Pathophysiological study of atorvastatin drug on toxicity induced by D-galactose in liver of experimental rats
Keywords:
Atorvastatin Drug, Toxicity in Liver, D-galactoseAbstract
Background: This study was designed to clarify the toxic effect of a high dose of atorvastatin and the palliative effect of low doses of atorvastatin on toxicity induced by D-galactose in the liver, kidney, and adrenal gland organs. The current study was conducted on 36 healthy adult male Wistar albino rats (Rattus norvegicus) who were sexually mature at the age of 8-10 weeks and weighed between 200 and 250 grams in the animal house of Pharmacy College/ Basrah University. Methods: These rats were selected and divided into six main groups of equal weight, each with six rats. The first group (control) was drenched in (1) mL of normal saline. The second group was drenched in a single dose of atorvastatin (150 mg per kg B.W), the third received D-galactose at a dose of (500 mg per kg B.W), and the fourth group was treated with both D-galactose and atorvastatin (10 mg per kg B.W), the fifth group was coadministered with both D-galactose and atorvastatin (20 mg per kg B.W), and the sixth group where rats cotreated with Dgalactose and atorvastatin (40 mg per kg B.W). The treatment was extended for 8 weeks.
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Abed Al-kareem Z., Kadhim S., H Naser I. H., (2020), A Comparative Study between Atorvastatin and Pitavastatin Toxicity on Liver and Kidney in Albino Rats. Systematic Reviews in Pharmacy; 11(10): 1224-1227. https://doi:10.31838/srp.2020.10.175
Astegiano, M., Sapone, N., Demarchi, B., Rossetti, S., Bonardi, R., Rizzetto, M., (2004). Laboratory evaluation of the patient with liver disease. Eur. Rev. Med. Pharmacol. Sci. 8, 3–9.
Badibostan, H., Mehri, S., Mohammadi, E., & Hosseinzadeh, H. (2019). Protective effect of thymoquinone on D-galactose-induced aging in mice. Jundishapur Journal of Natural Pharmaceutical Products, 14(1), 14–23. https://doi.org/10.5812/jjnpp.13911
Bhardwaj, S. S., & Chalasani, N. (2007). Lipid-Lowering Agents That Cause Drug-Induced Hepatotoxicity. Clinics in Liver Disease, 11(3), 597–613. https://doi:10.1016/j.cld.2007.06.010
Boland, B. S., Dong, M. H., Bettencourt, R., Barrett-Connor, E., & Loomba, R. (2014). Association of Serum Bilirubin with Aging and Mortality. Journal of Clinical and Experimental Hepatology, 4(1), 1–7. https://doi:10.1016/j.jceh.2014.01.003
Chen H-l, Wang C-H, Kuo Y-W, Tsai C-H (2011) Antioxidative and hepatoprotective effects of fructo-oligosaccharide in D-galactose-treated Balb/cJ mice. Brit J Nutr 105:805–809. https://doi.org/10.1017/ s000711451000437x.
Chen, P., Chen, F., & Zhou, B. (2018). Antioxidative, anti-inflammatory and antiapoptotic effects of ellagic acid in liver and brain of rats treated by D-galactose. Scientific Reports, 8(1). https://doi:10.1038/s41598-018197320
Çoban, J., Betül-Kalaz, E., Küçükgergin, C., Aydın, A. F., Doğan-Ekici, I., DoğruAbbasoğlu, S., & Uysal, M. (2014). Blueberry treatment attenuates D-galactoseinduced oxidative stress and tissue damage in rat liver. Geriatrics & Gerontology International, 14(2), 490–497. https://doi:10.1111/ggi.12096
Cray, C., Rodriguez, M., Zaias, J., & Altaian, N. H. (2009). Effects of storage temperature and time on clinical biochemical parameters from rat serum. Journal of the American Association for Laboratory Animal Science, 48(2), 202–204.
