Barium chloride induces redox status unbalance, upregulates cytokine genes expression and confers hepatotoxicity in rats—alleviation by pomegranate peel
Abstract
The present study was performed to establish the therapeutic efficacy of pomegranate peel against barium chloride induced liver injury. Adult rats were divided into four groups of six animals each: group I, serving as controls, received distilled water; group II received by their drinking water 67 ppm of BaCl2; group III received both 67 ppm of BaCl2 by the same way than group II and 5 % of pomegranate peel (PP) via diet; group IV received 5 % of PP. Analysis by HPLC/MS of PP showed its rich composition in flavonoids such as gallic acid, castalin, hyperin, quercitrin, syringic acid, and quercetin. The protective effects of pomegranate peel against hepatotoxicity induced by barium chloride were assessed using biochemical parameters and histological studies. Exposure of rats to barium caused oxidative stress in the liver as evidenced by an increase in malondialdehyde (MDA), lipid hydroperoxides (LOOHs), H2O2 and advanced oxidation protein product (AOPP) levels, and lactate dehydrogenase (LDH), gamma glutamyl transpeptidase (GGT), alanine aminotransferase (AST) and aspartate aminotransferase (ALT) activities, a decrease in catalase (CAT) and glutathione peroxidase (GPx) activities, glutathion (GSH), non-protein thiol (NPSH), vitamin C levels, and Mn-SOD gene expression. Liver total MT levels, MT-1, and MT-2 and pro-inflammatory cytokine genes expression like TNF-α, IL-1β and IL-6 were increased. Pomegranate peel, supplemented in the diet of barium-treated rats, showed an improvement of all the parameters indicated above.
The present work provided ethnopharmacological relevance of pomegranate peel against the toxic effects of barium, suggesting its beneficial role as a potential antioxidant.
Keywords
Barium chloride Rats Hepatotoxicity Pro-inflammatory cytokines Metallothionein genes expression Pomegranate peelAbbreviations
- ALT
Alanine aminotransferase
- AOPP
Advanced oxidation protein product
- AST
Aspartate aminotransferase
- Ba
Barium
- BaCl2
Barium chloride
- CAT
Catalase
- DNA
Desoxyribonucleic acid
- DNPH
Dinitrophenyl hydrazine
- DTNB
5,5-Dithiobis-2-nitrobenzoic acid
- FP
Forward primer
- GAPDH
Glyceraldehyde 3- phosphate dehydrogenase
- GGT
Gamma glutamyl transpeptidase
- GPx
Glutathione peroxidase
- GSH
Glutathion
- H2O2
Hydrogen peroxide
- HPLC
High-performance liquid chromatography
- IL1-β
Interleukin-1β
- IL-6
Interleukin-6
- LDH
Lactate dehydrogenase
- LD50
Lethal dose
- LOOHs
Lipid hydroperoxides
- MDA
Malondialdehyde
- NPSH
Non-protein thiol
- PP
Pomegranate peel
- PPE
Pomegranate peel extract
- RNA
Ribonucleic acid
- ROS
Reactive oxygen species
- RP
Reverse primer
- SOD
Superoxide dismutase
- TBA
Thiobarbituric acid
- TBARS
Thiobarbituric acid-reactive substances
- TNF-α
Tumor necrosis factor-α
Notes
Acknowledgments
This work was supported by the Ministry of Higher Education and Scientific Research in Tunisia (UR/ 11ES-70). The authors are indebted to Mrs Raoudha Ben Amar Abdennadher and to Mr Chedly TMAR for their skilful technical assistance.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
Ethical approval
The general guidelines for the use and care of living animals in scientific investigations were followed (Council of European Communities 1986). The handling of the animals was approved by the Tunisian Ethical Committee for the Care and Use of laboratory animals.
