Physiological and histological effects of apigenin and luteolin on Cytarabine injected rats
Main Article Content
Abstract
The present study was undertaken to study the effect of apigenin and luteolin on physiological and histological changes in rats treated with cytarabine drugs. Thirty-five albino healthy male adult rats with equal age weighing 250 -300g were enrolled. Rats were randomly divided into seven groups according to the treatment. Group “1” was treated with normal saline and served as the control group. Groups “2,3 and 4” received cytarabine, apigenin, and luteolin respectively, while groups 5, 6, and 7 received a combination of “apigenin + cytarabine”, “luteolin + cytarabine”, and “apigenin + luteolin + cytarabine”, respectively. After one week of treatment, all seven groups of rats were sacrificed for histological finding, and blood samples were collected from each rat for biochemical parameters analysis. The results of this study showed that cytarabine increased the activity of GPT, GOT, and cholesterol levels in rats after one week of intraperitoneal injection in comparison to the control. There was no significant difference in GPT and GOT when apigenin and luteolin were administrated orally compared to the control group. When apigenin and luteolin are combined with cytarabine, they have a protective effect on leakage of liver enzymes GPT and GOT in serum. Apigenin and luteolin histologically protect liver cells from cytarabine damage when administered alone. These findings conclude that apigenin and luteolin have a protective effect on cytarabine side effects on the liver and its function in rats.
Received 2/2/2022
Revised 28/11/2022
Accepted 30/11/2022
Published Online First 20/5/2023
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
How to Cite
References
Ramesh G, Reeves WB . Salicylate reduces cisplatin nephrotoxicity by inhibition of tumor necrosis factor-alpha. Kidney Int. 2004; 65:490–499. https://doi.org/10.1111/j.1523-1755.2004.00413.x.
Morimoto Y, Baba T, Sasaki T, Hiramatsu K. Apigenin as an antiquinolone- resistance antibiotic. Int J Antimicrob Agents 2015; 46: 666–673. https://doi.org/10.1016/j.ijantimicag.2015.09.006.
Patil RH, Babu RL, Naveen Kumar M, Kiran Kumar KM, Hegde SM, Nagesh R, et al.Anti-inflammatory effect of apigenin on LPS-induced pro-inflammatory mediators and AP-1 factors in human lung epithelial cells. Inflammation 2016; 39: 138–147. https://doi.org/10.1007/s10753-015-0232-z.
Shibata C, Ohno M, Otsuka M, Kishikawa T, Goto K, Muroyama R, et al . The flavonoid apigenin inhibits hepatitis C virus replication by decreasing mature microRNA122 levels. Virology 2014; 462–463: 42–48. https://doi.org/10.1016/j.virol.2014.05.024.
Zhang W, Qiao H, Lv Y, Wang J, Chen X, Hou Y, et al . Apigenin inhibits enterovirus-71 infection by disrupting viral RNA association with trans-acting factors. PLoS One 2014; 9: e110429. https://doi.org/10.1371/journal.pone.0110429.
Zhou RJ, Ye H, Wang F, Wang JL, Xie ML. Apigenin inhibits d-galactosamine/LPS-induced liver injury through upregulation of hepatic Nrf-2 and PPARγ expressions in mice. Biochem Biophys Res Commun 2017; 493(1), 625-630. https://doi.org/10.1016/j.bbrc.2017.08.141.
Papay ZE, Kosa A, Boddi B, Merchant Z, Saleem IY, Zariwala MG, et al . Study on the pulmonary delivery systemof apigenin-loaded albumin nanocarriers with antioxidant activity. J Aerosol Med Pulm Drug Deliv. 2017; 30: 274–88. https://doi.org/10.1089/jamp.2016.1316.
Galbiatti AL, Padovani-Junior JA, Maníglia JV, Rodrigues CD, Pavarino ÉC, Goloni-Bertollo EM. Head and neck cancer: causes, prevention and treatment. Braz J Otorhinolaryngol. 2013; 79, 239-247. https://doi.org/10.5935/1808-8694.20130041.
Imran M, Rauf A, Abu-Izneid T, Nadeem M, Shariati MA, Khan IA, et al . Luteolin, a flavonoid, as an anticancer agent: A review Biomed. Pharmacother. 2019; 112, 108612. https://doi.org/10.1016/j.biopha.2019.108612.
Xiao Z, Zhuang B, Zhang G, Li M, & Jin Y. Pulmonary delivery of cationic liposomal hydroxycamptothecin and 5-aminolevulinic acid for chemo-sonodynamic therapy of metastatic lung cancerInt . J Pharm X. 2021; 601: 120572. https://doi.org/10.1016/j.ijpharm.2021.120572.
Benjimen, K., Thejomoorthy, K., Prasanna, P. S. Development and validation of new analytical method for the simultaneous estimation of daunorubicin and cytarabine in bulk and pharmaceutical dosage form. World J Curr Med Pharm Res. 2021; 32-39. https://doi.org/10.37022/wjcmpr.vi.171.
Fram RJ, Kufe DW. Inhibition of DNA excision repair and the repair of X-ray-induced DNA damage by cytosine arabinoside and hydroxyurea. Pharmacol Ther. 1985; 31(3): 165-176. https://doi.org/10.1016/0163-7258(85)90021-X.
