Synergistic, Attenuative and Modulatory activity in Dimethylnitrosamine (DMN)-induced fibrotic rats treated with Vernonia amygdalina and Annona muricata leaves

Main Article Content

Usunobun Usunomena
Ngozi Paulinus Okolie

Abstract

This study assessed the effect of Vernonia amygdalina and Annona muricata leaves on oxidative stress and extracellular matrix induced by dimethylnitrosamine (DMN) - induced liver fibrosis. Control group received physiological saline; Second group received 100mg/kg each of Vernonia amygdalina and Annona muricata ethanol leaf extract without DMN orally for 14 consecutive days. Third group received 10mg DMN/kg (intraperitoneally) thrice weekly for two weeks, in addition to 100mg/kg each of Vernonia amygdalina and Annona muricata administered for 14 days consecutively while the last group received only 10mg DMN/kg. At the end of administration, the rats were sacrificed, blood samples collected and sera analysed for hyaluronic acid (HA), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), alanine transaminase (ALT), aspartate transaminase (AST) and total protein (TP) while collagen, catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were assayed in liver tissue homogenate. DMN administration caused significant increases in ALP, AST, HA, ALT, LDH and in liver total collagen content and MDA (p < 0.05) and decreased TP, CAT, GSH and SOD. However 100mg/kg Vernonia amygdalina and Annona muricata leaves attenuated and modulated DMN-induced changes thus giving credence that the leaves possess fibro-suppressant, anti-oxidant and anti-hepatotoxic properties against DMN-induced hepatic fibrosis.

Downloads

Download data is not yet available.

Article Details

How to Cite
Usunomena, U. ., & Okolie, N. P. (2020). Synergistic, Attenuative and Modulatory activity in Dimethylnitrosamine (DMN)-induced fibrotic rats treated with Vernonia amygdalina and Annona muricata leaves. Nigerian Journal of Pharmaceutical and Applied Science Research, 9(3), 1–6. Retrieved from https://nijophasr.net/index.php/nijophasr/article/view/349
Section
Articles
Author Biographies

Usunobun Usunomena

Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medical Sciences, Edo University Iyamho, Edo State, Nigeria

Ngozi Paulinus Okolie

Department of Biochemistry, Faculty of Life Sciences. University of Benin, Edo State, Nigeria

References

Adeyemi D, Komolafe O, Adewole S, Obuotor EM, Adenowo T (2008). Antihyperglycemic activities of Annona muricata. Afr. J. Tradit. Complement. Altern. Med 6:62–69

Atangwho IJ, Ebong PE, Eyong EU, Williams IO, Eteng MU, Egbung GE (2009). Comparative chemical composition of leaves of some antidiabetic medicinal plants: Azadirachta indica, Vernonia amygdalina and Gongronema latifolium. Afr. J. Biotechnology 8(18):4685–4689.

Bansal AK, Bansal M, Soni G, Bhatnagar D (2005). Protective role of Vitamin E pre-treatment on N-nitrosodiethylamine induced oxidative stress in rat liver. Chem. Biol. Interact 156(2-3):101-111.

Chang FR (2001). Novel cytotoxic annonaceous acetogenins from Annona muricata. J. Nat. Productivity 64:925–931.

Chichibu K, Matsuura T, Shichijo S (1989). Assay of serum hyaluronic acid in clinical application. Clinica Chimica Acta, 181: 317-324.

Cohen G, Dembiec D, Marcus J (1970). Measurement of catalase activity in tissues. Analyt Biochem. 34:30-38.

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

Farombi EO, Owoeye O (2011). Antioxidant and chemopreventive properties of Vernonia amygdalina and Garcinia biflavonoid. Int. J. Env. Res. Pub. Health 8: 2533–2555.

Fraser JRE, Laurent TC, Laurent UBG (1997). Hyaluronan: its nature, distribution, functions and turnover. J. Internal Med. 242(1) : 27-33.

George J, Chandrakasan G. (2000). Biochemical abnormalities during the progression of hepatic fibrosis induced by dimethylnitrosamine. Clin. Biochem. 33(7):563-570.

George J, Rao KR, Stern R, Chandrakasan G (2001). Dimethyl-nitrosamine-induced liver injury in rats: the early deposition of collagen. Toxicology 156(2-3): 129-138.

George J (2006). Mineral metabolism in dimethylnitrosamine-induced hepatic fibrosis. Clin. Biochem 39: 984–991.

George J (2003). Ascorbic acid concentrations in dimethylnitrosamine-induced hepatic fibrosis in rats, Clin. Chim. Acta 335: 39–47.

Halliwell B, Gutteridge JMC (1995). The definition and measurement of antioxidants in biological systems. Free Radic. Biol. Med 18: 125-126.

Hong SW, Jung KH, Zheng HM, Lee HS, Suh JK, Park IS, Lee DH, Hong SS (2010). The protective effect of resveratrol on dimethylnitrosamine-induced liver fibrosis in rats. Arch. Pharm. Res 33(4):601–609.

Igile GO, Oleszek W, Jurzysta M, Burda S, Fanfunso M, Fasanmade AA (1994). Flavonoids from Vernonia amygdalina and their antioxidant activities. J. Agric. Food Chem. 42: 2445–2448.

Liaw CC, Chang FR, Lin CY, Chou CJ, Chiu HF, Wu MJ, Wu YC. (2002). New cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata. J. Nat. Productivity 65: 470–475.

