Protective effects of fungal β-(1→3)-D-glucan against oxidative stress cytotoxicity induced by depleted uranium in isolated rat hepatocytes

Abstract

Previous reports suggested that certain carbohydrate polymers, such as β-(1→3)-D-glucan, may possess free radical scavenging activity. The present study examined the free radical scavenging activity of a carbohydrate polymer, β-(1→3)-D-glucan against oxidative stress induced by depleted uranium in isolated rat hepatocytes. Addition of U (VI) (uranyl acetate) to isolated rat hepatocytes results in reactive oxygen species (ROS) formation, rapid glutathione depletion, mitochondrial membrane potential collapse and lysosomal membrane rupture before hepatocyte lysis occurred. Our results showed that quite similar to silymarin, which is a known antioxidant and radical scavenger, tiny concentration of β-glucan (138 nM) very successfully protected the hepatocytes against cell lysis and all oxidative stress cytotoxicity endpoints caused by depleted uranium including ROS formation, glutathione depletion, decreased mitochondrial membrane potential, lysosomal membrane rupture and caspase 3 activity increase. In conclusion, our results confirmed the antioxidant and radical scavenging activity of β-(1→3)-D-glucan and suggested this compound and silymarin as possible drug candidates for prophylaxis and treatment against depleted uranium toxic effects.

Keywords

oxidative stress cytoprotection/glutathione hepatic toxicology (1→3)-β-D-glucan depleted uranium

References

Kogan G. (1→3, 1→6)-β-D-glucans of yeasts and fungi and their biological activity. Studies in Natural Products Chemistry 2000; 23: 107-152.

Sener G. , Toklu H. , Ercan F. , Erkanli G. Protective effect of β-glucan against oxidative organ injury in a rat model of sepsis. Int Immunopharm 2005 ; 5: 1387- 1396.

Onderdonk AB , Cisneros RL , Hinkson P. , Ostroff G. Anti-infective effect of poly-β-1-6-glucotriosyl-β-1-3- glucopyranose glucan in vivo . Infect Immun 1992; 60: 1642-1647.

Kernoddle DS , Gates H. , Kaiser AB Prophylactic anti-infective activity of poly- [1-6]-β-D-glucopyranosyl-[1-3]-β-d-glucopyranose glucan in a guinea pig model of staphylococcal wound infection. Antimicrob Agents Chemother 1998; 42: 545-549.

Cleary JA , Kelly GE , Husband AJ The effect of molecular weight and β-1,6-linkages on priming of macrophage function in mice by (1,3)-β-D-glucan. Immunol Cell Biol 1999; 77: 395-403.

Vetvicka V. , Yvin JC Effects of marine β-1, 3 glucan on immune reactions. Int Immunopharmacol 2004; 4: 721-730.

Wei D. , Williams D. , Browder W. Activation of AP-1 and SP1 correlates with wound growth factor gene expression in glucan-treated human fibroblasts. Int Immunopharmacol 2002; 2: 1163-1172.

Soltys J. , Quinn MT Modulation of endotoxin- and enterotoxin-induced cytokine release by in vivo treatment with β-(1,6)-branched β-(1,3)-glucan. Infect Immun 1999; 67: 244-252.

Engstad CS , Engstad RE , Olsen JO , Osterud B. The effect of soluble β-1,3-glucan and lipopolysaccharide on cytokine production and coagulation activation in whole blood. Int Immunopharmacol 2002; 2: 1585-1597.

10.

Ljungman AG , Leanderson P. , Tagesson C. (1→3)-βd-glucan stimulates nitric oxide generation and cytokine mRNA expression in macrophages. Environ Toxicol Pharmacol 1998; 5: 273-281.

11.

Nicolosi R. , Bell SJ , Bistrian BR , Greenberg I. , Forse RA , Blackburn GL Plasma lipid changes after supplementation with β-glucan fiber from yeast. Am J Clin Nutr 1999; 70: 208-212.

12.

Slamenova D. , Labaj J. , Krizkova L. , Kogan G. , Sandula J. , Bresgen N. , et al. Protective effects of fungal (1→3)-beta-D-glucan derivatives against oxidative DNA lesions in V79 hamster lung cells. Cancer Lett 2003; 198: 153-160.

13.

Toklu HZ , Sehirli AO , Velioglu-Ogünç A. , Cetinel S. , Sener G. Acetaminophen-induced toxicity is prevented by β-D-glucan treatment in mice. Eur J Pharmacol 2006; 543: 133-140.

14.

Pourahmad J. , Ghashang M. , Ettehadi HA , Ghalandari R. A search for cellular and molecular mechanisms involved in depleted uranium (DU) toxicity . Environ Toxicol 2006; 21: 349-354.

15.

Jiang GCT , Tidwell K. , Mc Laughlin BA , Cai J. , Gupta RC , Milatovic D. , et al. Neurotoxic potential of depleted uranium effects in primary cortical neuron cultures and in caenorhabditis elegans. Toxicol Sci 2007; 99: 553-565.

16.

Linares V. , Albina ML , Belles M. , Mayayo E. , Sanchez DJ , Domingo JL Combined action of uranium and stress in the rat II.Effects on male reproduction . Toxicol Lett 2005; 158: 186-195.

17.

Bertell R. Occupational hazards of war depleted uranium: all the questions about and gulf war syndrome are not yet answered. Int J Health Serv 2006; 36: 503-520.

18.