EL-Shorbgi AN, Chaudhary S, Aljard AA, Omer E , Mahmoud F, Gupta RK., et al . Antineoplastic Marine Secondary Metabolites: Drugs, Drug-Candidates Under Clinical Trials, and Scaffolds of Potential Anticancer Activity. Int J Pharm Pharm Res. 2021; 15(2): 579-603.
Tsai HJ, Hsiao HH, Hsu YT, Liu YC, Kao HW, Liu TC, et al . Phase I study of ADI- PEG20 plus low- dose cytarabine for the treatment of acute myeloid leukemia. Cancer Med. 2021; 10: 2946–2955. https://doi.org/10.1002/cam4.3871.
Dawood Gh A, Taqa Gh A, Alnema MM. Histological Effect of Cytarabine on Liver and Buccal Mucosa in Mice. Rafidain Dent J. 2020 ;20 (1):36-45. http://dx.doi.org/10.33899/rden.2020.164521
Al-Helaly LA, Mahmood ES. Biochemical and Histological Study of Aminoacylase-1 Purified from Amniotic Fluid in Rats with Oxidative Stress Induced by Lead Acetate. Baghdad Sci J. 2021; 18(3): 583-592. https://doi.org/10.21123/bsj.2021.18.3.0583.
Hafkenscheid JCM, Dijt CCM. Determination of serum aminotransferases: activation by pyridoxal-5′-phosphate in relation to substrate concentration. Clin Chem. 1979; 25: 55–59. https://doi.org/10.1093/clinchem/25.1.55.
Purcell GV, Behenna DB, Walsh PR. Alanine aminotransferase and aspartate aminotransferase measurements with two automated analyzers, SMAC and the ABA-100, Compared. Clin.Chem. 1979; 25:780–782. https://doi.org/10.1093/clinchem/25.5.780.
Ibrahem RT, Mahmmod AM, Taqa GA. The protective and Antioxidant Effect of Catechin and Apigenin on Some Biochemical Parameters in Blood Serum of Rats Exposed to Oxidative Stress Induced by H2O2. Coll Bas Edu Res J. 2020 ; 16 (3) : 813-852. Doi: https://doi.org/10.33899/berj.2020.166002.
Weßels I, Rolles B, Slusarenko AJ, Rink L. Zinc deficiency as a possible risk factor for increased susceptibility and severe progression of COVID-19. Br J Nutr . 2021; 1-42. https://doi.org/10.1017/S0007114521000738.
Ibrahem RT, Mahmmod AM, Taqa GA. Synthesis of Silver Nano particles Using Catechin and Apigenin and Study their Anti- oxidant Effect on the Laboratory Rats. Coll Bas Edu Res J. 2020;16(3):919-943 Doi:10.33899/berj.2020.166004. https://www.iasj.net/iasj/article/185599.
Imran M, Aslam Gondal T, Atif M, Shahbaz M, Batool Qaisarani T, Hanif Mughal M, et al . Apigenin as an anticancer agent. Phytother Res .2020; 34(8), 1812-1828. https://doi.org/10.1002/ptr.6647.
Al-Jammas S, Al-Sarraj A. The histological changes induced by Cytarabine on rabbits livers (with and without vitamin E administration). Iraqi J Vet Sci. 2020; 34(1), 9-13. http://dx.doi.org/10.33899/ijvs.2020.163564.
Joshi M, Sodhi KS, Pandey R, Singh J, Goyal S, Prasad S, ... Mahajan S. Cancer chemotherapy and hepatotoxicity: an update. J Pharm Res Int .2014; 4(06). http://www.iajpr.com/.
Mossalam HM Fathy YA. Effect of Intraconazole on the liver of adult male albino rat and the possible protective role of coenzyme ( Histological ,immunohistochemical and biochemical study. Al Azhar Med. J. 2021; 50(1): 791-808. https://dx.doi.org/10.21608/amj.2021.139881.
El-Sayyad H , Ismail MF, Shalaby FM, Abou-El-Magd RF, Gaur RL , Fernando A ,et al . Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats . Int. J. Biol. Sci . 2009; 5(5):466-473. https://dx.doi.org/10.7150%2Fijbs.5.466.
luma khalel Hafidh A. Al-Ashoo. A histological study on the effect of imatinib on the rats' testis after early postnatal exposure. Iraqi J Vet Sci..2021; 35(1), 85-92. http://dx.doi.org/10.33899/ijvs.2020.126342.1303.
Dawood Gh A , Taqa G .A , Alnema M.M. Histological effect of COQ10 on liver and buccal mucosa in mice. J Appl Vet Sci. 2020; 5(2) : 1-5. https://dx.doi.org/10.21608/javs.2020.85543.
Mohamed DI, Khairy E, Tawfek SS, Habib EK, Fetouh MA. Coenzyme Q10 attenuates lung and liver fibrosis via modulation of autophagy in methotrexate treated rat. Biomed Pharmacother. 2019; 109: 892-901. https://doi.org/10.1016/j.biopha.2018.10.133.
Hellerbrand C. Hepatic stellate cells – The pericytes in the liver. Pflugers Arch EJ physiol.2013; 465:775-778. https://doi.org/10.1007/s00424-012-1209-5.
Gaafar AA, Salama ZA, El-Baz FK. A Comparative Study on the Active Constituents, Antioxidant Capacity and Anti-Cancer Activity of Cruciferous Vegetable Residues. Baghdad Sci.J. 2020Sep.1.17(3):0743. http://dx.doi.org/10.21123/bsj.2020.17.3.0743.