rats each in eight groups were used. Animals in group A were used as controls; group B was given 35 mg/kg bwt of DMBA intraperitoneally twice monthly for two months; and animals in groups C, D, E and F were induced and treated with 50, 100 and 200 mg/kg bwt of A. senegalensis and 15 mg/kg bwt rutin, respectively. Furthermore, group G animals were pre-treated with 100 mg/kg bwt of extract daily for two weeks before induction, while group H was administered 200 mg/kg bwt of extract only. Treatments were administered orally for 14 days. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), Malonaldehyde (MDA), creatinine and urea increased (p< 0.05), while reduced glutathione (GSH) level and superoxide dismutase (SOD) activity decreased (p < 0.05) in the induced-only group compared to the extract and rutin administered groups. Treatment with 100 and 200 mg/kg bwt A. senegalensis extract and rutin significantly (p < 0.05) reversed these effects. Histological results showed reduced vascular constrictions in the extract and rutin-treated groups. These results show that the extract of A. senegalensis was able to bring the antioxidant, liver and oxidative stress biomarkers close to normal while ameliorating hepatocellular lesions observed after DMBA induction. 

References

Abbas I, Badran G, Verdin A, Ledoux F, Roumié M, Courcot D, Garçon G. Polycyclic aromatic hydrocarbon

derivatives in airborne particulate matter: sources, analysis and toxicity. Environ Chem Lett. 2018; 16(2):439-475.

Abdel-Shafy HI and Mansour MS. A review on polycyclic aromatic hydrocarbons: source, environmental impact,

effect on human health and remediation. Egypt J Pet. 2016; 25(1):107-123.

Krishnamoorthy D and Sankaran M. Modulatory effect of Pleurotusostreatus on oxidant/antioxidant status in 7, 12-

dimethylbenz (a) anthracene induced mammary carcinoma in experimental rats-A dose-response study. J Cancer Res

Ther. 2016; 12(1):386.

Kerdelhué B, Forest C, Coumoul X. Dimethyl-Benz (a) anthracene: A mammary carcinogen and a neuroendocrine

disruptor. Biochimie Open. 2016; 3:49-55.

Abba MC, Zhong Y, Lee J, Kil H, Lu Y, Takata Y, Simper MS, Gaddis S, Shen J, Aldaz CM. DMBA induced mouse

mammary tumors display high incidence of activating Pik3caH1047 and loss of function Pten mutations. Oncotarget. 2016; 7(39):64289-64299.

Sharifi-Rad M, Anil Kumar NV, Zucca P, Varoni EM, Dini L, Panzarini E, Rajkovic J, TsouhFokou PV, Azzini E, Peluso I, Prakash Mishra A. Lifestyle, oxidative stress, and antioxidants: Back and forth in the pathophysiology of chronic diseases. Front Physiol. 2020; 11:694.

Padureanu R, Albu CV, Mititelu RR, Bacanoiu MV, Docea AO, Calina D, Padureanu V, Olaru G, Sandu RE, Malin

RD, Buga AM. Oxidative stress and inflammation interdependence in multiple sclerosis. J Clin Med. 2019; 8(11):1815.

Tsatsakis AM, Docea AO, Calina D, Buga AM, Zlatian O, Gutnikov S, Kostoff RN, Aschner M. Hormetic Neurobehavioral effects of low dose toxic chemical mixtures in real-life risk simulation (RLRS) in rats. Food Chem Toxicol. 2019; 125:141-149.

Kalra A, Yetiskul E, Wehrle CJ, Tuma F. Physiology, liver. In: Treasure Island (FL): StatPearls Publishing. 2021;Avialable from: https://www.ncbi.nlm.nih.gov/books/NBK535438/

Omeke CP, Udodeme HO, Nwafor FI, EzugwuCO. Antioxidant and hepatoprotective properties from the

extract and fractions of Annona senegalensis Pers (Annonaceae) stem bark grown in Nigeria. Eur J Med Plants. 2019; 28(4):1-13.

Antunes dos Santos A, Ferrer B, Marques Gonçalves F, Tsatsakis AM, Renieri EA, Skalny AV, Farina M, Rocha JB, Aschner M. Oxidative stress in methylmercury-induced cell toxicity. Toxics. 2018; 6(3):47.

Mahajan L, Verma PK, Raina R, Pankaj NK, Sood S, Singh M. Alteration in thiols homeostasis, protein and lipid

peroxidation in renal tissue following subacute oral exposure of imidacloprid and arsenic in Wistar rats. Toxicol Rep. 2018; 5:1114-1119.

Oke GO, Abiodun AA, Imafidon CE, Monsi BF. Zingiberofficinale (Roscoe) mitigates CCl4-induced liver histopathology and biochemical derangements through antioxidant, membrane-stabilizing and tissue-regenerating potentials. Toxicol Rep. 2019; 6:416-425.

Nwafor FI and Orabueze CI. Role of phytochemistry in plant classification: phytochemotaxonomy. In: Egbuna C,

Ifemeje JC, Udedi SC, Kumar S, editors. Phytochemistry, Volume 1: Fundamentals, modern techniques and applications. United Kingdom: Apple Academic Press, 2019; 197p.

Delgado Y, Cassé C, Ferrer-Acosta Y, Suárez-Arroyo IJ, Rodríguez-Zayas J, Torres A, Torres-Martínez Z, Pérez D,

González MJ, Velázquez-Aponte RA, Andino J, CorreaRodríguez C, Franco JC, Milán W, Rosario G, Velázquez E, Vega J, Colón J, Batista C. Biomedical effects of the phytonutrients turmeric, garlic, cinnamon, graviola, and oregano: A comprehensive review. Appl Sci. 2021; 11(18):8477.

