Abstract
Pleurotus tuber regium, a wild edible mushroom can reduce free radical-mediated injury and oxidative stress induced by carbon tetrachloride (CCl4) via improvement of antioxidant capacity. This work evaluates the protective effects of this mushroom against the metabolic and hematological toxicity induced by CCl4. Sixty male Sprague Dawley rats were divided into six groups (n = 10). Group I received olive oil (3 mL/kg) i.p. twice weekly for 13 weeks, while maintaining free access to food and water ad libitum (negative control). Group II received 3 mL/kg (30% CCl4 in olive oil) injected i.p. twice weekly, while Groups III, IV, and V received 100, 200, and 500 mg wild edible P. tuber regium (33.3% in feed) daily in addition to 3 mL/kg CCl4 in olive oil injected twice weekly i.p. Group VI received olive oil (3 mL/kg) i.p. twice weekly for 13 weeks in addition to 500 mg P. tuber regium (33.3% in feed) daily. The body weight (b.w.), feed intake (FI), and water intake (WI) were obtained weekly, while the hematological indices and oxidative stress parameters were carried out shortly after necropsy on days 30, 60, and 90. Treatment with CCl4 significantly (p < 0.05) decreased the b.w., FI and WI, feed efficiency, ascorbic acid, α-tocopherol, and antioxidant enzymes, superoxide dismutase, catalase, total glutathione, and peroxidase, while increasing the oxidative stress as measured by malondialdehyde in CCl4 only group when compared with control. Supplementation of feed with P. tuber regium reversed the effects of CCl4. Pleurotus tuber regium ameliorated the CCl4-induced metabolic and hematotoxicity by improving the antioxidant capacity.
Research funding: The authors received no specific funding for this work.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Ethical approval: All the experimental procedures were performed according to the committee for the purpose of control and supervision of experiments on animals, norms and approved by the University of Port Harcourt Animal Ethical Committee with an approval number UNIPORT/PHARM/0133.
References
[1] Benson JM, Tibbetts BM, Thrall KD, Springer DL. Uptake, tissue distribution, and fate of inhaled carbon tetrachloride: comparison of rat, mouse, and hamster. Inhalation Toxicol 2001;13:207–17.10.1080/08958370150502449Search in Google Scholar PubMed
[2] Sanzgiri UY, Srivatsan V, Muralidhara S, Dallas CE, Bruckner JV. Uptake, distribution, and elimination of carbon tetrachloride in rat tissues following inhalation and ingestion exposures. Toxicol Appl Pharmacol 1997;143:120–9.10.1006/taap.1996.8079Search in Google Scholar PubMed
[3] Li X, Zhang F, Wang D, Li Z, Qin X, Du G. NMR-based metabonomic and quantitative real-time PCR in the profiling of metabolic changes in carbon tetrachloride-induced rat liver injury. J Pharmaceut Biomed Anal 2014;89:42–9.10.1016/j.jpba.2013.10.023Search in Google Scholar PubMed
[4] Li XX, Zheng QC, Wang Y, Zhang HX. Theoretical insights into the reductive metabolism of CCl4 by cytochrome P450 enzymes and the CCl4-dependent suicidal inactivation of P450. Dalton Trans 2014;43:14833–40.10.1039/C4DT02065KSearch in Google Scholar PubMed
[5] Essawy AE, Hamed SS, Abdel MA, Abou GA, Alzergy AA. Role of black seeds (Nigella sativa) in ameliorating carbon tetrachloride induced haematotoxicity in Swiss albino mice. J Med Plants Res 2010;4:1977–86.10.5897/JMPR10.504Search in Google Scholar
[6] Famurewa AC, Kanu SC, Ogugua VN, Nweke ML. Protective effect of pretreatment of rats with calyx extract of hibiscus sabdariffa against carbon tetrachloride-induced hematotoxicity. J Biol Sci 2015;15:138–43.10.3923/jbs.2015.138.143Search in Google Scholar
[7] Fujita K. A study on erythrocyte-membrane osmotic resistance and periodontal changes in rats treated with carbon tetrachloride. Shikwa Gakuho 1990;90:727–43.Search in Google Scholar
