期刊论文详细信息
BMC Complementary and Alternative Medicine
Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative stress in acetaminophen-induced hepato-renal injury
Mohamed F Salem3  Rehab M Samaka2  Rania M Azmy1  Yahya M Naguib4 
[1]Department of Medical Biochemistry, Faculty of Medicine, Menoufia University, Menoufia, Egypt
[2]Department of Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
[3]Genetic Engineering and Biotechnology Research Institute, Sadat City University, Menoufia, Egypt
[4]Department of Clinical Physiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
关键词: Antioxidant;    Acetaminophen;    Mitochondrial dysfunction;    Acute hepato-renal injury;    Oxidative stress;    Pleurotus ostreatus;   
Others  :  1084772
DOI  :  10.1186/1472-6882-14-494
 received in 2014-03-10, accepted in 2014-12-10,  发布年份 2014
PDF
【 摘 要 】

Background

Acetaminophen (APAP)-induced toxicity is a predominant cause of acute hepatic and renal failure. In both humans and rodents toxicity begins with a reactive metabolite that binds to proteins. This leads to mitochondrial dysfunction and nuclear DNA fragmentation resulting in necrotic cell death. Pleurotus ostreatus (an edible oyster mushroom) is well recognized as a flavourful food, as well as a medicinal supplement. In the present study, we evaluated the role of Pleurotus ostreatus in the protection against APAP-induced hepato-renal toxicity. We also explored the mechanism by which Pleurotus ostreatus exerts its effects.

Methods

Ninety adult male Swiss albino mice were divided into three groups (30 mice/group). Mice were offered normal diet (control and APAP groups), or diet supplemented with 10% Pleurotus ostreatus (APAP + Pleurotus ostreatus) for 10 days. Mice were either treated with vehicle (control group, single intra-peritoneal injection.), or APAP (APAP and APAP + Pleurotus ostreatus groups, single intra-peritoneal injection, 500 mg/kg), 24 hours after the last meal.

Results

APAP increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) glutamate dehydrogenase (GDH), creatinine, blood urea nitrogen (BUN), urinary kidney injury molecule-1 (KIM-1), and hepatic and renal malondialdehyde (MDA) content. APAP decreased hepatic and renal glutathione (GSH) content, as well as glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Supplementation with Pleurotus ostreatus significantly reduced APAP-induced elevated levels of ALT, AST, GDH, creatinine, BUN, KIM-1and MDA, while GSH level, and GSH-Px and SOD activities were significantly increased. Our findings were further validated by histopathology; treatment with Pleurotus ostreatus significantly decreased APAP-induced cell necrosis in liver and kidney tissues.

Conclusions

We report here that the antioxidant effect of Pleurotus ostreatus opposes mitochondrial dysfunction and oxidative stress accompanying APAP over-dose, with subsequent clinically beneficial effects on liver and kidney tissues.

