Beneficial effects of Pimpinella anisum L. ethanol and aqueous extracts on L-asparaginase-associated hepatotoxicity using specific 99mTc-Phytate biodistribution studies in rats

authors:

avatar Somayeh Shahani , avatar Meisam Sahranavard , avatar Fereshteh Amiri , avatar Seyed Mohammad Abedi , avatar Zohreh Noaparast , *


how to cite: Shahani S, Sahranavard M, Amiri F, Abedi S M, Noaparast Z. Beneficial effects of Pimpinella anisum L. ethanol and aqueous extracts on L-asparaginase-associated hepatotoxicity using specific 99mTc-Phytate biodistribution studies in rats. koomesh. 2024;24(4):e152765. 

Abstract

Introduction: The present study aimed to investigate the protective effects of Pimpinella anisum L. ethanolic and aqueous extracts on L-asparaginase- associated hepatotoxicity in rats using histopathological and specific 99mTc-Phytate biodistribution studies. Materials and Methods: 60 female rats were divided into 9 treatment groups including L-asparaginase group, Aqueous extract (100 and 200 mg/kg), Ethanolic extract (100 and 200 mg/kg), Aqueous extract (100 mg/kg) + L-asparaginase, Aqueous extract (200 mg/kg) + L-asparaginase, Ethanolic extract (100-100 mg/kg) + L-asparaginase, and Ethanolic extract (200 mg/kg) + L-asparaginase and one control group. L-asparaginase was intraperitoneally injected at a dose of 1000 IU/Kg every other day for a week. Aqueous and ethanolic extracts of P. anisum were given by gavage technique for seven consecutive days. 24h after the last day of treatment, 99mTc-phytate was intravenously injected and then, rats were killed with a lethal dose of ketamine/xylazine. Vital organs were removed, weighed, and their activity was counted by a gamma counter. 99mTc-phytate scintigraphy and histopathological assessment were performed for further evaluation. Results: L-asparaginase-induced liver toxicity was significantly reduced with ethanolic extract in L-asparaginase-treated rats (P˂0.05). It is worth mentioning that the aqueous extract of Anise seed led to hepatotoxicity (P˂0.05) which is likely to be mainly due to contamination of the plant with the toxic pyrrolizidine alkaloids. Conclusion: P. anisum ethanolic extract due to the presence of anethole and phenolic compounds can ameliorate L-asparaginase-induced hepatotoxicity in rats.

References

  • 1.

    Inaba H, Greaves M, Mullighan ChG. Acute lymphoblastic leukaemia. Lancet 2013; 381: 1943-1955.https://doi.org/10.1016/S0140-6736(12)62187-4.

  • 2.

    Jabbour E, Thomas D, Cortes J, Kantarjian HM, O'Brien S. Central nervous system prophylaxis in adults with acute lymphoblastic leukemia: current and emerging therapies. Cancer 2010; 116: 2290-2300.https://doi.org/10.1002/cncr.25008PMid:20209620.

  • 3.

    Kondrat'eva NA, Kruglova GV, Lorie IuI, Koshel IV, Kurmashov VI. [L-asparaginase study results (phase II of the clinical trials)]. Antibiotiki 1980; 25: 686-689.

  • 4.

    King PD, Perry MC. Hepatotoxicity of chemotherapy. Oncologist 2001; 6: 162-176.https://doi.org/10.1634/theoncologist.6-2-162PMid:11306728.

  • 5.

    Thatishetty AV, Agresti N, O'Brien ChB. Chemotherapy-Induced Hepatotoxicity. Clin Liver Dis 2013; 17: 671-686.https://doi.org/10.1016/j.cld.2013.07.010PMid:24099024.

  • 6.

    Kapoor S. Ursodeoxycholic acid and its emerging role in attenuation of tumor growth in gastrointestinal malignancies. J Cachexia Sarcopenia Muscle 2012; 3: 277-278.https://doi.org/10.1007/s13539-012-0091-5PMid:23150116 PMCid:PMC3505581.

  • 7.

    Adesanoye OA, Farombi EO. Hepatoprotective effects of Vernonia amygdalina (astereaceae) in rats treated with carbon tetrachloride. Exp Toxicol Pathol 2010; 62: 197-206.https://doi.org/10.1016/j.etp.2009.05.008PMid:19581077.

  • 8.

    Shehab NG, Abu-Gharbieh E, Bayoumi FA. Impact of phenolic composition on hepatoprotective and antioxidant effects of four desert medicinal plants. BMC Complement Altern Med 2015; 15: 401-413.https://doi.org/10.1186/s12906-015-0919-6PMid:26552870 PMCid:PMC4640355.

  • 9.

    Taslidere E, Dogan, Z, Elbe H, Vardi N, Cetin A, Turkoz Y. Quercetin protection against ciprofloxacin induced liver damage in rats. Biotech Histochem 2015; 91: 116-121.https://doi.org/10.3109/10520295.2015.1085093PMid:26529398.

  • 10.

