Pharmacological impact of Agaricus bisporus extract in carbon tetrachloride-induced hepatotoxicity in rats


  • Manar Rizk Benha University
  • Deena El-Deberky Benha University
  • Faten El-Sayed Benha University
  • Aziza Amin Benha University
  • Abubakr El-Mahmoudy Benha University



Agaricus bisporus, Mushroom, Liver Injury, CCl4, Antioxidant, Phytomedicine.


Drug-induced hepatotoxicity is a frequent cause of liver injury worldwide. The present study was designed to evaluate the possible hepato-protective potential Agaricus bisporus extract (ABE; a type of mushrooms) in albino rats using Carbon tetrachloride (CCl4)-model of liver injury. Forty-two albino rats were utilized in this experiment arranged randomly in seven groups, six rats each, of different treatments. He-patic injury model was induced by administration of CCl4 (25% in corn oil) at a dose of 2.5 ml/kg, interperitoneally, twice weekly for 8 weeks (+ve control); test group rats received ABE at escalating doses of 200 or 400 mg/kg, orally, daily for 8 weeks with exposure to CCl4; standard group rats received Silymarin at dose of 100 mg/kg, orally, daily for 8 weeks along with CCl4; further 2 groups of rats received only ABE at the same dose levels; while rats of -ve control group received only the vehicles of the used drugs. Blood and liver tissue sam-ples were picked out at the end of the experimental course for different assays. Biochemical analysis revealed that ABE exhibited dose-dependent hepatoprotection indicated by almost normalized biomarkers, including, enzymatic liver function parameters, namely, AST, ALT, GGT & ALP with potential % of 93.1, 58.2, 65.2, 68.9, respectively, after ABE large dose when standardized by Silymarin; non-enzymatic parameters, namely, total protein, albumin, globulins, total bilirubin, conjugated bilirubin, unconjugated bilirubin, TAGs, Cholesterol, HDL, LDL & VLDL with potential % of 59.3, 54.5, 57.3, 81.8, 81.0, 80.0, 75.5, 90.4, 80.8, 84.5 & 78.7, respectively, after ABE large dose when standardized by Silymarin. The mechanism of the obtained hepatoprotection of ABE may be based on impeding the oxidative stress mediated by the used hepatotoxin, indicated by reduced MDA (37.9 % of Silymarin), and restored SOD, Catalase & GPx in liver homogenate with potentials of 94.9, 63.0 & 88.4 % of Silymarin, respectively. Pathological findings, both macroscopic and microscopic, were supportive to the biochemical findings, where the pathological lesions caused by CCl4 as fatty degeneration of hepatocytes with vacuolated cytoplasm, proliferated fibrous connective tissue with eosinophilic edematous fluid cells plus focal and diffuse necrotic areas and hyperplastic biliary epithelium, were ameliorated dose-dependently when ABE was administered together with CCl4. Data of the present study may suggest ABE as a good natural source for promising hepatoprotective and antioxidative remedies.


[1] Acharya K, Chatterjee S, Biswas G, Chatterjee A, Saha GK (2012). Hepatoprotective effect of a wild edible mushroom on carbon tetrachloride-induced hepatotoxicity in mice. International Journal of Pharmacy and Pharmaceutical Sciences 4, 285-288.

[2] Aebi H (1984). Catalase in vitro. Methods Enzymol 105, 121-126.

[3] Al-Dbass AM, Al-Daihan SK, Bhat RS (2012). Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats. Saudi journal of biological sciences 19, 303-309.

[4] Ali DK, Al-Bahrani R, Majeed SA (2018). The Protective Role of Agaricus bisporus in Experimental Liver Injury in Mice. IOSR Journal of Pharmacy and Biological Sciences 13, 23-28.

[5] Bancroft JD, Gamble M (2008). Theory and practice of histological techniques: Elsevier health sciences.

[6] Bas CF, Marks R (1991). The layered perceptron versus the Neyman-Pearson optimal detection. In: Proc. Int. Joint Conf. Neural Networks. p 1486-1489.

[7] Bastos GA, Soares ACM, Vieira TM, de Souza Cândido RC, Morais-Costa F, de Oliveira Vasconcelos V, Oliveira NJF, Duarte ER (2016). Blood parameters of sheep with high infection of Haemonchus contortus and treated with “mushroom of the sun†(Agaricus blazei). Semina: Ciências Agrárias 37, 807-818.

[8] Belfield A, Goldberg D (1971). Revised assay for serum phenyl phosphatase activity using 4-amino-antipyrine. Enzyme 12, 561-573.

