An Indian Desert Shrub ‘Hiran Chabba’, Farsetia hamiltonii Royle, Exhibits Potent Antioxidant and Hepatoprotective Effect Against Iron- Overload Induced Liver Toxicity in Swiss Albino Mice

Author(s): Tapasree Basu, Bipul Kumar, Anil K. Shendge, Sourav Panja, Heerak Chugh, Hemant K. Gautam*, Nripendranath Mandal*.

Journal Name: Current Drug Discovery Technologies

Volume 16 , Issue 2 , 2019

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Abstract:

Background: Farsetia hamiltonii Royle, also known as Hiran Chabba grows in desert regions. It is widely used as folk medicine to treat joint pains, diarrhea and diabetes. However, its antioxidant and iron chelation abilities both in vitro and in vivo have not yet been investigated.

Methods: The 70% methanolic extract of F. hamiltonii (FHME) was investigated for its free radical scavenging and iron chelation potential, in vitro. An iron-overload situation was established by intraperitoneal injection of iron-dextran in Swiss albino mice, followed by oral administration of FHME. Liver damage and serum parameters due to iron-overload were measured biochemically and histopathologically to test iron-overload remediation and hepatoprotective potential of FHME. Phytochemical analyses were performed to determine its probable bioactive components.

Results: FHME showed promising antioxidant activity, scavenged various reactive oxygen and nitrogen species and chelated iron in vitro. FHME reduced liver iron, serum ferritin, normalized serum parameters, reduced oxidative stress in liver, serum and improved liver antioxidant status in ironoverloaded mice. It also alleviated liver damage and fibrosis as evident from biochemical parameters and morphological analysis of liver sections. The phytochemical analyses of FHME reflected the presence of alkaloids, phenols, flavonoids and tannins. HPLC analysis indicated presence of tannic acid, quercetin, methyl gallate, catechin, reserpine, ascorbic acid and gallic acid.

Conclusion: Based on the experimental outcome, FHME, an ethnologically important plant can be envisaged as excellent antioxidant and iron chelator drug capable of remediating iron-overload induced hepatotoxicity and the bioactive compounds present in FHME might be responsible for its efficacy.

Keywords: Farsetia hamiltonii royle, reactive oxygen species, iron chelator, serum ferritin, liver fibrosis, HPLC.

