Supplementation of Psidium Guajava Leaves Powder Prevents Hepatotoxicity and Inflammation in Carbon Tetrachloride (CCl4)-Administered Rats

Author(s): Nitol Debnath, Farzana B. Rafique, Nasrin Akhter, Anayt Ulla, Tahmina Yasmin, Md Nurul Islam*, Md A. Alam*

Journal Name: Current Bioactive Compounds

Volume 17 , Issue 4 , 2021


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Aims and Objective: Various studies revealed the antioxidant and anti-inflammatory properties of Psidium guajava leaves. This present study reported the anti-inflammatory and protective effects of Psidium guajava leaves on Carbon tetrachloride (CCl4) induced rat liver.

Methods: In this study, Long Evans female rats (150-180 g) were divided into four groups. CCl4 in olive oil was given orally by gavage at a dose of 1 mL/kg and Psidium guajava leave powder was provided as 2.5% w/w of food. Liver marker enzyme activity was monitored by evaluating the alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatases (ALP) in plasma. The plasma and liver tissue concentrations of thiobarbituric acid reactive substances (TBARS), Nitric Oxide (NO), advanced protein oxidation product (APOP), glutathione (GSH, in reduced form) and activity of catalase were measured as an oxidative stress marker.

Results: The results of this study suggested the serum transferase activities were increased in CCl4 administered rat, which was normalized by Psidium guajava leaves supplementation. Moreover, oxidative stress markers were significantly reduced and antioxidant enzyme activity was significantly improved by Psidium guajava leaves supplementation in CCl4 administered rat. Hematoxylin and Eosin and Picrosirius Red staining of liver section revealed reduced inflammatory cell infiltration and fibrosis, respectively by Psidium guajava leaves supplementation in CCl4 administered rats.

Conclusion: In conclusion, Psidium guajava leaves may prevent liver damage and inflammation in CCl4-administered rats, which indicated strong antioxidant capacity. Thus, Psidium guajava leaves could be a source of natural antioxidants. Further study is required for using Psidium guajava leaves in the clinical case of liver dysfunction.

Keywords: carbon tetrachloride, fibrosis, malondialdehyde, Psidium guajava, reactive oxygen species, inflammatory hepatitis.

