Apium Graveolens and Rosmarinus Officinalis Protect from Liver Toxicity Induced by Sodium Valproate in Rats and Potentiate its Anticonvulsant Activity on Pentylenetetrazol-Treated Rats
Keywords:
Sodium valproate, liver toxicity, protection, Apium gravuonalues, Rosmarinus officinalis, Liver toxicity, Apium Graveolens, Rosmarinus Officinalis, Anticonvulsant activity.Abstract
Hepatic injury is a dose-limiting side effect of sodium valproate (VPA), a common used drug in the management of numerous nurological disorders, including epilepsy. The present study was designed to investigate the effect of Apium Grafionalies (AG) and Rosmarinus officinalis (RO) against VPA-induced liver injury. Hepatic toxicity was induced by the administration of VPA (500 mg/kg/day) once daily for a period of 7 days. The hepatoprotective group received ethanolic extracts of AG and RO (200 mg/kg/day) for 7 days prior to VPA treatment for seven days. VPA liver toxicity was evaluated based on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and, albumin, and total protein levels as well as by histology. Serum ALT and AST activities were elevated and albumin and total protein levels were depleted. Histopathological changes in liver such as fatty degeneration and focal necrosis were associated with significant increase in TUNEL-positive cells and P53 protein in immunohistochemical study indicating the presence of DNA fragmentation.
This biochemical and histological changes were associated with increased oxidative stress damage as evidenced by increases in protein carbonyl (P.Carbonyl) and decreases in total antioxidant capacity (TAC) in liver. These biochemical and histological disturbances were effectively attenuated on pretreatment with either AG or RO extract, which normalized P.Carbonyl and TAC and attenuated histopathological changes induced by VPA. These observations shed light on the hepatoprotective actions of both AG and RO extracts against experimental VPA toxicity. AG was characterized for its apigenin content while RO was characterized for its rosmarinic acid and carnazol contents. Besides, in a pentylenetetrazole (PTZ) rat clonic convulsion model, pretreatment with AG and RO (200 mg/kg) before VPA protected against PTZ-induced convulsion, where it delayed the onset of clonic convulsion in PTZ treated rats.
References
D.C. Lagace, W.T. O
K. Sato, Y. Ueda, K. Ueno, K. Okamoto, H. Iizuka, S. Katsuda, Hepatocellular carcinoma and nonalcoholic steatohepatitis developing during long-term administration of valproic acid, Virchows Archiv, 447 (2005) 996-999.
A. Verrotti, G. Di Marco, R. La Torre, P. Pelliccia, F. Chiarelli, Nonalcoholic fatty liver disease during valproate therapy, European journal of pediatrics, 168 (2009) 1391-1394.
K. Begriche, J. Massart, M.-A. Robin, A. Borgne-Sanchez, B. Fromenty Drug-induced toxicity on mitochondria and lipid metabolism: mechanistic diversity and deleterious consequences for the liver. , Journal of hepatology, 54 (2011) 773-794.
J. Pourahmad, M.R. Eskandari, M. Kaghazi, F. Shaki, F. Shahraki, J.K. Fard, A new approach on valproic acid induced hepatotoxicity: Involvement of lysosomal membrane leakiness and cellular proteolysis. , Toxicology in Vitro 26 (2012) 545
V. Tong, X.W. Teng, T.K. Chang, F.S. Abbott, Valproic acid I: Time course of lipid peroxidation biomarkers,liver toxicity, and valproic acid metabolite level in rats, Toxicol. Sci, 86 (2005) 427-435.
B.B. Sokmen, S. Tunali, R. Yanardag, Effects of vitamin U (S-methyl methionine sulphonium chloride) on valproic acid induced liver injury in rats, Food and Chemical Toxicology, 50 (2012) 3562
M.A. Abdel-Dayem, A.A. Elmarakby, A.A. Abdel-Aziz , C. Pye, S.A. Said, A.M. El-Mowafy, Valproate-Induced Liver Injury: Modulation by the Omega-3nFatty Acid DHA Proposes a Novel Anticonvulsant Regimen., Drugs R D, (2014).
A.A. Hamza, F. El Hodairy, A.M. Badawi, Safranal ameliorates sodium valproate-induced liver toxicity in rats by targeting gene expression, oxidative stress and apoptosis, Journal of Biomedical and Pharmaceutical Research, 4 (2015) 46-60.