Squibb KS , Mc Diarmid MA Depleted uranium exposure and health effects in Gulf War veterans . Phil Trans R Soc B 2006; 361: 639-648.

19.

Wise SS , Thompson WD , Aboueissa AEM , Mason MD , Wise JP Particulate depleted uranium is cytotoxic and clastogenic to human lung cells . Chem Res Toxicol 2007; 20: 815-820.

20.

Bleise A. , Danesi PR , Burkart W. Properties, use and health effects of depleted uranium (DU): a general overview . J Environ Radioact 2003; 64: 93-112.

21.

Bosque MA , Domingo JL , Llobet JM , Corbella J. Embryotoxicity and teratogenicity of uranium in mice following subcutaneous administration of uranyl acetate. Biol Trace Element Res 1992; 36: 109-118.

22.

Domingo JL Reproductive and developmental toxicity of natural and depleted uranium: a review. Reprod Toxicol 2001; 15: 603-609.

23.

Miller AC , Brooks K. , Stewart M. , Anderson B. , Lin S. , McClain D. , et al. Genomic instability in human osteoblast cells after exposure to depleted uranium: delayed lethality and micronuclei formation. J Environ Radioact 2003; 64: 247-259.

24.

Yazzie M. , Gamble SL , Civitello ER , Stearns DM Uranyl acetate causes DNA single strand breaks in vitro in the presence of ascorbate (VitaminC). Chem Res Toxico 2003 ; 16: 524-530.

25.

Pradeep K. , Mohan CVR , Gobianand K. , Karthikeyan S. Silymarin modulates the oxidant-antioxidant imbalance during diethylnitrosamine induced oxidative stress in rats. Eur J Pharmacol 2007; 560: 110-116.

26.

El-Shitany NA , El- Haggar S. , El-desoky K. Silymarin prevents adriamycin-induced cardiotoxicity and nephrotoxicity in rats. Food Chem Toxicol 2008; 46: 2422-2428.

27.

Alidoost F. , Gharagozloo M. , Bagherpour B. , Jafarian A. , Sajjadi SE , Hourfar H. , et al. Effects of silymarin on the proliferation and glutathione levels of peripheral blood mononuclear cells from β-thalassemia major patients. Int Immunopharmacol 2006; 6: 1305-1310.

28.

Elizabeth K. , Rao MNA. Oxygen radical scavenging activity of curcumin . Int J Pharm 1990; 58: 237-240.

29.

Pourahmad J. , O’Brien PJ A comparison of hepatocyte cytotoxic mechanisms for Cu2+and Cd2+. Toxicology 2000 ; 143: 263-273.

30.

Shen HM , Shi CY , Shen Y. , Ong CN Detection of elevated reactive oxygen species level in cultured rat hepatocytes treated with aflatoxin B1. Free Radic Biol Med 1996; 21: 139-146.

31.

Hissin J. , Hilf R. A fluorometric method for determination of oxidised and reduced glutathion in tissues. Anal Biochem 1976; 74: 214-226.

32.

Andersson BS , Aw TY , Jones DP Mitochondrial transmembrane potential and pH gradient during anoxia. Am J Physiol 1987 ; 252: C349-C355.

33.

Pourahmad J. , Rabiei M. , Jokar F. , O’Brien PJ A comparison of hepatocyte cytotoxic mechanisms for chromate and arsenite . Toxicology 2005 ; 206: 449-460.

34.

Novak RF , Kharasch ED , Wendel NK Nitrofurantoin stimulated proteolysis in human erythrocytes: a novel index of toxic insult by nitroaromatics. J Pharmacol Exp Ther 1988; 24: 439-444.

35.

Sakahira H. Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis . Nature 1998; 391: 96-99.

36.

Rezaie M. , Rasekh HR , Ahmadiani A. , Pourahmad J. Involvment of subcellular organells in inflammatory pain induced oxidative stress and apoptosis in the rat hepatocytes. Arch Iran Med 2008; 11: 407-417.

37.

Kroemer G. , Reed JC Mitochondrial control of cell death. Nat Med 2000; 6: 513-519.

38.

Brown GD , Gordon S. Fungal β-glucans and mammalian immunity. Immunity 2003; 19: 311-315.

39.

Williams DL , Ha T. , Li C. , Kalbfleisch JH , Laffan JJ , Ferguson DA Inhibiting early activation of tissue nuclear factor-EB and nuclear factor interleukin 6 with (1→3) β-D-glucan increases long-term survival in polymicrobial sepsis. Surgery 1999; 126: 54-65.

40.

Hashimoto T. , Ohno N. , Adachi Y. , Yadomae T. Enhanced production of inducible nitric oxide synthase by B-glucan in mice. FEMS Immunol Med Microbiol 1997; 19: 131-135.

41.

Sener G. , Toklu HZ , Cetinel S. β-Glucan protects against chronic nicotine-induced oxidative damage in rat kidney and bladder. Environ Toxicol Pharmacol 2007; 23: 25-32.

42.

Toklu HZ , Sener G. , Jahovic N. , Uslu B. , Arbak S. , Yegen BC β-glucan protects against burn-induced oxidative organ damage in rats . Int Immunopharmacol 2006; 6: 156-169.

43.

Sener G. , Eksioglu-Demiralp E. , Cetiner M. , Ercan F. , Yegen BC β-glucan ameliorates methotrexateinduced oxidative organ injury via its antioxidant and immunomodulatoryeffects. Eur J Pharmacol 2006; 542: 170-178.