[8] Ismail A, Essawy M, Salem A. Protective effect of grape seed oil against CCl4 induced oxidative stress in rat brain. J Agric Chem Biotechnol Mansoura Univ 2014;5:287.10.21608/jacb.2014.50047Search in Google Scholar
[9] Ismail RS, El-Megeid AA, Abdel-Moemin AR. Carbon tetrachloride-induced liver disease in rats: the potential effect of supplement oils with vitamins E and C on the nutritional status. Ger Med Sci 2009;7:5.Search in Google Scholar
[10] Kataoka T, Nishiyama Y, Yamato K, Teraoka J, Morii Y, Sakoda, et al. Comparative study on the inhibitory effects of antioxidant vitamins and radon on carbon tetrachloride-induced hepatopathy. J Radiat Res 2012;53:830–9.10.1093/jrr/rrs057Search in Google Scholar PubMed PubMed Central
[11] Li CC, Hsiang CY, Wu SL, Ho TY. Identification of novel mechanisms of silymarin on the carbon tetrachloride-induced liver fibrosis in mice by nuclear factor-kappa B bioluminescent imaging-guided transcriptomic analysis. Food Chem Toxicol 2012;50:1568–75.10.1016/j.fct.2012.02.025Search in Google Scholar PubMed
[12] Okolo KO, Orisakwe OE, Siminialayi IM. Nephroprotective and antioxidant effects of king tuber oyster medicinal mushroom, Pleurotus tuber-regium (Agaricomycetes), on carbon tetrachloride-induced nephrotoxicity in male Sprague Dawley Rats. Int J Med Mushrooms 2018;20:419–29.10.1615/IntJMedMushrooms.2018026044Search in Google Scholar PubMed
[13] Akindahunsi A, Oyetayo F. Nutrient and antinutrient distribution of edible mushroom, Pleurotus tuber-regium (fries) singer. LWT-Food Sci Technol 2006;39:548–53.10.1016/j.lwt.2005.04.005Search in Google Scholar
[14] Ifeoma I, Ikechukwu A, Princess C, Henry I. Phytochemical composition of Pleurotus tuber regium and effect of its dietary incorporation on body/organ weights and serum triacylglycerols in albino mice. J Med Plants Res 2009;3:939–43.Search in Google Scholar
[15] Lull C, Wichers HJ, Savelkoul HF. Antiinflammatory and immunomodulating properties of fungal metabolites. Mediators Inflamm 2005;2: 63– 80.10.1155/MI.2005.63Search in Google Scholar
[16] Okolo KO, Orisakwe OE, Siminialayi IM. Pleurotus tuber-regium mushrooms in the diet of rats ameliorates reproductive and testicular injury caused by carbon tetrachloride. Clin Phytosci 2017;3:14.10.1186/s40816-017-0051-xSearch in Google Scholar
[17] Bailey C, Turner SL, Jakeman K, Hayes W. Effect of Coprinus comatus on plasma glucose concentrations in mice. Planta Med 1984;50:525–6.10.1055/s-2007-969791Search in Google Scholar
[18] Hoffman WP, Ness DK, Van Lier RB. Analysis of rodent growth data in toxicology studies. Toxicology 2002;66:313–9.10.1093/toxsci/66.2.313Search in Google Scholar
[19] Fraulob JC, Ogg DR, Fernandes SC, Aguila MB, Mandarim de LC. A mouse model of metabolic syndrome: insulin resistance, fatty liver and non-alcoholic fatty pancreas disease (NAFPD) in C57BL/6 mice fed a high fat diet. J Clin Biochem Nutr 2010;46:212–23.10.3164/jcbn.09-83Search in Google Scholar
[20] Thrall M, Weiser MG. Haematology. laboratory procedures for veterinary technicians, 4th ed., Vol. 1. Missouri, USA: Mosby Incorporated, 2002:29–74.Search in Google Scholar
[21] Higgins T, Beutler E, Doumas B. Measurement of haemoglobin in blood. In: Burtis C, Ashwood E, Bruns D, editors. Tietz fundamentals of clinical chemistry, 6th ed., MI, USA: Saunders Elsevier, 2008:524–5.Search in Google Scholar
[22] Todorova I, Simeonova G, Kyuchukova D, Dinev D, Gadjeva V. Reference values of oxidative stress parameters (MDA, SOD, CAT) in dogs and cats. Comp Clin Pathol 2005;13:190–4.10.1007/s00580-005-0547-5Search in Google Scholar
[23] Omaye ST, Turnbull JD, Sauberlich HE. Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol 1979;62:3–11.10.1016/0076-6879(79)62181-XSearch in Google Scholar