    Pourgholami MH, Majzoob S, Javadi M, Kamalinejad M, Fanaee GH, Sayyah M. The fruit essential oil of Pimpinella anisum exerts anticonvulsant effects in mice. J Ethnopharmacol 1999; 66: 211-215.https://doi.org/10.1016/S0378-8741(98)00161-5.

  • 11.

    Tabanca N, Ma G, Pasco DS, Bedir E, Kirimer N, Baser KHC, et al. Effect of essential oils and isolated compounds from Pimpinella species on NF-kappaB: a target for antiinflammatory therapy. Phytother Res 2007; 21: 741-745.https://doi.org/10.1002/ptr.2154PMid:17450505.

  • 12.

    Gln I, Oktay M, Krec E, Kfrevolu . Screening of antioxidant and antimicrobial activities of anise (Pimpinella anisum L.) seed extracts. Food Chem 2003; 83: 371-382.https://doi.org/10.1016/S0308-8146(03)00098-0.

  • 13.

    Al-Ismail Kh, Aburjai T. Antioxidant activity of water and alcohol extracts of chamomile flowers, anise seeds and dill seeds. J Sci Food Agricul 2004; 84: 173-178.https://doi.org/10.1002/jsfa.1625.

  • 14.

    Tirapelli CR, de Andrade CR, Cassano AO, De Souza FA, Ambrosio SR, da Costa FB, de Oliveira AM. Antispasmodic and relaxant effects of the hidroalcoholic extract of Pimpinella anisum (Apiaceae) on rat anococcygeus smooth muscle. J Ethnopharmacology 2007; 110: 23-29.https://doi.org/10.1016/j.jep.2006.08.031PMid:17027208.

  • 15.

    Singh G, Kapoor IPS, Singh P, de Heluani CS, Catalan CA. Chemical composition and antioxidant potential of essential oil and oleoresins from anise seeds (Pimpinella anisum L.). Int J Essent Oil Therap 2008; 2: 122-130. http://hdl.handle.net/11336/61242.

  • 16.

    Abdelaaty ASh, Ibrahim AY, Hendawy SF, Omer EA, Hammouda FM, Abdel-Rahman FH, Saleh MA. Chemical composition, antimicrobial and antioxidant activities of essential oils from organically cultivated fennel cultivars. Molecules 2011; 16: 1366-1377.https://doi.org/10.3390/molecules16021366PMid:21285921 PMCid:PMC6259638.

  • 17.

    El-Sayed MG, Elkomy A., Samer S, Elbanna AH. Hepatoprotective effect of Pimpinella anisum and Foeniculim vulgare against Carbon Tetra Chloride Induced Fibrosis in Rats. World J Pharm Pharm Sci 2015; 4: 78-88.

  • 18.

    Kikuchi M, Tomita K, Nakahara T, Kitamura N, Teratani T, Irie R, et al. Utility of quantitative 99mTc-phytate scintigraphy to diagnose early-stage non-alcoholic steatohepatitis. Scand J Gastroenterol 2009; 44: 229-236.https://doi.org/10.1080/00365520802433249PMid:18819037.

  • 19.

    Miliauskas G, Venskutonis RP, Van Beek TA. Screening of radical scavenging activity of some medicinal and aromatic plant extracts. Food Chem 2004; 85: 231-237.https://doi.org/10.1016/j.foodchem.2003.05.007.

  • 20.

    Da Silva MC, Paiva SR. Antioxidant activity and flavonoid content of Clusia fluminensis Planch. & Triana. An Acad Bras Cienc 2012; 84: 609-616.https://doi.org/10.1590/S0001-37652012000300004PMid:22886157.

  • 21.

    Roesmann A, Afify M, Panse J, Eisert A, Steitz J, Tolba RH. L-carnitine ameliorates L-asparaginase-induced acute liver toxicity in steatotic rat livers. Chemotherapy 2013; 59: 167-175.https://doi.org/10.1159/000353402PMid:24192517.

  • 22.

    Celle G, Dodero M, Pannacciulli I. The liver damaging effect of L-asparaginase-An experimental study of chronic toxicity. Eur J Cancer 1973; 9: 55-57.https://doi.org/10.1016/0014-2964(73)90043-1.

  • 23.

    Sahoo S, Hart J. Histopathological features of L-asparaginase-induced liver disease. Semin Liver Dis 2003; 23: 295-300.https://doi.org/10.1055/s-2003-42647PMid:14523682.

  • 24.

    Haskell C, Canellos GP, Leventhal BG, Carbone PP, Serpick AA, Hansen HH. L-asparaginase toxicity. Cancer Res 1969; 29: 974-975.

  • 25.

    Roudsarabi E, Kazemi Noureini S, Faridnouri H, Vaezi Kakhki MR. Effects of methanolic extracts of Epilobium parviflorum on growth and function of human liver cells HepG2. Koomesh 2021, 23: 801-812. (Persian).

  • 26.

    Rebey IB, Wannes WA, Kaab SB, Bourgou S, Tounsi MS, Ksouri R, Fauconnier ML. Bioactive compounds and antioxidant activity of Pimpinella anisum L. accessions at different ripening stages. Scient Horticul 2019; 246: 453-461.https://doi.org/10.1016/j.scienta.2018.11.016.