【 授权许可】

   
2014 Naguib et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150113164206747.pdf 1324KB PDF download
Figure 4. 83KB Image download
Figure 3. 50KB Image download
Figure 2. 142KB Image download
Figure 1. 137KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】
  • [1]Gum SI, Cho MK: Recent updates on acetaminophen hepatotoxicity: the role of nrf2 in hepatoprotection. Toxicol Res 2013, 29(3):165-172.
  • [2]Whitcomb DC: Acetaminophen poisoning and liver function. N Engl J Med 1994, 331(19):1311-1312.
  • [3]Whitcomb DC, Block GD: Association of acetaminophen hepatotoxicity with fasting and ethanol use. JAMA 1994, 272(23):1845-1850.
  • [4]Jaeschke H, McGill MR, Ramachandran A: Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity. Drug Metab Rev 2012, 44(1):88-106.
  • [5]McGill MR, Williams CD, Xie Y, Ramachandran A, Jaeschke H: Acetaminophen-induced liver injury in rats and mice: comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity. Toxicol Appl Pharmacol 2012, 264(3):387-394.
  • [6]Bonkovsky HL, Kane RE, Jones DP, Galinsky RE, Banner B: Acute hepatic and renal toxicity from low doses of acetaminophen in the absence of alcohol abuse or malnutrition: evidence for increased susceptibility to drug toxicity due to cardiopulmonary and renal insufficiency. Hepatology (Baltimore, Md) 1994, 19(5):1141-1148.
  • [7]Satirapoj B, Lohachit P, Ruamvang T: Therapeutic dose of acetaminophen with fatal hepatic necrosis and acute renal failure. J Med Assoc Thai 2007, 90(6):1244-1247.
  • [8]McGill MR, Sharpe MR, Williams CD, Taha M, Curry SC, Jaeschke H: The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. J Clin Investig 2012, 122(4):1574-1583.
  • [9]Dimova S, Hoet PH, Dinsdale D, Nemery B: Acetaminophen decreases intracellular glutathione levels and modulates cytokine production in human alveolar macrophages and type II pneumocytes in vitro. Int J Biochem Cell Biol 2005, 37(8):1727-1737.
  • [10]Dimova S, Hoet PH, Nemery B: Paracetamol (acetaminophen) cytotoxicity in rat type II pneumocytes and alveolar macrophages in vitro. Biochem Pharmacol 2000, 59(11):1467-1475.
  • [11]Stern ST, Bruno MK, Horton RA, Hill DW, Roberts JC, Cohen SD: Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity II. Possible involvement of the gamma-glutamyl cycle. Toxicol Appl Pharmacol 2005, 202(2):160-171.
  • [12]Askari F, Rashidkhani B, Hekmatdoost A: Cinnamon may have therapeutic benefits on lipid profile, liver enzymes, insulin resistance, and high-sensitivity C-reactive protein in nonalcoholic fatty liver disease patients. Nutr Res 2013, 34(2):143-148.
  • [13]Capellini VK, Celotto AC, Baldo CF, Olivon VC, Viaro F, Rodrigues AJ, Evora PR: Diabetes and vascular disease: basic concepts of nitric oxide physiology, endothelial dysfunction, oxidative stress and therapeutic possibilities. Curr Vasc Pharmacol 2010, 8(4):526-544.
  • [14]Fiorentino TV, Prioletta A, Zuo P, Folli F: Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Curr Pharm Des 2013, 19(32):5695-5703.
  • [15]Manna P, Sil PC: Impaired redox signaling and mitochondrial uncoupling contributes vascular inflammation and cardiac dysfunction in type 1 diabetes: protective role of arjunolic acid. Biochimie 2012, 94(3):786-797.
  • [16]Moraes TB, Dalazen GR, Jacques CE, de Freitas RS, Rosa AP, Dutra-Filho CS: Glutathione metabolism enzymes in brain and liver of hyperphenylalaninemic rats and the effect of lipoic acid treatment. Metab Brain Dis 2014, 29(2):609-615.
  • [17]Sedeek M, Nasrallah R, Touyz RM, Hebert RL: NADPH oxidases, reactive oxygen species, and the kidney: friend and foe. J Am Soc Nephrol 2013, 24(10):1512-1518.