Daniele Pastori; Arianna Pani; Arianna Di Rocco; Danilo Menichelli; Gianluca Gazzaniga; Alessio Farcomeni; Laura D'Erasmo; Francesco Angelico; Maria Del Ben; Francesco Baratta; (2021). Statin liver safety in non‐alcoholic fatty liver disease: A systematic review and metanalysis. British Journal of Clinical Pharmacology. https://doi.org/10.1111/bcp.14943
Einar Björnsson; Elin I. Jacobsen; Evangelos Kalaitzakis (2012). Hepatotoxicity associated with statins: Reports of idiosyncratic liver injury post-marketing. , 56(2), 0–380. https://doi:10.1016/j.jhep.2011.07.023
El-Baz, F. K., Hussein, R. A., Abdel Jaleel, G. A. R., & Saleh, D. O. (2018). Astaxanthin-Rich Haematococcus pluvialis Algal Hepatic Modulation in DGalactose-Induced Aging in Rats: Role of Nrf2. Advanced Pharmaceutical Bulletin, 8(3), 523–528. https://doi:10.15171/apb.2018.061
Feng Y et al (2016) Chlorogenic acid protects D-galactose-induced liver and kidney injury via antioxidation and antiinflammation effects in mice. Pharm Biol 54:1–8. https://doi.org/10.3109/13880209.2015.1093510
Gao, J., Yu, Z., Jing, S., Jiang, W., Liu, C., Yu, C., … Li, H. (2018). Protective effect of Anwulignan against D-galactose-induced hepatic injury through activating p38 MAPK–Nrf2–HO-1 pathway in mice. Clinical Interventions in Aging, Volume 13, 1859–1869. https://doi:10.2147/cia.s173838
Gomes, A. S., Gadelha, G. G., Lima, S. J., Garcia, J. A., Medeiros, J. V. R., Havt, A., … Souza, M. H. L. P. (2010). Gastroprotective effect of heme-oxygenase 1/biliverdin/CO pathway in ethanol-induced gastric damage in mice. European Journal of Pharmacology, 642(1-3), 140–145. https://doi:10.1016/j.ejphar.2010.05.023
Hu, Z., Lausted, C., Yoo, H., Yan, X., Brightman, A., Chen, J., Wang, W., Bu, X., & Hood, L. (2014). Quantitative liver-specific protein fingerprint in blood: A signature for hepatotoxicity. In Theranostics (Vol. 4, Issue 2, pp. 215–228). https://doi.org/10.7150/thno.7868
Huang CC, Chiang WD, Huang WC, Huang CY, Hsu MC, Lin WT (2013). Hepatoprotective effects of swimming exercise against D-galactose-induced senescence rat model. Evid Based Complement Altern Med. https://doi.org/10.1155/ 2013/27543
Huisa, B. N., Stemer, A. B., & Zivin, J. A. (2010). Atorvastatin in stroke: A review of SPARCL and subgroup analysis. Vascular Health and Risk Management, 6(1), 229–236. https://doi.org/10.2147/vhrm.s6795
Jabir, S. H., & Jaffat, H. S. (2018). Effects of atorvastatin drug in albino male rats. Journal of Pharmaceutical Sciences and Research, 10(11), 2924–2928.