References
- Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126CrossRefGoogle Scholar
- Ananda S, Shaohua Z, Liang L (2013) Fatal barium chloride poisoning: four cases report and literature review. Am J Forensic Med Pathol 34:115–118CrossRefGoogle Scholar
- Arun N, Singh DP (2012) Punica granatum: a review on pharmacological and therapeutic properties. IJPSR 3:1240–1245Google Scholar
- Aschner M, Syversen T (2005) Methylmercury: recent advances in the understanding of its neurotoxicity. Ther Drug Monit 27:278–283CrossRefGoogle Scholar
- Ben Amara I, Soudani N, Troudi A, Bouaziz H, Boudawara T, Zeghal N (2011) Antioxidant effect of vitamin E and selenium on hepatotoxicity induced by dimethoate in female adult rats. Ecotox Environ Saf 74:811–819CrossRefGoogle Scholar
- Burton A (2003) Chemoprevention, eat ginger, rub on pomegranate. Lancet Oncol 4:715CrossRefGoogle Scholar
- Catalgol BK, Ozden S, Alpertunga B (2007) Effects of trichlorfon on malondialdehyde and antioxidant system in human erythrocytes. Toxicol In Vitro 21:1538–1544CrossRefGoogle Scholar
- Council of European Communities (1986) Council instructions about the protection of living animals used in scientific investigations. Off J Eur Commun (JO 86/609/CEE) L358. 1–18.Google Scholar
- Dallas CE, Williams PL (2001) Barium: rationale for a new oral reference dose. J Toxicol Environ Health B: Crit Rev 4:395–429CrossRefGoogle Scholar
- Dayer JM (2003) The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis. Rheumatology 42(Suppl 2):ii3–10Google Scholar
- De Nardin E (2001) The role of inflammatory and immunological mediators in periodontitis and cardiovascular disease. Ann Periodontol 6:30–40CrossRefGoogle Scholar
- De Nigris F, Balestrieri ML, Williams-Ignarro S, D'Armiento FP, Fiorito C, Ignarro LJ, Napoli C (2007) The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial functions in obese Zucker rats. Nitric Oxide 17:50–54CrossRefGoogle Scholar
- Dietz DD, Elwell MR, Davis WE Jr, Meirhenry EF (1992) Subchronic toxicity of barium chloride dihydrate administered to rats and mice in the drinking water. Fundam Appl Toxicol 19:527–537CrossRefGoogle Scholar
- Draper HH, Hadley M (1990) Malondialdehyde determination as an index of lipid peroxidation. Methods Enzymol 86:421–431CrossRefGoogle Scholar
- Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77CrossRefGoogle Scholar
- El-Sharaky AS, Newairy AA, Badreldeen MM, Eweda SM, Sheweita SA (2007) Protective role of selenium against renal toxicity induced by cadmium in rats. Toxicology 235:185–193CrossRefGoogle Scholar
- Flohe L, Gunzler WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114–121CrossRefGoogle Scholar
- Gracious RR, Selvasubramanian S, Jayasundar S (2001) Immunomodulatory activity of Punica granatum in rabbits—a preliminary study. J Ethnopharmacol 78:85–87CrossRefGoogle Scholar
- Halliwell B, Rafter J, Jenner A (2005) Health promotion by flavonoids, tocopherols, tocotrienols and other phenols: direct or indirect effects? Antioxidant or not? Am J Clin Nutr 8:268S–276SGoogle Scholar
- Huang C, Yang Y, Li WX, Wu XQ, Li XF, Ma TT, Zhang L, Meng XM, Li J (2015) Hyperin attenuates inflammation by activating PPAR-γ in mice with acute liver injury (ALI) and LPS-induced RAW264.7 cells. Int Immunopharmacol 29:440–447CrossRefGoogle Scholar
- Hossin Labib Ahmed F (2009) Effect of pomegranate (Punica granatum) peels and it’s extract on obese hypercholesterolemic rats. Pakistan J Nut 8:1251–1257CrossRefGoogle Scholar
- Jacobs IA, Taddeo J, Kelly K, Valenziano C (2002) Poisoning as a result of barium styphnate explosion. Am J Ind Med 41:285–288CrossRefGoogle Scholar