  • [18]Chen J: Heme oxygenase in neuroprotection: from mechanisms to therapeutic implications. Rev Neurosci 2014, 25(2):269-280.
  • [19]Chen YR, Zweier JL: Cardiac mitochondria and reactive oxygen species generation. Circ Res 2014, 114(3):524-537.
  • [20]Uttara B, Singh AV, Zamboni P, Mahajan RT: Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 2009, 7(1):65-74.
  • [21]Wasser SP: Current findings, future trends, and unsolved problems in studies of medicinal mushrooms. Appl Microbiol Biotechnol 2011, 89(5):1323-1332.
  • [22]Anandhi R, Annadurai T, Anitha TS, Muralidharan AR, Najmunnisha K, Nachiappan V, Thomas PA, Geraldine P: Antihypercholesterolemic and antioxidative effects of an extract of the oyster mushroom, Pleurotus ostreatus, and its major constituent, chrysin, in Triton WR-1339-induced hypercholesterolemic rats. J Physiol Biochem 2013, 69(2):313-323.
  • [23]Jedinak A, Sliva D: Pleurotus ostreatus inhibits proliferation of human breast and colon cancer cells through p53-dependent as well as p53-independent pathway. Int J Oncol 2008, 33(6):1307-1313.
  • [24]Jesenak M, Majtan J, Rennerova Z, Kyselovic J, Banovcin P, Hrubisko M: Immunomodulatory effect of pleuran (beta-glucan from Pleurotus ostreatus) in children with recurrent respiratory tract infections. Int Immunopharmacol 2013, 15(2):395-399.
  • [25]Trzebska-Jeske I, Rutkowska U, Zielinska Z: [Comparison of the methods of estimating the energy value of cooked meals]. Rocz Panstw Zakl Hig 1979, 30(3):277-284.
  • [26]Asp NG, Johansson CG, Hallmer H, Siljestrom M: Rapid enzymatic assay of insoluble and soluble dietary fiber. J Agric Food Chem 1983, 31(3):476-482.
  • [27]Bidlingmeyer BA, Cohen SA, Tarvin TL: Rapid analysis of amino acids using pre-column derivatization. J Chromatogr 1984, 336(1):93-104.
  • [28]Muldrew KL, James LP, Coop L, McCullough SS, Hendrickson HP, Hinson JA, Mayeux PR: Determination of acetaminophen-protein adducts in mouse liver and serum and human serum after hepatotoxic doses of acetaminophen using high-performance liquid chromatography with electrochemical detection. Drug Metab Dispos 2002, 30(4):446-451.
  • [29]Lindena J, Trautschold I: Catalytic enzyme activity concentration in plasma of man, sheep, dog, cat, rabbit, guinea pig, rat and mouse. Approach to a quantitative diagnostic enzymology, I. Communication. J Clin Chem Clin Biochem 1986, 24(1):11-18.
  • [30]Perrone RD, Madias NE, Levey AS: Serum creatinine as an index of renal function: new insights into old concepts. Clin Chem 1992, 38(10):1933-1953.
  • [31]Schumann G, Aoki R, Ferrero CA, Ehlers G, Ferard G, Gella FJ, Jorgensen PJ, Kanno T, Kessner A, Klauke R, Kristiansen N, Lessinger JM, Linsinger TP, Misaki H, Mueller MM, Panteghini M, Pauwels J, Schiele F, Schimmel HG, Vialle A, Weidemann G, Schumann G: International Federation of Clinical Chemistry and Laboratory Medicine: IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. Clin Chem Lab Med 2006, 44(9):1146-1155.
  • [32]Ichimura T, Hung CC, Yang SA, Stevens JL, Bonventre JV: Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol 2004, 286(3):F552-F563.
  • [33]Zhou Y, Vaidya VS, Brown RP, Zhang J, Rosenzweig BA, Thompson KL, Miller TJ, Bonventre JV, Goering PL: Comparison of kidney injury molecule-1 and other nephrotoxicity biomarkers in urine and kidney following acute exposure to gentamicin, mercury, and chromium. Toxicol Sci 2008, 101(1):159-170.
  • [34]Jacobson B, Quigley G, Lockitch G: Adaptation of glutathione peroxidase assay to the Technicon RA-1000. Clin Chem 1988, 34(10):2164-2165.
