Protective Effect of Genistein on the Morphine-Induced Kidney Disorders in Male Mice
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Medical Biology Research Center, Department of Anatomical Sciences, Kermanshah University of Medical Sciences, Kermanshah, IRAN
Department of Anatomical Sciences, Medical School, Kermanshah University of Medical Sciences, Kermanshah, IRAN
Students research committee, Department of Anatomical Sciences, Kermanshah university of Medical Sciences Kermanshah, IRAN
Online publication date: 2020-03-21
Publication date: 2020-03-21
Electron J Gen Med 2020;17(3):em213
Morphine is a member of the naturally occurring phenanthrene alkaloids of opium. Genistein is a phytoestrogen, present in soy products. This study was designed to evaluate protective effects of genistein against morphine induced damages to the kidneys of mice.

In this study, 48 male mice were randomly assigned to 8 groups: control (saline), morphine treated group (10 mg/kg/day); genistein groups (1, 2, 4 mg/kg/day) and morphine plus genistein treated group. Drugs were administrated intraperitoneally for 30 consequent days. Weight of animals and kidneys, glomeruli characteristics, kidney function markers and blood serum nitric oxide level has been studied.

The results indicated that morphine administration significantly increased Lactate dehydrogenase (LDH), Blood urea nitrogen (BUN), creatinine and nitric oxide levels compared to the control ( saline) group (P<0.05). Genistein in all doses and genistein plus morphine at the dose of 4 mg/kg significantly decreased LDH, BUN, creatinine, glomerular diameter and nitric oxide levels compared to the control and morphine groups (p<0.05).

It seems that genistein administration improved kidney damages induced by morphine in mice.