  • 27.

    Wagner H, Bladt S. Plant drug analysis: a thin layer chromatography atlas. 2nd Edition, Springer Science & Business Media. 1996.https://doi.org/10.1007/978-3-642-00574-9.

  • 28.

    Martins N, Barros L, Santos-Buelga C, Ferreira IC. Antioxidant potential of two Apiaceae plant extracts: A comparative study focused on the phenolic composition. Indust Crops Product 2016; 79: 188-194.https://doi.org/10.1016/j.indcrop.2015.11.018.

  • 29.

    Souri E, Amin G, Farsam H. Screening of antioxidant activity and phenolic content of 24 medicinal plant extracts. DARU J Pharm Sci 2008; 16: 83-87.

  • 30.

    Marques V, Farah A. Chlorogenic acids and related compounds in medicinal plants and infusions. Food Chem 2009; 113: 1370-1376.https://doi.org/10.1016/j.foodchem.2008.08.086.

  • 31.

    Chen Z, Yang Y, Mi S, Fan Q, Sun X, Deng B, et al. Hepatoprotective effect of chlorogenic acid against chronic liver injury in inflammatory rats. J Funct Food 2019; 62: 103540.https://doi.org/10.1016/j.jff.2019.103540.

  • 32.

    Sun ZX, Liu S, Zhao ZQ, Su RQ. Protective effect of chlorogenic acid against carbon tetrachloride-induced acute liver damage in rats. Chin Herbal Med 2014; 6: 36-41.https://doi.org/10.1016/S1674-6384(14)60004-6.

  • 33.

    Jamshidzadeh A, Heidari R, Razmjou M, Karimi F, Moein MR, Farshad O, et al. An in vivo and in vitro investigation on hepatoprotective effects of Pimpinella anisum seed essential oil and extracts against carbon tetrachloride-induced toxicity. Iran J Basic Med Sci 2015; 18: 205-211.

  • 34.

    Mennecozzi M, Landesmann B, Palosaari T, Harris G, Whelan M. Sex differences in liver toxicity-do female and male human primary hepatocytes react differently to toxicants in vitro. PloS One 2015; 10: e0122786.https://doi.org/10.1371/journal.pone.0122786PMid:25849576 PMCid:PMC4388670.

  • 35.

    Koriem KM. Approach to pharmacological and clinical applications of Anisi aetheroleum. Asian Pac J Tropical Biomed 2015; 5: 60-67.https://doi.org/10.1016/S2221-1691(15)30172-6.

  • 36.

    Radzikowska E, Luszczewska-Sierakowska I, Madej B, Burdan F, Mandziuk S, Sokoluk M, et al. Estrogen-induced hepatotoxicity in rats. J Pre-Clin Clin Res 2012; 6: 10-13.

  • 37.

    Vasil'ev ED, Il'nitskaia SI, Nikitenko EV, Kaledin VI. Age-and sex-related differences in sensitivity to hepatotoxic action of estragole in mice. Ross Fiziol Zh Im I M Sechenova 2005; 91: 1066-1070.

  • 38.

    Wang X, Lou YJ, Wang MX, Shi YW, Xu HX, Kong LD. Furocoumarins affect hepatic cytochrome P450 and renal organic ion transporters in mice. Toxicol Lett 2012; 209: 67-77.https://doi.org/10.1016/j.toxlet.2011.11.030PMid:22173200.

  • 39.

    Oler A, Neal MW, Mitchell EK. Tannic acid: acute hepatotoxicity following administration by feeding tube. Food Cosmetic Toxicol 1976; 14: 565-569.https://doi.org/10.1016/S0015-6264(76)80010-7.

  • 40.

    Bodi D, Ronczka S, Gottschalk C, Behr N, Skibba A, Wagner M, et al. These A. Determination of pyrrolizidine alkaloids in tea, herbal drugs and honey. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2014; 31: 1886-1895.https://doi.org/10.1080/19440049.2014.964337PMid:25222912.

  • 41.

    Schramm S, Khler N, Rozhon W. Pyrrolizidine alkaloids: biosynthesis, biological activities and occurrence in crop plants. Molecules 2019; 24: 498.https://doi.org/10.3390/molecules24030498PMid:30704105 PMCid:PMC6385001.

  • 42.

    Kisielius V, Hama JR, Skrbic N, Hansen HC, Strobel BW, Rasmussen LH. The invasive butterbur contaminates stream and seepage water in groundwater wells with toxic pyrrolizidine alkaloids. Sci Rep 2020; 10: 1-10.https://doi.org/10.1038/s41598-020-76586-1PMid:33188248 PMCid:PMC7666219.

  • 43.

    Yang M, Ma J, Ruan J, Ye Y, Fu PP, Lin G. Intestinal and hepatic biotransformation of pyrrolizidine alkaloid N-oxides to toxic pyrrolizidine alkaloids. Arch Toxicol 2019; 93: 2197-2209.https://doi.org/10.1007/s00204-019-02499-2PMid:31222523.