[9] Bell LN, Chalasani N (2009). Epidemiology of idiosyncratic drug-induced liver injury. In: Seminars in liver disease: © Thieme Medical Publishers. p 337-347.

[10] Bhushan A, Kulshreshtha M (2018). The medicinal Mushroom Agaricus bisporus: Review of phytopharmacology and potential role in the treatment of various diseases. Journal of Nature and Science of Medicine 1, 4.

[11] Bissell DM, Gores GJ, Laskin DL, Hoofnagle JH (2001). Drugâ€induced liver injury: mechanisms and test systems. Hepatology 33, 1009-1013.

[12] Busher JT (1990). Serum albumin and globulin. Clinical methods: The history, physical, and laboratory examinations 3, 497-499.

[13] Chang J-B, Wu M-F, Yang Y-Y, Leu S-J, Chen Y-L, Yu C-S, Yu C-C, Chang S-J, Lu H-F, Chung J-G (2011). Carbon tetrachloride-induced hepatotoxicity and its amelioration by Agaricus blazei Murrill extract in a mouse model. in vivo 25, 971-976.

[14] Del Maestro R, McDonald W (1985). Oxidative enzymes in tissue homogenates: Boca Raton, FL, CRC Press.

[15] Doumas BT, Watson WA, Biggs HG (1971). Albumin standards and the measurement of serum albumin with bromcresol green. Clinica chimica acta 31, 87-96.

[16] El-Mahmoudy AM, Abdel-Fattah FA, Abd El-Mageid AD, Gheith IM (2014). Effect of the growth promotant mannan-oligosaccharide on the lipogram and organ function profile in hyperlipidemic albino rats. Am. J. Phytomed. Clin. Ther 2, 334-347.

[17] Fassati P, Prencipe L (1982). Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 28, 2077-2080.

[18] Feng Y, Zhang J, Wen C, Dzah CS, Juliet IC, Duan Y, Zhang H (2020). Recent advances in Agaricus bisporus polysaccharides: Extraction, purification, physicochemical characterization and bioactivities. Process Biochemistry.

[19] Gheith I, El-Mahmoudy A (2018). Laboratory evidence for the hematopoietic potential of Beta vulgaris leaf and stalk extract in a phenylhydrazine model of anemia. Brazilian Journal of Medical and Biological Research 51.

[20] Gornall A (1949). Bardawill CJ, and David MM. Determination of serum proteins by means of the biuret reaction. J Biol Chem 177, 751-766.

[21] Harborn J (1973). Photochemical methods. Hasted Presses. In: John Wiley and Sons, New York.

[22] Hardin Jr B (1954). Carbon Tetrachloride Poisoning-a Review. Industrial Medicine and Surgery, 93-105.

[23] Hong Y-C (2019). Method of Ending Disease and the Future Medical System. The Changing Era of Diseases, 109.

[24] Jeong SC, Jeong YT, Yang BK, Islam R, Koyyalamudi SR, Pang G, Cho KY, Song CH (2010). White button mushroom (Agaricus bisporus) lowers blood glucose and cholesterol levels in diabetic and hypercholesterolemic rats. Nutrition research 30, 49-56.

[25] Junior DV, de Oliveira NJF, Duarte ER, Bastos GA, Soares ACM, Cassali GD, Soto-Blanco B, Melo MM (2016). Serum hepatic biochemistry and electrophoretic protein profile of healthy and Ehrlich tumor-bearing mice treated with extracts of Agaricus blazei Murill. Semina: Ciências Agrárias 37, 763-772.

[26] Kanaya N, Kubo M, Liu Z, Chu P, Wang C, Yuan Y-C, Chen S (2011). Protective effects of white button mushroom (Agaricus bisporus) against hepatic steatosis in ovariectomized mice as a model of postmenopausal women. PLoS One 6, e26654.

[27] Karaman M, Mimica-Dukic N, Knezevic P, Svircev Z, Matavuly M (2009). Antibacterial properties of selected lignicolous mushrooms and fungi from northern Serbia. International Journal of Medicinal Mushrooms 11.

[28] Khan M, Tania M, Zhang D, Chen H (2010). Cordyceps mushroom: a potent anticancer nutraceutical. The Open Nutraceutical Journal 3, 179.

[29] Khudhair DHA (2018). Effect of aqueous extract of Agaricus bispporus on lipid profile of female albino mice treated with peroxide. Iraqi Journal of Science, 2168-2172.

[30] Koumbi L (2017). Dietary factors can protect against liver cancer development. World journal of hepatology 9, 119.

[31] Krinke GJ (2000). The laboratory rat: Elsevier.

[32] Kshirsagar A, Ingawale D, Ashok P, Vyawahare N (2009). Silymarin: A comprehensive review. Pharmacognosy Reviews 3, 126.