Ji M et al (2017).Comparison of naturally aging and D-galactose induced aging model in beagle dogs. Exp Ther Med 14:5881–5888
Jiang, H., & Zheng, H. (2019). Efficacy and adverse reaction to different doses of atorvastatin in the treatment of type II diabetes mellitus. Bioscience Reports, 39(7), 1–10. https://doi.org/10.1042/BSR20182371
Karahalil, Bensu; Hare, Emine; Koç, Göksel; Uslu, İrem; Şentürk, Kerem; Özkan, Yağmur (2017) .Hepatotoxicity associated with statins. Archives of Industrial Hygiene and Toxicology, 68(4). https://doi:10.1515/aiht-2017-68-2994
Kawata, S., Yamasaki, E., Nagase, T., Inui, Y., Ito, N., Matsuda, Y., … Matsuzawa, Y. (2001) .Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial. British Journal of Cancer, 84(7), 886–891. https://doi:10.1054/bjoc.2000.1716
Khidoyatova, M. R., Kayumov, U. K., Inoyatova, F. K., Fozilov, K. G., Khamidullaeva, G. A., & Eshpulatov, A. S. (2022). Clinical status of patients with coronary artery disease post COVID-19. International Journal of Health & Medical Sciences, 5(1), 137-144. https://doi.org/10.21744/ijhms.v5n1.1858
Kong, S.-Z., Li, J.-C., Li, S.-D., Liao, M.-N., Li, C.-P., Zheng, P.-J., … Hu, Z. (2018). Anti-Aging Effect of Chitosan Oligosaccharide on D-galactose-Induced Subacute Aging in Mice. Marine Drugs, 16(6), 181. https://doi:10.3390/md16060181
Lei L, Ou L, Yu X (2016).The antioxidant effect of Asparagus cochinchinensis (Lour.) Merr. shoot in D-galactose induced mice aging model and in vitro. J Chin Med Assoc 79:205–211
Li L et al (2005) Antioxidant activity of gallic acid from rose flowers in senescence accelerated mice. Life Sci 77:230–240. https://doi.org/10.1016/j.lfs.2004.12.024
Lin X, Xia Y, Wang G, Xiong Z-Q, Zhang H, Lai F, Ai L (2018) Lactobacillus plantarum AR501 alleviates the oxidative stress of D-galactose-induced aging mice liver by upregulation of Nrf2-mediated antioxidant enzyme expression. J Food Sci.
Liu H, Pei X, Wang J, Zhou Y, Wang L, Qi B (2018). Effect of loach paste on the liver and immune organs of D-galactoseinduced ageing mice. Food Agric Immunol 29:316–3
Liu J, Chen D, Wang Z, Chen C, Ning D, Zhao S (2019). Protective effect of walnut on D-galactose-induced aging mouse model. Food Sci Nutr 7:969–976
Luna, L. G., (1968). Manual of histologic staining methods of the Armed Forces Institute of Pathology. 3rd Edition, Mc Graw-Hill, New York.
Mo ZZ et al (2017). Protective effect of SFE-CO2 of ligusticum chuanxiong hort against D-galactose-induced injury in the mouse liver and kidney. Rejuv Res 20:231–243
Mohammadi E, Mehri S, Bostan HB, Hosseinzadeh H (2018). Protective effect of crocin against D-galactose-induced aging in mice. Avicenna J Phytomed 8:14 Muchova, L., Wong, R. J., Hsu, M., Morioka, I., Vitek, L., Zelenka, J., … Stevenson, D. K. (2007). Statin treatment increases formation of carbon monoxide and bilirubin in mice: a novel mechanism of in vivo antioxidant protection. Canadian Journal of Physiology and Pharmacology, 85(8), 800–810. https://doi:10.1139/y07-077
Mustafa T. A., Abdulah H. O., (2019). Histological Alterations Induced by Atorvastatin Therapeutic Doses in some Organs of Male Albino Rats. Polytechnic Journal. Vol. 9, No 1: PP13-16. Erbil Polytechnic University, Erbil, Kurdistan Region - F.R. Iraq. https://doi:10.25156/ptj.v9n1y2019.pp13-16
Nam, Y., Bae, J., Jeong, J. H., Ko, S. K., & Sohn, U. D. (2017). Protective effect of ultrasonication-processed ginseng berry extract on the D-galactosamine/lipopolysaccharide-induced liver injury model in rats. Journal of Ginseng Research. https://doi:10.1016/j.jgr.2017.07.007