[1]
Hosseini, V.; Maroufi, N.F.; Saghati, S.; Asadi, N.; Darabi, M.; Ahmad, S.N.S.; Hosseinkhani, H.; Rahbarghazi, R. Current progress in hepatic tissue regeneration by tissue engineering. J. Transl. Med., 2019, 17(1), 383.
[http://dx.doi.org/10.1186/s12967-019-02137-6] [PMID: 31752920]
[2]
Veith, A.; Moorthy, B. Role of cytochrome p450 in the generation and metabolism of reactive oxygen species. Curr. Opin. Toxicol., 2018, 7, 44-51.
[http://dx.doi.org/10.1016/j.cotox.2017.10.003] [PMID: 29527583]
[3]
Li, S.; Hong, M.; Tan, H-Y.; Wang, N.; Feng, Y. Insights into the role and interdependence of oxidative stress and inflammation in liver diseases. Oxid. Med. Cell. Longev., 2016, 2016, 4234061.
[http://dx.doi.org/10.1155/2016/4234061] [PMID: 28070230]
[4]
He, L.; He, T.; Farrar, S.; Ji, L.; Liu, T.; Ma, X. Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species. Cell. Physiol. Biochem., 2017, 44(2), 532-553.
[http://dx.doi.org/10.1159/000485089] [PMID: 29145191]
[5]
Di Meo, S.; Reed, T.T.; Venditti, P.; Victor, V.M. Role of ROS and RNS sources in physiological and pathological conditions. Oxid. Med. Cell. Longev., 2016, 2016, 1245049.
[http://dx.doi.org/10.1155/2016/1245049] [PMID: 27478531]
[6]
Li, S.; Tan, H-Y.; Wang, N.; Zhang, Z-J.; Lao, L.; Wong, C-W.; Feng, Y. The role of oxidative stress and antioxidants in liver diseases. Int. J. Mol. Sci., 2015, 16(11), 26087-26124.
[http://dx.doi.org/10.3390/ijms161125942] [PMID: 26540040]
[7]
Scholten, D.; Trebicka, J.; Liedtke, C.; Weiskirchen, R. The carbon tetrachloride model in mice. Lab. Anim., 2015, 49(1)(Suppl.), 4-11.
[http://dx.doi.org/10.1177/0023677215571192] [PMID: 25835733]
[8]
Patlevič, P.; Vašková, J.; Švorc, P., Jr; Vaško, L.; Švorc, P. Reactive oxygen species and antioxidant defense in human gastrointestinal diseases. Integr. Med. Res., 2016, 5(4), 250-258.
[http://dx.doi.org/10.1016/j.imr.2016.07.004] [PMID: 28462126]
[9]
Sahreen, S.; Khan, M.R.; Khan, R.A. Hepatoprotective effects of methanol extract of Carissa opaca leaves on CCl4-induced damage in rat. BMC Complement. Altern. Med., 2011, 11(1), 48.
[http://dx.doi.org/10.1186/1472-6882-11-48] [PMID: 21699742]
[10]
Kegel, V.; Pfeiffer, E.; Burkhardt, B.; Liu, J.L.; Zeilinger, K.; Nüssler, A.K.; Seehofer, D.; Damm, G. Subtoxic concentrations of hepatotoxic drugs lead to Kupffer cell activation in a human in vitro liver model: An approach to study DILI. Mediators Inflamm., 2015, 2015, 640631.
[http://dx.doi.org/10.1155/2015/640631] [PMID: 26491234]
[11]
Jang, M.; Jeong, S.W.; Cho, S.K.; Ahn, K.S.; Lee, J.H.; Yang, D.C.; Kim, J.C. Anti-inflammatory effects of an ethanolic extract of guava (Psidium guajava L.) leaves in vitro and in vivo. J. Med. Food, 2014, 17(6), 678-685.
[http://dx.doi.org/10.1089/jmf.2013.2936] [PMID: 24738717]
[12]
Gitiara, A.; Tokhanbigli, S.; Mazhari, S.; Baghaei, K.; Hatami, B.; Hashemi, S.M.; Asadi Rad, A.; Moradi, A.; Nasiri, M.; Zarrabi Ahrabi, N.; Zali, M.R. Development of experimental fibrotic liver diseases animal model by Carbon Tetracholoride. Gastroenterol. Hepatol. Bed Bench, 2017, 10(Suppl. 1), S122-S128.
[PMID: 29511482]
[13]
Brol, M.J.; Rösch, F.; Schierwagen, R.; Magdaleno, F.; Uschner, F.E.; Manekeller, S.; Queck, A.; Schwarzkopf, K.; Odenthal, M.; Drebber, U.; Thiele, M.; Lingohr, P.; Plamper, A.; Kristiansen, G.; Lotersztajn, S.; Krag, A.; Klein, S.; Rheinwalt, K.P.; Trebicka, J. Combination of CCl4 with alcoholic and metabolic injuries mimics human liver fibrosis. Am. J. Physiol. Gastrointest. Liver Physiol., 2019, 317(2), G182-G194.