[1]
Ponka P. Cellular iron metabolism. Kidney Int 1999; 55: S2-S11.
[2]
Halliwell B, Gutteridge JMC. Oxygen toxicity, oxygen radicals, transitionmetals and disease. Biochem J 1984; 219: 1-14.
[3]
Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J 2012; 5: 9-19.
[4]
Jomova K, Valko M. Advances in metal-induced oxidative stress and human disease. Toxicology 2011; 283: 65-87.
[5]
Uchiyama A, Kim JS, Kon K, et al. Translocation of iron from lysosomes into mitochondria is a key event during oxidative stress-induced hepatocellular injury. Hepatology 2008; 48: 1644-54.
[6]
Rauen U, Petrat F, Sustmann R. de Groot H. Iron-induced mitochondrial permeability transition in cultured hepatocytes. J Hepatol 2004; 40: 607-15.
[7]
Argyropoulou MI, Astrakas L. MRI evaluation of tissue iron burden in patients with beta-thalassaemia major. Pediatr Radiol 2007; 37: 1191-200.
[8]
Cappellini MD. Exjade(R) (deferasirox, ICL670) in the treatment of chronic iron overload associated with blood transfusion. Ther Clin Risk Manag 2007; 3: 291-9.
[9]
Galaris D, Pantopoulos K. Oxidative stress and iron homeostasis: Mechanistic and health aspects. Crit Rev Clin Lab Sci 2008; 45: 1-23.
[10]
Richardson DR. The therapeutic potential of iron chelators. Expert Opin Investig Drugs 1999; 8: 2141-58.
[11]
Al-Refaie FN, Wonke B, Hoffbrand AV, Wickens DG, Nortey P, Kontoghiorghes GJ. Efficacy and possible adverse effects of the oral iron chelator 1, 2- dimethyl-3-hydroxypyrid-4-one (L1) in thalassemia major. Blood 1992; 80: 593-9.
[12]
Nasir E, Ali SI. The flora of West Pakistan, An annotated catalogue of the vascular plants of West Pakistan and Kashmir. Fakhri Printing Press: Karachi 1972; p. 316.
[13]
Ahmad F, Ahmad K, Ahmad S. The studies on medicinal plants of Cholistan Desert, Pakistan. Lambert Academic Publishing: Germany 2011; p. 232.
[14]
Hayat MM, Uzair M, Chaudhary BA, et al. Phytochemical evaluation of Farsetia hamiltonii Royle from Cholistan desert. J Chem Soc Pak 2015; 37: 335-41.
[15]
Hayat MM, Sarwar S, Anjum S, et al. Anti-diabetic and spasmolytic potential of Farsetia hamiltonii Royle from Cholistan desert. J Ethnopharmacol 2014; 156: 347-52.
[16]
Hazra B, Biswas S, Mandal N. Antioxidant and free radical scavenging activity of Spondias pinnata. BMC Complement Altern Med 2008; 8: 63.
[17]
Das A, Chaudhuri D, Mandal N, Chatterjee A. Study of antioxidant and reactive oxygen species scavenging activity of the edible tuber of “greater yam”(Dioscorea alata L.) from north-east India. Asian J Pharm Clin Res 2012; 5: 74-84.
[18]
Chaudhuri D, Ghate NB, Panja S, Basu T, Shendge AK, Mandal N. Glycoside rich fraction from Spondias pinnata bark ameliorate iron overload induced oxidative stress and hepatic damage in Swiss albino mice. BMC Complement Altern Med 2016; 16: 262.
[19]
Lowry OH, Roesborough MJ, Farr AL, Randall RJ. Protein measurement with Folin-Phenol reagent. J Biol Chem 1951; 193: 265-75.
[20]
Barry M, Sherlock S. Measurement of liver iron concentration in needle-biopsy specimens. Lancet 1971; 297: 100-3.
[21]
Chaudhuri D, Ghate NB, Panja S, Mandal N. Role of phenolics from Spondias pinnata bark in amelioration of iron overload induced hepatic damage in Swiss albino mice. BMC Pharmacol Toxicol 2016; 17: 34.
[22]
Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 1984; 21: 130-2.
[23]
Bonaventura J, Schroeder WA, Fang S. Human erythrocyte catalase: An improved method of isolation and a re-evaluation of reported properties. Arch Biochem Biophys 1972; 150: 606-17.
[24]
Habig WH, Pabst MJ, Jakoby WB. Glutathione S transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974; 249: 7130-9.
[25]
Ellman GL. Tissue sulfhydryl group. Arch Biochem Biophys 1959; 82: 70-7.
[26]
Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978; 52: 302-10.
[27]
Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 1994; 233: 357-63.
[28]