K.H. Schulpis, C. Lazaropoulou, S. Regoutas, G.A. Karikas, A. Margeli, S. Tsakiris, I. Papassotiriou, Valproic acid monotherapy induces DNA oxidative damage, Toxicology 217 (2006) 228
U. Yi?, E. Se
M. Jurima-romet, F.S. Abbott, W. Tang, H.G. Huang, Cytotoxicity of unsaturated metabolites of valproic acid and protection by vitamins C and E in glutathione-depleted rat hepatocytes. , Toxicology, 112 (1996) 69-85.
I.L. Bykov, t. Mal, A.N., V.A. Gurinovich, L.I. Nefedov, Biochemical basis of valproic acid toxicity:role of oxidative stress and effects of L-carnitine, Biomed.Khim., 50 (2004) 384-389.
G.Q. Zheng, P.M. Kenney, J. Zhang, L.K. Lam, Chemoprevention of benzo (a) pyrene-induced forestomach cancer in mice by natural phthalides from celery seed oil, Nutrat. Cancer, 19 (1993) 77-86.
J. Kitajima, T. Ishikawa, M. Satoh, Polar constituents of celery. , Phytochemistry, 64 (2003) 1003-1011.
S. Sultana, A. Salahuddin, J. Tamanna, S. Sharma, Inhibitory effect of celery seed extract on chemically induced hepatocarcinogenesis:modulation of cell proliferation, metabolism and altered hepatic foci development. , Cancer lett., 221 (2005) 11-20.
H. Haraguchi, T. Saito, N. Okamura, A. Yagi, Inhibition of lipid peroxidation and superoxide generation by diterpenoids fron Rosemarinus officinalis., Planta . Med., 61 (1995) 333-336.
H.H. Zeng, P.F. Tu, K. Zhou, H. Wang, B.H. Wang, J.F. Lu, Antioxidant properties of phenolic diterpenes from Rosmarinus officinalis., Acta Pharmacol.Sin., 22 (2001) 1094-1098.
E. Ibanez, A. Kubatova, F.J. Senorans, S. Cavero, G. Reglero, Subcritical water extraction of antioxidant compounds from rosemary plants., J.Agric.Food Chem., 51 (2003) 375-382.
S. Munne-Bosch, K. Schwarz, L. Alegre, Enhanced Formation of alpha-Tecopherol and highly oxidixed Abietane diterpenes in Water-Stressed Rosemary, Plants, 121 (1999) 1047-1052.
G.V. Satyavati, M.K. Raina, Medicinal Plants of Indi, Indian Council of Medical Research.New Delhi, India, 1976.
R.A. Momin, M.G. Nair, Antioxidant, cyclooxygenase and topoisomerase inhibitory compounds from Apium graveolens Linn.seeds. , Phytomedicine, 9 ( 2002) 312-318.
J.a. Jeyabalan, F.b. Aqil, L.a. Soper, D.J.c. Schultz, R.C. Gupta, Potent Chemopreventive/Antioxidant Activity Detected in Common Spices of the Apiaceae Family Nutrition and Cancer, 67 (2015) 1201-1207.
A. Singh, S.S. Handa, Hepatoprotective activity of Apium graveolens and Hygrophila auriculata against paracetamol and thioacetamide intoxication in rats., J. Ethnopharmacol., 49 (1995) 119-126.
B. Ahmed, T. Alam, M. Varshney, S.A. Khan, Hepatoprotective activity of two plants belonging to the Apiaceae and the Euphorbiaceae family., J. Ethnopharmacol., 79 ( 2002) 313-316.
D. Tsi, B.K.H. Tan, Lipid-lowering activity of aqueous celery extract and its fractions in hypercholesterolaemic rats and mice., Med. Sc.i Res.,, 25 (1997) 673-675.
M. Whitehouse, D. Butters, M. Clarke, K. Rainsford, NSAID gastropathy: prevention by celery seed extracts in disease-stressed rats, Inflammopharmacology, 9 (2001) 201-209.
T. Aydemir , S. Becerik, Phenolic content and antioxidant activity of different extracts from Ocimum basilicum, Apium graveolens and Lepidium sativum seeds., Journal of Food Biochemistry 35 (2011) 62-79.