  • [35]Kuthan H, Haussmann HJ, Werringloer J: A spectrophotometric assay for superoxide dismutase activities in crude tissue fractions. Biochem J 1986, 237(1):175-180.
  • [36]Satoh K: Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 1978, 90(1):37-43.
  • [37]Wang XJ, Sun Z, Chen W, Eblin KE, Gandolfi JA, Zhang DD: Nrf2 protects human bladder urothelial cells from arsenite and monomethylarsonous acid toxicity. Toxicol Appl Pharmacol 2007, 225(2):206-213.
  • [38]O’Brien PJ, Slaughter MR, Polley SR, Kramer K: Advantages of glutamate dehydrogenase as a blood biomarker of acute hepatic injury in rats. Lab Anim 2002, 36(3):313-321.
  • [39]Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S: The current state of serum biomarkers of hepatotoxicity. Toxicology 2008, 245(3):194-205.
  • [40]Ghosh J, Das J, Manna P, Sil PC: Acetaminophen induced renal injury via oxidative stress and TNF-alpha production: therapeutic potential of arjunolic acid. Toxicology 2010, 268(1–2):8-18.
  • [41]Sabbisetti VS, Ito K, Wang C, Yang L, Mefferd SC, Bonventre JV: Novel assays for detection of urinary KIM-1 in mouse models of kidney injury. Toxicol Sci 2012, 131(1):13-25.
  • [42]Placke ME, Ginsberg GL, Wyand DS, Cohen SD: Ultrastructural changes during acute acetaminophen-induced hepatotoxicity in the mouse: a time and dose study. Toxicol Pathol 1987, 15(4):431-438.
  • [43]Mazer M, Perrone J: Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestations, and management. J Med Toxicol 2008, 4(1):2-6.
  • [44]Blantz RC: Acetaminophen: acute and chronic effects on renal function. Am J Kidney Dis 1996, 28(1 Suppl 1):S3-S6.
  • [45]Moon YJ, Wang X, Morris ME: Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro 2006, 20(2):187-210.
  • [46]Lauterburg BH, Mitchell JR: Toxic doses of acetaminophen suppress hepatic glutathione synthesis in rats. Hepatology (Baltimore, Md) 1982, 2(1):8-12.
  • [47]Mitchell JR: Acetaminophen toxicity. N Engl J Med 1988, 319(24):1601-1602.
  • [48]Meyers LL, Beierschmitt WP, Khairallah EA, Cohen SD: Acetaminophen-induced inhibition of hepatic mitochondrial respiration in mice. Toxicol Appl Pharmacol 1988, 93(3):378-387.
  • [49]Panatto JP, Jeremias IC, Ferreira GK, Ramos AC, Rochi N, Goncalves CL, Daufenbach JF, Jeremias GC, Carvalho-Silva M, Rezin GT, Scaini G, Streck EL: Inhibition of mitochondrial respiratory chain in the brain of rats after hepatic failure induced by acetaminophen. Mol Cell Biochem 2011, 350(1–2):149-154.
  • [50]Kon K, Kim JS, Jaeschke H, Lemasters JJ: Mitochondrial permeability transition in acetaminophen-induced necrosis and apoptosis of cultured mouse hepatocytes. Hepatology (Baltimore, Md) 2004, 40(5):1170-1179.
  • [51]Masubuchi Y, Suda C, Horie T: Involvement of mitochondrial permeability transition in acetaminophen-induced liver injury in mice. J Hepatol 2005, 42(1):110-116.
  • [52]Reid AB, Kurten RC, McCullough SS, Brock RW, Hinson JA: Mechanisms of acetaminophen-induced hepatotoxicity: role of oxidative stress and mitochondrial permeability transition in freshly isolated mouse hepatocytes. J Pharmacol Exp Ther 2005, 312(2):509-516.
  • [53]Hinson JA, Reid AB, McCullough SS, James LP: Acetaminophen-induced hepatotoxicity: role of metabolic activation, reactive oxygen/nitrogen species, and mitochondrial permeability transition. Drug Metab Rev 2004, 36(3–4):805-822.
  • [54]Manna P, Das J, Sil PC: Role of sulfur containing amino acids as an adjuvant therapy in the prevention of diabetes and its associated complications. Curr Diabetes Rev 2013, 9(3):237-248.
  文献评价指标  
  下载次数:14次 浏览次数:30次