Iimuro Y, Fujimoto J. (2003). Strategy of gene therapy for liver cirrhosis and hepatocellular carcinoma. J. Hepatobiliary Pancreat. Surg. 10(1): 45-47.

Misra HP, Fridovich I. (1972). The role of superoxide ion in the autooxidation of epinephrine and a simple assay of superoxide dismutase. J. Biol. Chem 247: 3170– 3175.

Mu YP, Liu P, Liu Y, Li FH, Chen GF, Gu HT, Du GL, Wang L, Wang CS (2006). Inhibiting action of Xiayuxue decoction on hepatic fibrosis at progressive stage in rats and study on the prescription and syndrome. J. Tradit. Chin. Med. 47: 215-218

Ohkawa H, Ohishi N, Yogi K (1979). Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Annals Biochem 95: 351–358.

Poli G (2000). Pathogenesis of liver fibrosis: role of oxidative stress. Mol. Aspects Med. 21: 49–98.

Priya S, Vijayalakshmi P, Vivekanandan P, Karthikeyan S (2011a). N-Acetylcysteine attenuates dimethylnitrosoamine induced oxidative stress in rats. European Journal of Pharmacology 654: 181–186.

Priya S, Vijayalakshmi P, Vivekanandan P, Karthikeyan S (2011b). Influence of N-acetylcysteine against dimethylnitrosoamine induced hepatotoxicity in rats. Toxicol. Ind. Health 27(10): 914–922.

Qing-Wei H, Geng-Tao L (2006). Effects of bicyclol on dimethylnitrosamine-induced liver fibrosis in mice and its mechanism of action. Life Science 79: 606–612.

Rojkind M, Giambrone MA, Biempica L (1979). Collagen types in normal and cirrhotic liver. Gastroenterology 76:710–719.

Sharma V, Singh, M (2014). Attenuation of N-nitrosodimethylamine induced hepatotoxicity by Operculina turpethum in Swiss Albino mice. Iranian J. Basic Med. Science 17:73-80.

Shin M, Moon J (2010). Effect of dietary supplementation of grape skin and seeds on liver fibrosis induced by dimethylnitrosamine in rats. Nutri. Res. Pract. 4(5):369- 374.

Shimizu I, Ma YR, Mizobuchi Y (1999). Effects of Sho-saikoto, a Japanese herbal medicine, on hepatic fibrosis in rats. Hepatology 29: 149–160.

Takahashi JA, Pereira CR, Pimenta LP, Boaventura MA, Silva LG (2006). Antibacterial activity of eight Brazilian Annonaceae plants. Nat. Prod. Res 20(1): 21-26.

Usunobun U, Okolie NP (2015a). Phytochemical analysis and mineral composition of Annona muricata leaves. Int. J. Res. Curr. Development 1(1): 38-42.

Usunobun U, Okolie NP (2015b). Phytochemical, trace and mineral composition of Vernonia amygdalina leaves. Int. J. Biol. Pharmaceut. Res. 6(5): 393-399.

Usunobun U, Okolie PN (2016). Phytochemical analysis and proximate composition of Vernonia amygdalina. Int. J. Sci. World 4(1):11 -14.

Usunobun U, Okolie NP, Eze IG. (2015a). Attenuation of N, N-Dimethylnitrosamine -induced liver Fibrosis in rats by ethanolic leaf extract of Annona muricata. Saudi J. Med. Pharmaceut. Science 1(2): 62-69.

Usunomena U, Okolie NP, Eze IG (2015b) Inhibitory Effect of Vernonia amygdalina on Dimethylnitrosamine (DMN)- induced Liver Fibrosis in Rats. Int. J. Clin. Pharmacol. Toxicol., 4(4) : 179-184.

Usunobun U, Anyanwu OG, Okolie PN (2016). Anti-anemic Effect of Annona muricata Ethanolic Leaf Extract in Dimethyl Nitrosamine (DMN)-Induced Hepatic Fibrosis in Rats. EC Pharmacology and Toxicology 2.2 : 91-95.

Vimal V, Devaki T (2004). Hepatoprotective effect of allicin on tissue defense system in galactosamine/endotoxin challenged rats. J. Ethnopharmacology 90: 151–154

Vendemiale G, Grattagliano I, Caruso ML, Serviddio G, Valentini AM, Pirrelli M, Altomare E (2001). Increased oxidative stress in dimethylnitrosamine-induced liver fibrosis in the rat: effect of N-acetylcysteine and interferon-alpha. Toxicol. Appl. Pharmacology 175: 130-9.

Vogel AI (1971). A textbook of practical organic Chemistry including qualitative organic analysis. Longman group limited, London. p426.

Wang JH, Shin JW, Son JY, Cho JH, Son CG (2010). Antifibrotic effects of CGX, a traditional herbal formula, and its mechanisms in rats. J. Ethnopharmacol 127: 534–542.

Yan W, Juncha G, Di Z, Jian Z, Junji M, Huiqing J (2010). New insights into the antifibrotic effects of sorafenib on hepatic stellate cells and liver fibrosis. J. Hepatology 53: 132–144

Yuan GJ, Zhang ML, Gong ZJ (2004). Effect of PPAR agonist pioglitazone on rat hepatic fibrosis. World J. Gastroenterology 10: 1047–1051.