A.A. Hamza, A. Amin, Apium graveolens modulates sodium valproate-Induced reproductive toxicity in rats, Journal of Experimental Zoology 307A (2007) 199
F. Fahim, A. Esmat, H. Fadel, K. Hassan, Allied studies on the effect of Rosemarinus officinalis L.on experimental hepatotoxicity and mutagenesis. , Int.J.Food.Sci.Nutr., 50 (1999) 413-427.
A. al-Hader, Z. Hasan, M. Aqel, Hyperglycemic and insulin release inhibitory effects of Rosmarinus officinalus., J. Ethnopharmacol., 43 (1994) 217-221.
P.C. Dias, M.A. Foglio, A. Possenti, J. Carvahlo, Antiucerogenic activity of crude hydroalcoholic extract of rosmarinus officinalis., J. Ethnopharmacol., 69 (2000) 57-62.
J.I. Sotelo-Felix, D. Martinez-Fong, P. Mureil De laTorre, Protective effect of carnosol on CCl(4)-induced acute liver damage in rats. , Eur. J. Gastroenterol.Hepatol., 14 (2002) 1001-1006.
B. Zegura, D. Dobnik, M.H. Niderl, M. Filipi, Antioxidant and antigenotoxic effects of rosemary (Rosmarinus officinalis L.) extracts in Salmonella typhimurium TA98 and HepG2 cells. , Environmental Toxicology and Pharmacology 32 (2011) 296
S.M. Petiwala, J.J. Johnson, Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity, Cancer letters, 367 (2015) 93-102.
A.-V. Ferlemi, A. Katsikoudi, V.G. Kontogianni, T.F. Kellici, G. Iatrou, F.N. Lamari, A.G. Tzakos, M. Margarity, Rosemary tea consumption results to anxiolytic-and anti-depressant-like behavior of adult male mice and inhibits all cerebral area and liver cholinesterase activity; phytochemical investigation and in silico studies, Chemico-biological interactions, 237 (2015) 47-57.
M. Joyeux, A. Roland, J. Fleurentier, F. Mortier, P. Dorfman, Tert-Butyl hydroperoxide induced injury isolated rat hepatocytes: amodel for studying anti-hepatotoxoxic crude drugs., Planta . Med., 56 (1990) 171-174.
C. Hoefler, J. Fleurentier, F. Mortier, J. Pelt, J. Guillemain, Comparative choleretic and hepatoprotective properties of young sprouts and total plant extracts of Rosemarinus officinalis in rats., J. Ethnopharmacol., 19 (1987) 133-143.
A. Ra
A. Amin, A.A. Hamza, Hepatoprotective effects of Hibiscus, Rosmarinus and Salvia on azathioprine-induced toxicity in rats Life Sciences, 77 (2005) 266
E. Olfert, B. Cross, A. Mc William, Canadian Council on Animal Care, Guide to the care and use of experimental animals. , (1993)
S.P. Wang, K.J. Huang, Determination of flavonoids by high-performance liquid chromatography and capillary electrophoresis. , J Chromatogr., 1032 (2004) 273-279.
H. Draper, A.N. Hadley, Malondialdehyde determination as index of lipid peroxidation., in: L. Packer, A. Glazer (Eds.) Method in enzymology, Academic press., 1990.
M. Uchiyama, M. Mihara, Determination of malonaldehyde precursor in tissues by thiobarbituric acid test., Anal. Biochem., 86 (1978) 271
I. Dalle-Donne, R. Rossi, D. Giustarini, A. Milzani, R. Colombo, Protein carbonyl groups as biomarkers of oxidative stress., Clin. Chim. Acta 329 (2003) 23
A.Z. Reznick, L. Packer, Oxidative damage to proteins: spectrophotometric method for carbonyl assay., Methods Enzymol. , 233- 375-363 (1994)
I.F. Benzie, J.J. Strain, The ferric reducing ability of plasma (FRAP) as a measure of (antioxidant power): the FRAP assay. , Anal. Biochem., 293 (1996) 70
G.L. Peterson, A simplification of the protein assay method of Lowry et al., which is more generally applicable., Anal. Biochem . 83 (1977) 346
B. Grasl-Kraupp, B. Ruttkay-Nedecky, H. Koudelka, K. Bukowska, W. Bursch, R. Schulte-Hermann, In situ detection of fragmented DNA (TUNEL assay) fails to disciminate among apoptosis, and autolytic cell death : a cautionary note. , Hepatology, 21 (1995) 1465-1468.