- Jacques-Silva MC, Nogueira CW, Broch LC (2001) Diphenyldiselenide and ascorbic acid changes deposition of selenium and ascorbic acid in liver and brain of mice. Pharmacol Toxicol 88:119–125CrossRefGoogle Scholar
- Jager J, Gremeaux T, Cormont M, Le Marchand-Brustel Y, Tanti JF (2007) Interleukin- 1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology 148:241–251CrossRefGoogle Scholar
- Jaruga B, Hong F, Kim WH, Gao B (2004) IFN-gamma/STAT1 acts as a proinflammatory signal in T cell-mediated hepatitis via induction of multiple chemokines and adhesion molecules: a critical role of IRF-1. Am J Physiol Gastrointest Liver Physiol 287:1044–1052CrossRefGoogle Scholar
- Jiang ZY, Hunt JV, Wolff SP (1992) Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low-density lipoprotein. Anal Biochem 202:384–389CrossRefGoogle Scholar
- Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR (1974) Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11:151–169CrossRefGoogle Scholar
- Kalender S, Ogutcu A, Uzunhisarcikli M, Açikgoz F, Durak D, Ulusoy Y, Kalender Y (2005) Diazinon-induced hepatotoxicity and protective effect of vitamin E on some biochemical indices and ultrastructural changes. Toxicology 211:197–206CrossRefGoogle Scholar
- Kara H, Karatas F, Canatan H, Servi K (2005) Effects of exogenous metallothionein on acute cadmium toxicity in rats. Biol Trace Elem Res 104:223–232CrossRefGoogle Scholar
- Kidd PM (1997) Glutathione: Systemic protectant against oxidative and free radical damage. Altern Med Rev 2:155–1576Google Scholar
- Klaassen CD, Liu J, Diwan BA (2009) Metallothionein protection of cadmium toxicity. Toxicol Appl Pharmacol 238:215–220CrossRefGoogle Scholar
- Kresse R, Baudis U, Jäger P, Riechers H H, Wagner H, Winkler J, Wolf HU (2007) Barium and barium compounds. In: Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Verlag GmbH & Co. kGaA.. http://www.mrw.interscience.wiley.com/emrw/978352 7306732/ueic/article/a03_325/current/pdf.
- Lowry OH, Rosenbrough NJ, Farr AL (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
- Ma JQ, Luo RZ, Jiang HX, Liu CM (2015) Quercitrin offers protection against brain injury in mice by inhibiting oxidative stress and inflammation. Food Funct. doi: 10.1039/c5fo00913h Google Scholar
- Mc Cauley PT, Washington IS (1983) Barium, bioavailability as the chloride, sulfate, or carbonate salt in the rat. Drug Chem Toxicol 6:209–217CrossRefGoogle Scholar
- Mehmetçik G, Ozdemirler G, Koçak-Toker N, Cevikbaş U, Uysal M (2008) Effect of pretreatment with artichoke extract on carbon tetrachloride-induced liver injury and oxidative stress. Exp Toxicol Pathol 60:475–480CrossRefGoogle Scholar
- Mousavinejad G, Emam-Diomeh Z, Rezaei K, Khodaparast MHH (2009) Identification and quantification of phenolic compounds and their effects on antioxidant activity in pomegranate juices of eight Iranian cultivars. Food Chem 115:1274–1278CrossRefGoogle Scholar
- Nkozi CZ, Opoku AR, Terblanche SE (2005) Effect of pumpkin seed (Cucurbita pepo) protein isolate on the activity levels of certain plasma enzymes in CCl4-induced liver injury in low protein fed rats. Phytother Res 19:341–345CrossRefGoogle Scholar
- Ou P, Wolff SP (1996) A discontinuous method for catalase determination at near physiological concentrations of H2O2 and its application to the study of H2O2 fluxes within cells. J Biochem Biophys Methods 31:59–67CrossRefGoogle Scholar
- Petrovic S, Ozretic B, Krajnovic-Ozretic M, Bobinac D (2001) Lysosomal membrane stability and metallothioneins in digestive gland of mussels (Mytilus galloprovincialis Lam.) as biomarkers in a field study. Mar Pollut Bull 42:1373–1378CrossRefGoogle Scholar