Noureen S, Riaz A, Arshad M, Arshad N (2019) In vitro selection and in vivo confirmation of the antioxidant ability of Lactobacillus brevis MG 000874. J Appl Microbiol 126:1221–1232
Panonnummal R., Varkey J., (2014). Statins induced nephrotoxicity: a dose dependent study in albino rats. Int J Pharm Pharm Sci 6 (11), 401.406-
Reddy, A. Gopala; Rao, G. Srinivasa; Haritha, C.; Jyothi, K.; Reddy, G. Dilip, (2010). Interaction study on garlic and atorvastatin with reference to nephrotoxicity in dyslipidaemic rats. Toxicology International, 17(2), 90–93. https://doi:10.4103/0971-6580.72678
Roller, J., Laschke, M. W., Scheuer, C., & Menger, M. D. (2010). Heme oxygenase (HO)-1 protects from lipopolysaccharide (LPS)-mediated liver injury by inhibition of hepatic leukocyte accumulation and improvement of microvascular perfusion. Langenbeck’s Archives of Surgery, 395(4), 387–394. https://doi:10.1007/s00423-010-0603-8
Sahebkar, A., Rathouska, J., Simental-Mendía, L. E., & Nachtigal, P. (2016). Statin therapy and plasma cortisol concentrations: A systematic review and metaanalysis of randomized placebo-controlled trials. Pharmacological Research, 103, 17–25. https://doi.org/10.1016/j.phrs.2015.10.013
Saleh, D. O., Mansour, D. F., Hashad, I. M., & Bakeer, R. M. (2019). Effects of sulforaphane on D-galactose-induced liver aging in rats: Role of keap-1/nrf-2 pathway. European Journal of Pharmacology. https://doi:10.1016/j.ejphar.2019.04.043
Salman A. H. (2021). Evaluation the role of vitamin D3 on some physiological and histopathological in liver fibrosis induced in male rats. MSc. thesis. biological dep. Sciences College Basrah University.
Shahroudi MJ, Mehri S, Hosseinzadeh H. (2017). Anti-aging effect of Nigella sativa fixed oil on D-galactose-induced aging in mice. J Pharmacopunct 20:29
Suryasa, I. W., Rodríguez-Gámez, M., & Koldoris, T. (2021). Get vaccinated when it is your turn and follow the local guidelines. International Journal of Health Sciences, 5(3), x-xv. https://doi.org/10.53730/ijhs.v5n3.2938
Taghipour, Z., Kaviani, E., Kaeidi, A., Shamsizadeh, A., Hassanshahi, J., & Fatemi, I. (2019). Atorvastatin attenuates D-galactose-induced hepatorenal toxicity in mice: An experimental study with histopathological evaluations. Physiology and Pharmacology (Iran), 23(1), 36–43.
Wang H et al. (2018) Inorganic nitrate alleviates the senescence-related decline in liver function. Sci China Life Sci. https://doi.org/10.1007/s11427-017-9207-x
Ward, N. C., Watts, G. F., & Eckel, R. H. (2019). Statin Toxicity: Mechanistic Insights and Clinical Implications. Circulation Research, 124(2), 328–350. https://doi.org/10.1161/CIRCRESAHA.118.312782
Xu LQ et al (2016). Polydatin attenuates D-galactose-induced liver and brain damage through its anti-oxidative, anti-inflammatory and anti-apoptotic effects in mice. Food Funct. https://doi.org/10.1039/c6fo01057a
Yang J, He Y, Zou J, Xu L, Fan F, Ge Z (2019). Effect of Polygonum Multiflorum Thunb on liver fatty acid content in aging mice induced by D-galactose. Lipids Health Dis 18:128.
Zhuang Y, Ma Q, Guo Y, Sun L (2017) Protective effects of rambutan (Nephelium lappaceum) peel phenolics on H2O2-induced oxidative damages in HepG2 cells and Dgalactose-induced aging mice. Food Chem Toxicol 108:554– 562.
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