[24] Martinek RG. Method for the determination of vitamin E (total tocopherols) in serum. Clin Chem 1964;10:1078–86.10.1093/clinchem/10.12.1078Search in Google Scholar
[25] Okamoto T, Okabe S. Carbon tetrachloride treatment induces anorexia independently of hepatitis in rats. Int J Mol Med 2000;6:181–3.10.3892/ijmm.6.2.181Search in Google Scholar PubMed
[26] Okamoto T, Masuda Y, Kawasaki T, Okabe S. Zaltoprofen prevents carbon tetrachloride-induced reduction of body weight in rats. Int J Mol Med 2001;7:101–4.10.3892/ijmm.7.1.101Search in Google Scholar
[27] Lin Y, Si D, Zhang Z, Liu C. An integrated metabonomic method for profiling of metabolic changes in carbon tetrachloride induced rat urine. Toxicology 2009;256:191–200.10.1016/j.tox.2008.11.018Search in Google Scholar
[28] Carvalho RA, Jones JG, McGuirk C, Sherry AD, Malloy CR. Hepatic gluconeogenesis and Krebs cycle fluxes in a CCl4 model of acute liver failure. NMR Biomed 2002;15:45–51.10.1002/nbm.745Search in Google Scholar
[29] Gergely J, Kulcsar A, Harsfalvi J. Changes in fat metabolism in acute carbon tetrachloride intoxication of rats. Acta Pharmaceut Hungarica 1995;65:3–4.Search in Google Scholar
[30] Jiang L, Huang J, Wang Y, Tang H. Metabonomic analysis reveals the CCl4-induced systems alterations for multiple rat organs. J Proteome Res 2012;11:3848–59.10.1021/pr3003529Search in Google Scholar
[31] Jiang W, Gao M, Sun S, Bi A, Xin Y, Han X, Luo L. Protective effect of L-theanine on carbon tetrachloride-induced acute liver injury in mice. Biochem Biophys Res Commun 2012;422:344–50.10.1016/j.bbrc.2012.05.022Search in Google Scholar
[32] Krahenbuhl S, Weber FL, Jr, Brass EP. Decreased hepatic glycogen content and accelerated response to starvation in rats with carbon tetrachloride-induced cirrhosis. Hepatology 1991;14:1189–5.10.1002/hep.1840140638Search in Google Scholar
[33] Krahenbuhl S, Reichen J. Decreased hepatic glucose production in rats with carbon tetrachloride-induced cirrhosis. J Hepatol 1993;19:64–70.10.1016/S0168-8278(05)80177-1Search in Google Scholar
[34] Lopez-Lirola A, Gonzalez-Reimers E, Martin OR, Santolaria-Fernandez F, Galindo-Martin L, Abreu-Gonzalez P, et al. Protein deficiency and muscle damage in carbon tetrachloride induced liver cirrhosis. Food Chem Toxicol 2003;41:1789–97.10.1016/S0278-6915(03)00218-7Search in Google Scholar
[35] Weber FL, Jr, Macechko PT, Kelson SR, Karajiannis E, Hassan MO. Increased muscle protein catabolism caused by carbon tetrachloride hepatic injury in rats. Gastroenterology 1992;102:1700–6.10.1016/0016-5085(92)91733-KSearch in Google Scholar
[36] Drougard A, Fournel A, Valet P, Knauf C. Impact of hypothalamic reactive oxygen species in the regulation of energy metabolism and food intake. Front Neurosci 2015;9:56.10.3389/fnins.2015.00056Search in Google Scholar PubMed PubMed Central
[37] Spiers JG, Chen H-JC, Sernia C, Lavidis NA. Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress. Front Neurosci 2015;8:456.10.3389/fnins.2014.00456Search in Google Scholar PubMed PubMed Central
[38] Sahin N, Orhan C, Tuzcu M, Sahin K, Kucuk O. The effects of tomato powder supplementation on performance and lipid peroxidation in quail. Poultry Sci 2008;87:276–83.10.3382/ps.2007-00207Search in Google Scholar
[39] Gadupudi GS, Klaren WD, Olivier AK, Klingelhutz AJ, Robertson LW. PCB126-induced disruption in gluconeogenesis and fatty acid oxidation precedes fatty liver in male rats. Toxicol Sci 2016;149:98–110.10.1093/toxsci/kfv215Search in Google Scholar
[40] Lin S, Lai TC, Chen L, Kwok HF, Lau CB-S, Cheung PC. Antioxidant and antiangiogenic properties of phenolic extract from Pleurotus tuber-regium. J Agric Food Chem 2014;62:9488–98.10.1021/jf5031604Search in Google Scholar
[41] Vajdovich P, Szilagyi A, Gaal T. Evaluation of blood lipid peroxidation parameters in carbon tetrachloride (CCl4) toxicity in sheep. Acta Veterinaria Hungarica 1995;43:423–9.Search in Google Scholar