[http://dx.doi.org/10.1152/ajpgi.00361.2018] [PMID: 31188634]
[14]
Yanguas, S.C.; Cogliati, B.; Willebrords, J.; Maes, M.; Colle, I.; van den Bossche, B.; de Oliveira, C.P.M.S.; Andraus, W.; Alves, V.A.F.; Leclercq, I.; Vinken, M. Experimental models of liver fibrosis. Arch. Toxicol., 2016, 90(5), 1025-1048.
[http://dx.doi.org/10.1007/s00204-015-1543-4] [PMID: 26047667]
[15]
Latief, U.; Ahmad, R. Herbal remedies for liver fibrosis: A review on the mode of action of fifty herbs. J. Tradit. Complement. Med., 2017, 8(3), 352-360.
[http://dx.doi.org/10.1016/j.jtcme.2017.07.002] [PMID: 29992106]
[16]
Islam, M.A.; Al Mamun, M.A.; Faruk, M.; Ul Islam, M.T.; Rahman, M.M.; Alam, M.N.; Rahman, A.F.M.T.; Reza, H.M.; Alam, M.A. Astaxanthin ameliorates hepatic damage and oxidative stress in carbon tetrachloride-administered rats. Pharmacognosy Res., 2017, 9(Suppl. 1), S84-S91.
[http://dx.doi.org/10.4103/pr.pr_26_17] [PMID: 29333048]
[17]
Forni, C.; Facchiano, F.; Bartoli, M.; Pieretti, S.; Facchiano, A.; D’Arcangelo, D.; Norelli, S.; Valle, G.; Nisini, R.; Beninati, S.; Tabolacci, C.; Jadeja, R.N. Beneficial role of phytochemicals on oxidative stress and age-related diseases. BioMed Res. Int., 2019, 2019, 8748253.
[http://dx.doi.org/10.1155/2019/8748253] [PMID: 31080832]
[18]
Ravi, K.; Divyashree, P. Psidium guajava: A review on its potential as an adjunct in treating periodontal disease. Pharmacogn. Rev., 2014, 8(16), 96-100.
[http://dx.doi.org/10.4103/0973-7847.134233] [PMID: 25125881]
[19]
Díaz-de-Cerio, E.; Verardo, V.; Gómez-Caravaca, A.M.; Fernández-Gutiérrez, A.; Segura-Carretero, A. Health effects of Psidium guajava L. leaves: An overview of the last decade. Int. J. Mol. Sci., 2017, 18(4), 897.
[http://dx.doi.org/10.3390/ijms18040897] [PMID: 28441777]
[20]
Mamun, M.A.A.; Faruk, M.; Rahman, M.M.; Nahar, K.; Kabir, F.; Alam, M.A.; Subhan, N. High carbohydrate high fat diet induced hepatic steatosis and dyslipidemia were ameliorated by Psidium guajava leaf oowder supplementation in rats. Evid. Based Complement. Alternat. Med., 2019, 2019, 1897237.
[http://dx.doi.org/10.1155/2019/1897237] [PMID: 30854003]
[21]
Rahman, M.M.; Zaman, S.; Mamun, F.; Gias, Z.T.; Alam, M.N.; Ulla, A. Phenolic content analysis in Psidium guajava leaves powder by HPLC-DAD system and in vivo renoprotective and antioxidant activities in fludrocortisone acetate-induced rats. J. Food Biochem., 2018, 42(6), e12687.
[http://dx.doi.org/10.1111/jfbc.12687]
[22]
Sambo, N.; Garba, S.H.; Timothy, H. Effect of the aqueous extract of Psidium guajava on erythromycin-induced liver damage in rats. Niger. J. Physiol. Sci., 2009, 24(2), 171-176.
[PMID: 20234760]
[23]
Mada, S.; Mohammed, A.; Garba, A.; Mohammed, H.; Garba, I. Modulatory effect of aqueous stem bark extract of Psidium guajava Linn against CCl4 induced liver damage in rats. Am J Biochem Mol Biol., 2013, 3(2), 215-227.
[http://dx.doi.org/10.3923/ajbmb.2013.215.227]
[24]
Niehaus, W.G., Jr; Samuelsson, B. Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur. J. Biochem., 1968, 6(1), 126-130.
[http://dx.doi.org/10.1111/j.1432-1033.1968.tb00428.x] [PMID: 4387188]
[25]
Witko-Sarsat, V.; Friedlander, M.; Capeillère-Blandin, C.; Nguyen-Khoa, T.; Nguyen, A.T.; Zingraff, J.; Jungers, P.; Descamps-Latscha, B. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int., 1996, 49(5), 1304-1313.