Arezzini B, Lunghi B, Lungarella G, Gardi C. Iron overload enhances the development of experimental liver cirrhosis in mice. Int J Biochem Cell Biol 2003; 35: 486-95.
[29]
Hynes MJ, Coinceanainn M. Investigation of the release of iron from ferritin by naturally occurring antioxidants. J Inorg Biochem 2002; 90: 18-21.
[30]
Harborne JB, Baxter H. Phytochemical dictionary: A handbook of bioactive compounds from plants 4 John St. London: Taylor & Francis Ltd 1995.
[31]
Kokate CK, Purohit AP, Gokhale SB. Test book of Pharmacognosy. Pune: Nirali Prakashan 2003.
[32]
Arabshahi-Delouee S, Urooj A. Antioxidant properties of various solvent extracts of mulberry (Morus indica L.) leaves. Food Chem 2007; 102: 1233-40.
[33]
Bonkovsky HL. Iron and the liver. Am J Med Sci 1991; 301: 32-43.
[34]
Rothman RJ, Serroni A, Farber JL. Cellular pool of transient ferric iron, chelatable by deferoxamine and distinct from ferritin that is involved in oxidative cell injury. Mol Pharmacol 1992; 42: 703-10.
[35]
Aruoma OI, Halliwell B, Hoey BM, Butter J. The antioxidant action of N-acetylcysteine: Its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med 1989; 6: 593-7.
[36]
Kochevar EI, Redmond WR. Photosensitized production of singlet oxygen. Methods Enzymol 2000; 319: 20-8.
[37]
Huie RE, Padmaja S. The reaction of NO with superoxide. Free Radic Res 1993; 18: 195-9.
[38]
Crichton RR. Ferritin: Structure, synthesis and function. N Engl J Med 1971; 284: 1413-22.
[39]
Zuyderhoudt FM, Sindram JW, Marx JJ, Jörning GG, Van Gool J. The amount of ferritin and hemosiderin in the livers of patients with iron-loading disease. Hepatology 1983; 3: 232-5.
[40]
Reddy AC, Lokesh BR. Effect of curcumin and eugenol on iron-induced hepatic toxicities in rats. Toxicology 1996; 107: 39-45.
[41]
Wang H, Joseph JA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 1999; 27: 612-6.
[42]
Lledias F, Rangel P, Hansberg W. Oxidation of catalase by singlet oxygen. J Biol Chem 1998; 273: 10630.
[43]
Galleano M, Puntarulo S. Mild iron overload effect on rat liver nuclei. Toxicology 1994; 93: 125-34.
[44]
Bacon BR, Britton RS. The pathology of hepatic iron overload: a free radical mediated process? Hepatology 1990; 11: 127-37.
[45]
Ramm GA, Ruddell RG. Hepatotoxicity of iron overload: Mechanisms of iron-induced hepatic fibrogenesis. Semin Liver Dis 2005; 25: 433-49.
[46]
Arthur MJ. Iron overload and liver fibrosis. J Gastroenterol Hepatol 1996; 11: 1124-9.
[47]
Özgüner M, Sayın N. Histological changes in rat liver after chronic iron-sorbitol overload. J Ankara Med School 2002; 24: 49-54.
[48]
Brien RT. Ascorbic acid enhancement of desferrioxamine induced urinary iron excretion in thalassemia major. Ann N Y Acad Sci 1974; 232: 221-5.
[49]
Rice-Evans CA, Miller NJ, Bolwell PG, Bramley PM, Pridham JB. The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radic Res 1995; 22: 375-83.
[50]
Atanassova M, Georgieva S, Ivancheva K. Total phenolic and total flavonoid contents, antioxidant capacity and biological contaminants in medicinal herbs. J Chem Technol Metall 2011; 46: 81-8.
[51]
Cai Y, Luo Q, Sun M, Corke H. Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci 2004; 74: 2157-84.
[52]
Gülcįn I, Huyut Z, Elmastas M, Aboul-Enein HY. Radical scavenging and antioxidant activity of tannic acid. Arab J Chem 2010; 3: 43-53.
[53]
Hassan S, Rizk MZ, El-Sharkawi F, Badary O, Kadry MO. Hepatoprotective and antioxidant activity of phytic acid and/or catechin against carbon tetrachloride-induced hepatotoxicity in rats. Toxicol Lett 2009; 189: S265-66.
[54]
Adikwu E, Deo O. Hepatoprotective effect of Vitamin C (Ascorbic Acid). Pharmacol Pharm 2013; 4: 84-92.


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Article Details

VOLUME: 16
ISSUE: 2
Year: 2019
Page: [210 - 222]
Pages: 13
DOI: 10.2174/1570163815666180418150123
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