[33] Liu Y, Zheng D, Su L, Wang Q, Li Y (2018). Protective effect of polysaccharide from Agaricus bisporus in Tibet area of China against tetrachloride-induced acute liver injury in mice. International journal of biological macromolecules 118, 1488-1493.

[34] Lopes-Virella MF, Stone P, Ellis S, Colwell JA (1977). Cholesterol determination in high-density lipoproteins separated by three different methods. Clinical chemistry 23, 882-884.

[35] Nieminen P, Kärjä V, Mustonen A-M (2009). Myo-and hepatotoxic effects of cultivated mushrooms in mice. Food and Chemical Toxicology 47, 70-74.

[36] Nishikimi M, Roa N, Yogi K (1972). Improved method for the determination of red blood cell superoxide activity Biochem. Biop. Res. Common 46, 849-854.

[37] Ohkawa H, Ohishi N, Yagi K (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry 95, 351-358.

[38] Omar A, Abou-Alfa GK, Khairy A, Omar H (2013). Risk factors for developing hepatocellular carcinoma in Egypt. Chinese clinical oncology 2.

[39] Paglia DE, Valentine WN (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. The Journal of laboratory and clinical medicine 70, 158-169.

[40] Pujar S, Kashinakunti S, Gurupadappa K, Manjula R (2011). Serum MDA, antioxidant vitamins and erythrocytic antioxidant enzymes in chronic alcoholic liver disease–a case control study. Al Ameen J Med Sci 4, 315-322.

[41] Reitman S, Frankel S (1957). Glutamic–pyruvate transaminase assay by colorimetric method. Am. J. Clin. Path 28, 56.

[42] Richmond W (1973). Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clinical chemistry 19, 1350-1356.

[43] Russmann S, Kullak-Ublick GA, Grattagliano I (2009). Current concepts of mechanisms in drug-induced hepatotoxicity. Current medicinal chemistry 16, 3041-3053.

[44] Ruthes AC, Smiderle FR, Iacomini M (2015). D-Glucans from edible mushrooms: A review on the extraction, purification and chemical characterization approaches. Carbohydrate polymers 117, 753-761.

[45] Sacchetti L, Castaldo G, Fortunato G, Salvatore F (1988). Improved procedure for measuring gamma-glutamyltransferase isoenzymes in serum. Clinical chemistry 34, 419-422.

[46] Shekhany KA, Al-Jibouri MH, Faraj MK (2012). The protective effect of white button mushroom (Agaricus bisporus) extract against zearalenone toxicity in albino mice. In: Proceedings of the 4th Kurdistan Conference on Biological Sciences. University of Duhok. p 10.

[47] Singhal KG, Gupta GD (2012). Hepatoprotective and antioxidant activity of methanolic extract of flowers of Nerium oleander against CCl4–induced liver injury in rats. Asian Pacific Journal of Tropical Medicine 5, 677-685.

[48] Soares AA, de Oliveira AL, Sá-Nakanishi AB, Comar JF, Rampazzo AP, Vicentini FA, Natali MR, Gomes da Costa SM, Bracht A, Peralta RM (2013). Effects of an Agaricus blazei aqueous extract pretreatment on paracetamol-induced brain and liver injury in rats. BioMed research international 2013.

[49] Teplyakova TV, Psurtseva NV, Kosogova TA, Mazurkova NA, Khanin VA, Vlasenko VA (2012). Antiviral activity of polyporoid mushrooms (higher Basidiomycetes) from Altai Mountains (Russia). International Journal of Medicinal Mushrooms 14.

[50] Vargas-Mendoza N, Madrigal-Santillán E, Morales-González Ã, Esquivel-Soto J, Esquivel-Chirino C, y González-Rubio MG-L, Gayosso-de-Lucio JA, Morales-González JA (2014). Hepatoprotective effect of silymarin. World journal of hepatology 6, 144.

[51] Walter M, Gerade H (1970). A colorimetric method for determination bilirubin in serum and plasma. Micro Chem J 15, 231-236.

[52] Wang H, Ng T (2006). Ganodermin, an antifungal protein from fruiting bodies of the medicinal mushroom Ganoderma lucidum. Peptides 27, 27-30.

[53] Wieland H, Seidel D (1983). A simple specific method for precipitation of low-density lipoproteins. Journal of Lipid Research 24, 904-909.

[54] Wilson PW, Abbott RD, Garrison RJ, Castelli WP (1981). Estimation of very-low-density lipoprotein cholesterol from data on triglyceride concentration in plasma. Clinical chemistry 27, 2008-2010.


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