[42] Patience JF, Rossoni-Serao MC, Gutierrez NA. A review of feed efficiency in swine: biology and application. J Anim Sci Biotechnol 2015;6:33.10.1186/s40104-015-0031-2Search in Google Scholar
[43] Jose N, Ajith T, Janardhanan K. Methanol extract of the oyster mushroom, Pleurotus florida, inhibits inflammation and platelet aggregation. Phytother Res Int J Devoted Pharmacol Toxicol Eval Natural Product Derivatives 2004;18:43–6.10.1002/ptr.1355Search in Google Scholar
[44] Lu JM, Lin PH, Yao Q, Chen C. Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J Cell Mol Med 2010;14:840–60.10.1111/j.1582-4934.2009.00897.xSearch in Google Scholar
[45] Mandal A, Karmakar R, Bandyopadhyay S, Chatterjee M. Antihepatotoxic potential of Trianthema portulacastrum in carbon tetrachloride-induced chronic hepatocellular injury in mice: reflection in haematological, histological and biochemical characteristics. Arch Pharmacal Res 1998;21:223–30.10.1007/BF02975279Search in Google Scholar
[46] Saba AB, Oyagbemi AA, Azeez OI. Amelioration of carbon tetrachloride-induced hepatotoxicity and haemotoxicity by aqueous leaf extract of Cnidoscolus aconitifolius in rats 894. Niger J Physiol Sci 2010;25:139–7.Search in Google Scholar
[47] Eshak MG, Hassanane M, Farag IM, Shaffie NM, Abdalla AM. Evaluation of protective and therapeutic role of moringa oleifera leaf extract on CCl4-induced genotoxicity, hemotoxicity and hepatotoxicity in rats. Int J Pharm Tech Res 2015;7:392–15.Search in Google Scholar
[48] Mojzis J, Nicak A, Guzy J, Kron I, Mirossay L. Effect of stobadine on carbon tetrachloride-induced erythrocyte membrane changes in rats. Free Radical Biol Med 1998;24:1347–51.10.1016/S0891-5849(97)00462-0Search in Google Scholar
[49] Arika W, Nyamai D, Musila M, Ngugi M, Njagi E. Hematological markers of in vivo toxicity. J Hematol Thromboembol Dis 2016; 4: 1– 7.Search in Google Scholar
[50] Mohanty J, Nagababu E, Rifkind JM. Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging. Front Physiol 2014;5:84.10.3389/fphys.2014.00084Search in Google Scholar PubMed PubMed Central
[51] Tavazzi B, Di Pierro D, Amorini AM, Fazzina G, Tuttobene M, Giardina B, et al. Energy metabolism and lipid peroxidation of human erythrocytes as a function of increased oxidative stress. Eur J Biochem 2000;267:684–9.10.1046/j.1432-1327.2000.01042.xSearch in Google Scholar PubMed
[52] Tolooei M, Mirzaei A. Effects of Pistacia atlantica extract on erythrocyte membrane rigidity, oxidative stress, and hepatotoxicity induced by CCl4 in rats. Glob J Health Sci 2015;7:46855.10.5539/gjhs.v7n7p32Search in Google Scholar PubMed PubMed Central
[53] Chiu DTY, Liu TZ. Free radical and oxidative damage in human blood cells. J Biomed Sci 1997;4:256–9.10.1007/BF02253426Search in Google Scholar PubMed
[54] Al-Dbass AM, Al-Daihan SK, Bhat RS. Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats. Saudi J Biol Sci 2012;19:303–9.10.1016/j.sjbs.2012.03.004Search in Google Scholar PubMed PubMed Central
[55] Chen TQ, Wu JG, Kan YJ, Yang C, Wu YB, Wu Z. Antioxidant and hepatoprotective activities of crude polysaccharide extracts from lingzhi or reishi medicinal mushroom, Ganoderma lucidum (Agaricomycetes), by ultrasonic-circulating extraction. Int J Med Mushrooms 2018;20:581–93.10.1615/IntJMedMushrooms.2018026536Search in Google Scholar PubMed
[56] Jin M, Jung HJ, Choi JJ, Jeon H, Oh JH, Kim B, Kim S. Activation of selective transcription factors and cytokines by water-soluble extract from Lentinus lepideus. Exp Biol Med 2003;228:749–58.10.1177/153537020322800615Search in Google Scholar PubMed
[57] Gutyj B, Martyshchuk T, Bushueva I, Semeniv B, Parchenko V, Kaplaushenko A, et al. Morphological and biochemical indicators of blood of rats poisoned by carbon tetrachloride and subject to action of liposomal preparation. Regulat Mech Biosyst. 2017;2:304–309.10.15421/021748Search in Google Scholar