Johnson TO, Olatunde A, Nwachukwu L. Phytochemical composition of Annona senegalensis leaf and its antioxidant

activity during Trypanosoma brucei brucei induced oxidative stress in mice. J Pharm Bioresour. 2017; 14(2):219-227.

Ahmed AF, Fatima S, Rasheed A. Herbal flavonoids in treatment of hepatic diseases: A review. World J Pharm

Res. 2019; 8(6):188-197.

Adebayo HA, Zeng GZ, Fan JT, Ji CJ, He WJ, Xu JJ, Zhang YM, Akindahunsi R, Kela AA, Tan NH. Biochemical haematological and histopathological studies of extract of Ageratum conyzoides L. in Sprague Dawley rat. J Med Plants Res. 2010; 4(21):264-2272.

Arora R, Bhushan S, Kumar R, Mannan R, Kaur P, Singh B, Vig AP, Sharma D, Arora S. Hepatic dysfunction induced by 7, 12-dimethylbenz(a)anthracene and its obviation with erucin using enzymatic and histological changes as indicators. PloSOne. 2014; 9(11):e112614.

Reitman S and Frankel A colorimetric method for the determination of serum glutamic oxalacetic and glutamic

pyruvic transaminases. Am J ClinPathol. 1957; 28:56-63.

Schmidt E, Schmidt FW. Determination of GOT and GTP enzyme. Enzymol Biol Et Clin. 1967; 3(1):1-5.

Tietz NW, Rinker AD, Shaw LM. International Federation of Clinical Chemistry. IFCC methods for the measurement

of catalytic concentration of enzymes, part 5. IFCC method for alkaline phosphatase (orthophosphoric-monoester phosphohydrolase, alkaline optimum, EC 3.1.3.1). J Clin Chem Clin Biochem. 1983; 21(11):731-748.

Fawcett JK and Scott JE. A rapid and precise method for the determination of urea. J Clin Pathol. 1960; 13(2):156-

Bartels H, Bohmer, M, Heierli C. Serum creatinine determination without protein precipitation. Clin Chim Acta. 1972; 37:193-197.

Weichselbaum CT. An accurate and rapid method for the determination of proteins in small amounts of blood serum and plasma. Am J Clin Pathol. 1946; 16(3):40-49.

Bakrim S, Motiaa Y, Ouarour A, Masrar A. Hematological parameters of the blood count in a healthy population of

pregnant women in the Northwest of Morocco (TetouanM’diq-Fnideq provinces). Pan Afr Med J. 2018; 29(1):1-12.

Marklund S and Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Clin Chem Clin. 1946; 47(3):469-474.

Prins GK and Loose JA. Glutathione. Biochemical methods in red blood cell genetics Academic Press, London. 1969;

-129.

Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95(2):351-358.

Aliyu R, Adebayo AH, Gatsing D, Garba IH. The effects of ethanolic leaf extract of Commiphora africana (Burseraceae) on rat liver and kidney functions. J Pharmacol Toxicol. 2007; 2(4):373-379.

Zakaria ZA, Kamisan FH, Teh LK, Salleh M. Aqueous partition of methanolic extract of Dicranopteris linearis leaves protect against liver damage induced by paracetamol. Nutr. 2019; 11(12):2945.

Kumar R, Kaur R, Singh AP, Arora S. Diminution of hepatic response to 7, 12-dimethylbenz(a)anthracene by ethyl acetate fraction of Acacia catechu willd through modulation of xenobiotic and anti-oxidative enzymes in rats. PLoS One. 2014; 9(2):e90083.

Dokrory IA, Fahmy RS, Soliman MA, Mohamed SA, Amer AS. Protective and curative effect of sea cucumber Holothuriaatra extract against DMBA-induced hepatorenal diseases in rats. Biomed Res Int. 2015; 2015:1-11.

Estevez M and Xiong Y. Intake of oxidized proteins and amino acids and causative oxidative stress and disease: recent scientific evidences and hypotheses. J Food Sci. 2019; 84(3):387-396.

El Kholy W, Serag H, Zakaria A, El Metwaly A. The potency of some natural products on dimethylbenz(a)anthracene (DMBA) induced hepatotoxicity in rats. Egypt J Hosp Med. 2013; 53(1):1036-1048.

Olafedehan CO, Obun AM, Yusuf MK, Adewumi OO, Oladefedehan AO, Awofolaji AO, Adeniji AA. Effects of residual cyanide in processed cassava peal meals on haematological and biochemical indices of growing rabbits. In Proceedings of 35th Annual Conference of Nigerian Society for Animal Production. 2010. 212 p.

Pittman RN. Regulation of Tissue Oxygenation. San Rafael (CA): Morgan & Claypool Life Sciences; 2011. Chapter 7, Oxygen Transport in Normal and Pathological Situations: Defects and Compensations.

Etim NN, Williams ME, Akpabio U, Offiong EE. Haematological parameters and factors affecting their values. J Agric Sci. 2014; 2(1):37-47.

Moselhy SS. Chemopreventive effect of lycopene alone or with melatonin against the genesis of oxidative stress and mammary tumors induced by 7, 12-dimethylbenz(a)

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Published

2022-05-01

How to Cite

H. Adebayo, A., Bakare-Akpata, O., & F. Yakubu, O. (2022). Hepatoprotective Effect of the Methanolic Leaf Extract of Annona senegalensis Pers. against 7, 12-dimethylbenz[a]anthracene (DMBA)-Induced Toxicity: doi.org/10.26538/tjnpr/v6i3.15. Tropical Journal of Natural Product Research (TJNPR), 6(3), 388–394. Retrieved from https://tjnpr.org/index.php/home/article/view/139