M. Gomez-Lazaro, F.J. Fernandez-Gomez, J. Jordan, P53:twenty five years understanding the mechanism of genome protection. , J.Physiol.Biochem., 60 (2004) 287-307.
D. Szoke, S.F. Spisak, B. Molnar, Z. Tulassay, The p53 gene and protein in 2005: new results, promising opportunities. , Orv.Hetil., 146 (2005 ) 1587-1594.
S. Peng, M. Zhao, Pharmaceutical bioassays: methods and applications, in, John Wiley & Sons, 2009, pp. 237- 248.
M.M. Safar, D.M. Abdallah, N.M. Arafa, M.T. Abdel-Aziz, Magnesium supplementation enhances the anticonvulsant potential of valproate in pentylenetetrazol-treated rats, Brain research, 1334 (2010) 58-64.
M. Sobaniec-Lotowska, W. Sobaniec, W. Kulak, Rat liver pathomorphology during prolonged sodium valproate administration. , Mater. Med.Pol., 25 (1993) 9-12.
E. Hauser, R. Seidl, M. Freilinger, C. Male, K. Herkner, Hematologic manifestations and impaired liver synthetic function during valproate monotherapy. , Brain Develop., 18 (1996) 105-109.
T.A. Rugino, Y.M. Janvier, J.M. Baunach, C.A. Bilat, Hypoalbuminemia with valproic acid administration. , Pediat.Neuro., 29 (2003) 440-444.
N.A. El-Shinnawy, The therapeutic applications of celery oil seed extract on the plasticizer di (2-ethylhexyl) phthalate toxicity, Toxicology and industrial health, 31 (2015) 355-366
F.M El-Demerdash, E.A. Abbady, H.H. Baghdadi, Oxidative stress modulation Rosmarinus officinalis in creosote?induced hepatotoxicity, Environmental toxicology, 31 (2014) 85-92.
J.P. Fruehauf, F.L. Meyskens, Reactive oxygen species: a breath of life or death?, Clinical Cancer Research, 13 (2007) 789-794.
M.G. Neuman, N.H. Shear, P.M. Jacobson-Brown, G.G. Katz, H.K. Neilson, I.M. Malkiewicz, R.G. Cameron, F. Abbott, CYP2E1-mediated modulation of valproic acid-induced hepatotoxicity., Clinic.Biochem., 34 (2001) 211-218.
A. Phillips, T. Bullock, N. Plant, Sodium valproate induces apoptosis in the rats hepatoma cell line, FaO., Toxicology, 192 (2003) 219-227.
R.J. Steele, D.P. Lane, P53 in cancer: a paradigm for modern management of cancer, Surgeon,, 3 (2005) 197-205.
D. Slame?ov
K. Razavi-Azarkhiavi, J. Behravan, F. Mosaffa, S. Sehatbakhsh, K. Shirani, G. Karimi, Protective effects of aqueous and ethanol extracts of rosemary on H2O2-induced oxidative DNA damage in human lymphocytes by comet assay, Journal of Complementary and Integrative Medicine, 11 (2014) 27-33.
I. Borr
K.H. Miean, S. Mohammed, Flavonoid ( myricetin, Quercetin, Kaempferol, luteolin, and apigenin) content of edible tropical plants. , J. Agri. Food Chem., 49 (2001) 3106-3112.
G.P. Amaral, N.R. de Carvalho, R.P. Barcelos, F. Dobrachinski, R. de Lima Portella, M.H. da Silva, T.H. Lugokenski, G.R.M. Dias, S.C.A. da Luz, A.A. Boligon, Protective action of ethanolic extract of Rosmarinus officinalis L. in gastric ulcer prevention induced by ethanol in rats, Food and Chemical Toxicology, 55 (2013) 48-55.
V. Jakovljevic, A. Raskovic, M. Popovic, J. Sabo, The effect of celery and parsley juices on pharmacodynamic activity of drugs involving cytochrome P450 in their metabolism. , Eur. J. Drug Merab.Pharmacokinet, 27 (2002) 153-156.
P. Debersac, M.F. Verneva, M.J. amiot, M. Suschetet, M.-H. Siess, Effect of awater soluble extract of rosemary and its purified component rosemarinic acid on xenobiotic-metabolizing enzymes in rat liver. , Food .Chem. Toxicol, 3 117-109 (2001).
Downloads
Published
How to Cite
Issue
Section
License
Authors who submit papers with this journal agree to the following terms.