- Pradeep K, Mohan CVR, Gobianand K, Karthikeyan S (2007) Effect of Cassia fistula Linn. Leaf extract on diethylnitrosamine induced hepatic injury in rats. Chem Biol Interact 167:12–18CrossRefGoogle Scholar
- Purdey M (2004) Chronic barium intoxication disrupts sulphated proteoglycan synthesis: a hypothesis for the origins of multiple sclerosis. Med Hypotheses 62:746–754CrossRefGoogle Scholar
- Ramachandran S, Asokkumar K, Uma Maheswari M, Ravi TK, Sivashanmugam AT, Saravanan S, Rajasekaran A, Dharman J (2011) Investigation of antidiabetic, antihyperlipidemic, and in vivo antioxidant properties of Sphaeranthus indicus Linn. in type 1 diabetic rats: an identification of possible biomarkers. Evid Based Complement Alternat Med. doi: 10.1155/2011/571721 Google Scholar
- Ramaiah SK, Jaeschke H (2007) Role of neutrophils in the pathogenesis of acute inflammatory liver injury. Toxicol Pathol 35:757–766CrossRefGoogle Scholar
- Rathmanner T, Kunze M, Rieder A (2004) Supplementation with mixed fruit and vegetable juice concentrates increased serum antioxidants and folate in healthy adults. J Am Coll Nutr 23:205–211CrossRefGoogle Scholar
- Renugadevi J, Milton Prabu S (2010) Cadmium induced hepatotoxicity in rats and the protective effect of Naringenin. Exp Toxicol Pathol 62:171–181CrossRefGoogle Scholar
- Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, Faggioni R, Luini W, van Hinsbergh V, Sozzani S, Bussolino F, Poli V, Ciliberto G, Mantovani A (1997) Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 6:315–325CrossRefGoogle Scholar
- Seeram NP, Aronson WJ, Zhang Y, Henning SM, Moro A, Lee RP, Sartippour M, Harris DM, Rettig M, Suchard MA, Pantuck AJ, Belldegrun A, Heber D (2007) Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland. J Agric Food Chem 55:7732–7737CrossRefGoogle Scholar
- Shaban NZ, El-Kersh MA, El-Rashidy FH, Habashy NH (2013) Protective role of Punica granatum (pomegranate) peel and seed oil extracts on diethylnitrosamine and phenobarbital-induced hepatic injury in male rats. Food Chem 14:1587–1596CrossRefGoogle Scholar
- Sohal RS, Brunk UT (1992) Mitochondrial production of pro-oxidants and cellular senescence. Mutat Res 275(3-6):295–304CrossRefGoogle Scholar
- Soudani N, Ben Amara I, Sefi M, Boudawara T, Zeghal N (2011) Effects of selenium on chromium (VI)-induced hepatotoxicity in adult rats. Exp Toxicol Pathol 63:541–548CrossRefGoogle Scholar
- Stanikunaite R, Khan SI, Trappe JM, Ross SA (2009) Cyclooxygenase-2 inhibitory and antioxidant compounds from the truffle Elaphomyces granulatus. Phytother Res 23:575–578CrossRefGoogle Scholar
- Storz P, Döppler H, Toker A (2005) Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species. Mol Cell Biol 25:8520–8530CrossRefGoogle Scholar
- Tardiff RG, Robinson M, Ulmer NS (1980) Subchronic oral toxicity of BaCl2 in rats. J Environ Pathol Toxicol 4:267–275Google Scholar
- Valkova M (2002) Hepatic fibrogenosis. Bratisl Lek Listy 103:76–85Google Scholar
- Viarengo A, Ponzano E, Dondero F, Fabbri R (1997) A simple spectrophotometric method for metallothionein evaluation in marine organisms: an application to Mediterranean and Antarctic mollusks. Mar Environ Res 44:69–84CrossRefGoogle Scholar
- Wang Y, Fang J, Leonard SS, Rao KM (2004) Cadmium inhibits the electron transfer chain and induces reactive oxygen species. Free Radic Biol Med 36:1434–1443CrossRefGoogle Scholar
- WHO (World Health Organization), Barium and barium compounds. CICAD 33, Geneva, Switzerland (2001) Available from: <http://whqlibdoc.who.int/publications/2001/9241530332.pdf>.
- Witko V, Nguyen AT, Descamps-Latscha B (1992) Microtiter plate assay for phagocyte-derived taurine chloramines. J Clin Lab Anal 6:47–53CrossRefGoogle Scholar