[http://dx.doi.org/10.1038/ki.1996.186] [PMID: 8731095]
[26]
Jollow, D.J.; Mitchell, J.R.; Zampaglione, N.; Gillette, J.R. Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology, 1974, 11(3), 151-169.
[http://dx.doi.org/10.1159/000136485] [PMID: 4831804]
[27]
Khan, R.A. Protective effects of Sonchus asper (L.) Hill, (Asteraceae) against CCl(4-)induced oxidative stress in the thyroid tissue of rats. BMC Complement. Altern. Med., 2012, 12(1), 181.
[http://dx.doi.org/10.1186/1472-6882-12-181] [PMID: 23043630]
[28]
Fortea, J.I.; Fernández-Mena, C.; Puerto, M.; Ripoll, C.; Almagro, J.; Bañares, J.; Bellón, J.M.; Bañares, R.; Vaquero, J. Comparison of two protocols of carbon tetrachloride-induced cirrhosis in rats – improving yield and reproducibility. Sci. Rep., 2018, 8(1), 9163.
[http://dx.doi.org/10.1038/s41598-018-27427-9] [PMID: 29907790]
[29]
Ito, F.; Sono, Y.; Ito, T. Measurement and clinical significance of lipid peroxidation as a biomarker of oxidative stress: Oxidative stress in diabetes, atherosclerosis, and chronic inflammation. Antioxidants, 2019, 8(3), 72.
[http://dx.doi.org/10.3390/antiox8030072] [PMID: 30934586]
[30]
Dutta, S.; Chakraborty, A.K.; Dey, P.; Kar, P.; Guha, P.; Sen, S.; Kumar, A.; Sen, A.; Chaudhuri, T.K. Amelioration of CCl4 induced liver injury in swiss albino mice by antioxidant rich leaf extract of Croton bonplandianus Baill. PLoS One, 2018, 13(4), e0196411.
[http://dx.doi.org/10.1371/journal.pone.0196411] [PMID: 29709010]
[31]
Iwakiri, Y. Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase. Clin. Mol. Hepatol., 2015, 21(4), 319-325.
[http://dx.doi.org/10.3350/cmh.2015.21.4.319] [PMID: 26770919]
[32]
Osman, M.; Ahmed, M.; Mahfouz, S.; Elaby, S. Biochemical studies on the hepatoprotective effects of pomegranate and guava ethanol extracts. New York Sci J., 2011, 4(3), 27-41.
[33]
Koyama, Y.; Brenner, D.A. Liver inflammation and fibrosis. J. Clin. Invest., 2017, 127(1), 55-64.
[http://dx.doi.org/10.1172/JCI88881] [PMID: 28045404]
[34]
Sato, K.; Hall, C.; Glaser, S.; Francis, H.; Meng, F.; Alpini, G. Pathogenesis of Kupffer cells in cholestatic liver injury. Am. J. Pathol., 2016, 186(9), 2238-2247.
[http://dx.doi.org/10.1016/j.ajpath.2016.06.003] [PMID: 27452297]
[35]
Mehta, K.J.; Farnaud, S.J.; Sharp, P.A. Iron and liver fibrosis: Mechanistic and clinical aspects. World J. Gastroenterol., 2019, 25(5), 521-538.
[http://dx.doi.org/10.3748/wjg.v25.i5.521] [PMID: 30774269]
[36]
Mello, T.; Zanieri, F.; Ceni, E.; Galli, A. Oxidative stress in the healthy and wounded hepatocyte: A cellular organelles perspective. Oxid. Med. Cell. Longev., 2016, 2016, 8327410.
[http://dx.doi.org/10.1155/2016/8327410] [PMID: 26788252]
[37]
Milic, S.; Mikolasevic, I.; Orlic, L.; Devcic, E.; Starcevic-Cizmarevic, N.; Stimac, D.; Kapovic, M.; Ristic, S. The Role of iron and iron overload in chronic liver disease. Med. Sci. Monit., 2016, 22, 2144-2151.
[http://dx.doi.org/10.12659/MSM.896494] [PMID: 27332079]
[38]
Lee, C-C.; Shen, S-R.; Lai, Y-J.; Wu, S-C. Rutin and quercetin, bioactive compounds from tartary buckwheat, prevent liver inflammatory injury. Food Funct., 2013, 4(5), 794-802.
[http://dx.doi.org/10.1039/c3fo30389f] [PMID: 23584161]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 4
Year: 2021
Published on: 15 July, 2020
Page: [356 - 365]
Pages: 10
DOI: 10.2174/1573407216999200715162928
Price: $65

Article Metrics

PDF: 42
HTML: 1