[58] Loyke HF, Maksem JA. Hepatocellular injury induced by chronic low-dose CCl4 in spontaneous and renal hypertensive rats: a correlation to the reversal of experimental rat hypertensive models. J Environ Pathol Toxicol Oncol 1992;11:38–42.Search in Google Scholar
[59] Sule O, Abdu A, Kiridi K. Effect of Carica papaya (L) leaves on haematological parameters in CCl4-induced Wistar Albino Rats. 2016;3:1–6.10.9734/BJMMR/2016/13686Search in Google Scholar
[60] Balta S, Demirkol S, Unlu M, Arslan Z, Celik T. Neutrophil to lymphocyte ratio may be predict of mortality in all conditions. Br J Cancer 2013;109:3125.10.1038/bjc.2013.598Search in Google Scholar PubMed PubMed Central
[61] Isaac V, Wu C-Y, Huang C-T, Baune BT, Tseng CL, McLachlan CS. Elevated neutrophil to lymphocyte ratio predicts mortality in medical inpatients with multiple chronic conditions. Medicine 2016;95:e3832.10.1097/MD.0000000000003832Search in Google Scholar PubMed PubMed Central
[62] Karabacak M, Turkdogan KA, Coskun A, Akpinar O, Duman A, Kapci M, et al. Detection of neutrophil-lymphocyte ratio as a serum marker associated with inflammations by acute carbon monoxide poisoning. J Acute Dis 2014;4:305–8.10.1016/j.joad.2015.06.009Search in Google Scholar
[63] Kocak MZ, Fidan K. Could the neutrophil-to-lymphocyte ratio be a marker of acute inflammation in chronic obstructive pulmonary disease? Eurasian J Med Investig 2018;2:8–11.10.14744/ejmi.2018.25744Search in Google Scholar
[64] Tonyali S, Ceylan C, Yahsi S, Karakan MS. Does neutrophil to lymphocyte ratio demonstrate deterioration in renal function? Renal Failure 2018;40:209–12.10.1080/0886022X.2018.1455590Search in Google Scholar PubMed PubMed Central
[65] Illesca P, Valenzuela R, Espinosa A, Echeverría F, Soto-Alarcon S, Ortiz M, et al. Hydroxytyrosol supplementation ameliorates the metabolic disturbances in white adipose tissue from mice fed a high-fat diet through recovery of transcription factors Nrf2, SREBP-1c, PPAR-γ and NF-κB. Biomed Pharmacother 2019;109:2472–81.10.1016/j.biopha.2018.11.120Search in Google Scholar PubMed
[66] Valenzuela R, Echeverria F, Ortiz M, Rincón-Cervera MÁ, Espinosa A, Hernandez-Rodas MC, et al. Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice. Lipids Health Dis 2017;16:64.10.1186/s12944-017-0450-5Search in Google Scholar PubMed PubMed Central
[67] Pisoschi AM, Negulescu GP. Methods for total antioxidant activity determination: a review. Biochem Anal Biochem 2011;1:106.10.4172/2161-1009.1000106Search in Google Scholar
[68] Halvorsen BL, Holte K, Myhrstad MC, Barikmo I, Hvattum E, Remberg SF, et al. A systematic screening of total antioxidants in dietary plants. J Nutr 2002;132:461–71.10.1093/jn/132.3.461Search in Google Scholar PubMed
[69] Sherif IO. The effect of natural antioxidants in cyclophosphamide-induced hepatotoxicity: role of Nrf2/HO-1 pathway. Int Immunopharmacol 2018;61:29–36.10.1016/j.intimp.2018.05.007Search in Google Scholar PubMed
[70] Kramarenko GG, Hummel SG, Martin SM, Buettner GR. Ascorbate reacts with singlet oxygen to produce hydrogen peroxide. Photochem Photobiol 2006;82:1634–7.10.1111/j.1751-1097.2006.tb09823.xSearch in Google Scholar
[71] Buettner GR. The pecking order of free radicals and antioxidants: lipid peroxidation, α-tocopherol, and ascorbate. Arch Biochem Biophys 1993;300:535–43.10.1006/abbi.1993.1074Search in Google Scholar PubMed
[72] Ramadan MF, Kroh LW, Mörsel JT. Radical scavenging activity of black cumin (Nigella sativa L.), coriander (Coriandrum sativum L.), and niger (Guizotia abyssinica Cass.) crude seed oils and oil fractions. J Agric Food Chem 2003;51:6961–9.10.1021/jf0346713Search in Google Scholar PubMed
© 2020 Walter de Gruyter GmbH, Berlin/Boston