Seth P, Scholl L, Rudd RA, Bacon S. Overdose deaths involving opioids, cocaine, and psychostimulants—United States, 2015–2016. Am J Transplant. 2018;18(6):1556-68. https://doi.org/10.1111/ajt.14....
Jalili C, Ahmadi S, Roshankhah S, Salahshoor M. Effect of Genistein on reproductive parameter and serum nitric oxide levels in morphine-treated mice. Int J Reprod Biomed. 2016;14:95. https://doi.org/10.29252/ijrm.....
Pert CB, Snyder SH. Opiate receptor: demonstration in nervous tissue. Science. 1973;179(4077):1011-4. https://doi.org/10.1126/scienc... PMid:4687585.
Salahshoor MR. Protective effect of crocin on liver toxicity induced by morphine. Res Pharm Sci. 2016;11:120.
Desmedt S, Spinewine A, Jadoul M, Henrard S, Wouters D, Dalleur O. Impact of a clinical decision support system for drug dosage in patients with renal failure. Int J Clin Pharm. 2018;21:1-9. https://doi.org/10.1007/s11096... PMid:29785684.
Ahmadnia H, Ghanbari M, Moradi MR, Khaje-Dalouee M. Effect of cigarette smoke on spermatogenesis in rats. J Urol. 2009;4(3):159-63.
Mercadante S, Arcuri E. Opioids and renal function. The Journal of Pain 2004;5(1):2-19. https://doi.org/10.1016/j.jpai... PMid:14975374.
Jalili C, Tabatabaei H, Kakaberiei S, Roshankhah S, Salahshoor MR. Protective role of Crocin against nicotine induced damages on male mice liver. Int J Prev Med. 2015;6:92. https://doi.org/10.4103/2008-7... PMid:26442615 PMCid:PMC4593238.
Gibanananda RS. Oxidants, antioxidants and carcinogenesis. Indian J Exp Biol 2002;40:1213-32.
Zarrindast M, Delphi L. Morphine-induced Nitric Oxide Production in PC12 Cells. Arch Iran Med. 2012;15:404-8.
Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL. Maternal genistein alters coat color and protects A vy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect. 2006:567-72. https://doi.org/10.1289/ehp.87... PMid:16581547 PMCid:PMC1440782.
Salahshoor MR, Roshankhah S, Hosseni P, Jalili C. Genistein Improves Liver Damage in Male Mice Exposed to Morphine. Chin Med J 2018;131:1598-604. https://doi.org/10.4103/0366-6... PMid:29941714 PMCid:PMC6032674.
Choi M, Jung U, Yeo J, Kim M, Lee M. Genistein and daidzein prevent diabetes onset by elevating insulin level and altering hepatic gluconeogenic and lipogenic enzyme activities in non‐obese diabetic (NOD) mice. Diabetes Metab Res Rev. 2008;24(1):74-81. https://doi.org/10.1002/dmrr.7... PMid:17932873.
Rajaram S. The effect of vegetarian diet, plant foods, and phytochemicals on hemostasis and thrombosis. Am J Clin Nutr. 2003;78(3):552S-8S. https://doi.org/10.1093/ajcn/7... PMid:12936949.
Dattner AM. From medical herbalism to phytotherapy in dermatology: back to the future. Dermatologic therapy. 2003;16(2):106-13. https://doi.org/10.1046/j.1529... PMid:12919112.
Jalili C, Salahshoor MR, Hoseini M, Roshankhah S, Sohrabi M, Shabanizadeh A. Protective Effect of Thymoquinone Against Morphine Injuries to Kidneys of Mice. Iran J Kidney Dis. 2017;11(2).142-150.
Salahshoor M, Mohamadian S, Kakabaraei S, Roshankhah S, Jalili C. Curcumin improves liver damage in male mice exposed to nicotine. J Tradit Complement Med. 2016;6:176-83. https://doi.org/10.1016/j.jtcm... PMid:27114942 PMCid:PMC4833467.
Roshankhah Sh, Salahshoor MR, Jalili F, Karimi F, Sohrabi M, Jalili C. Crocin effects on the nicotine-induce ovary injuries in female rat. Int J Life Sci. Pharma 2017;7:1-8.
Lei L, Liu S, Li Y, Song H, He L, Liu Q, et al. The potential role of glucokinase activator SHP289-04 in anti-diabetes and hepatic protection. European journal of pharmacology. 2018 May 5;826:17-23. https://doi.org/10.1016/j.ejph... PMid:29477658.
Muangman V, Cherdshewasart W. Clinical trial of the phytoestrogen-rich herb, Pueraria mirifica as a crude drug in the treatment of symptoms in menopausal women. Siriraj Medical Journal. 2018;53(5):300-9.
Yoshida S, Tajiri T, Yahara T, Yoshizumi T, Tanaka K, Muraoka T, et al. Administration of opiate receptor antagonist inhibits mucosal atrophy of the gut in fasting rats. J Surg Res. 2000;93(1):177-81. https://doi.org/10.1006/jsre.2... PMid:10945961.
Heim M, Frank O, Kampmann G, Sochocky N, Pennimpede T, Fuchs P, et al. The phytoestrogen genistein enhances osteogenesis and represses adipogenic differentiation of human primary bone marrow stromal cells. Endocrinology. 2004;145(2):848-59. https://doi.org/10.1210/en.200... PMid:14605006.
King TJ, Shandala T, Lee AM, Foster BK, Chen K-M, Howe PR, et al. Potential effects of phytoestrogen genistein in modulating acute methotrexate chemotherapy-induced osteoclastogenesis and bone damage in rats. Int J Mol Sci. 2015;16(8):18293-311. https://doi.org/10.3390/ijms16... PMid:26258775 PMCid:PMC4581246.
Santell RC, Chang YC, Nair MG, Helferich WG. Dietary genistein exerts estrogenic effects upon the uterus, mammary gland and the hypothalamic/pituitary axis in rats. Int J Nutr. 1997 Feb 1;127(2):263-9. https://doi.org/10.1093/jn/127... PMid:9039826.
Rezazadeh H, Kahnouei MH, Hassanshahi G, Allahtavakoli M, Shamsizadeh A, Roohbakhsh A, et al. Regulatory effects of chronic low-dose morphine on nitric oxide level along with baroreflex sensitivity in two-kidney one-clip hypertensive rats. Iran J Kidney Dis. 2014;8(3):194.
Liu D, Homan LL, Dillon JS. Genistein acutely stimulates nitric oxide synthesis in vascular endothelial cells by a cyclic adenosine 5’-monophosphate-dependent mechanism. Endocrinology. 2004;145(12):5532-9. https://doi.org/10.1210/en.200... PMid:15319357.
Leffel EK, Wolf C, Poklis A, White KL. Drinking water exposure to cadmium, an environmental contaminant, results in the exacerbation of autoimmune disease in the murine model. Toxicology. 2003;188(2):233-50. https://doi.org/10.1016/S0300-....
Atici S, Cinel I, Cinel L, Doruk N, Eskandari G, Oral U. Liver and kidney toxicity in chronic use of opioids: an experimental long term treatment model. Journal of biosciences. 2005;30(2):245-252. https://doi.org/10.1007/BF0270... PMid:15886461.
Javanbakht MH, Sadria R, Djalali M, Derakhshanian H, Hosseinzadeh P, Zarei M, et al. Soy protein and genistein improves renal antioxidant status in experimental nephrotic syndrome. Nefrologia. 2014;34(4):483-90.
Santell RC, Chang YC, Nair MG, Helferich WG. Dietary genistein exerts estrogenic effects upon the uterus, mammary gland and the hypothalamic/pituitary axis in rats. The Journal of nutrition. 1997;127(2):263-9. https://doi.org/10.1093/jn/127... PMid:9039826.
Sung MJ, Kim DH, Jung YJ, Kang KP, Lee AS, Lee S, et al. Genistein protects the kidney from cisplatin-induced injury. Kidney international. 2008;74(12):1538-47. https://doi.org/10.1038/ki.200... PMid:18716605.
Loei MA, Mami S, Parviz SA. The effect of the opium addiction on histological structure of liver and kidney in rabbits. 2013:32-45.
Lyman J. Blood urea nitrogen and creatinine. Emergency medicine clinics of North America. 1986;4(2):223-33.
Hall AM, Unwin RJ. The not so ‘mighty chondrion’: emergence of renal diseases due to mitochondrial dysfunction. Nephron Physiology. 2006;105(1):p1-p10. https://doi.org/10.1159/000096... PMid:17095876.
Zaragoza A, Andrés D, Sarrión D, Cascales Ma. Potentiation of thioacetamide hepatotoxicity by phenobarbital pretreatment in rats. Inducibility of FAD monooxygenase system and age effect. Chemico-Biological Interactions. 2000;124(2):87-101. https://doi.org/10.1016/S0009-....
Khodadadi S, Naghsh N, Mashayekh A. Effects of Silver Nanoparticle on Phosphocreatine kinase and Histological Changes of Skeletal Muscle Tissue in Male Wistar Rat. J Mazand Univ Med Sci. 2013;23(97):36-41.
Samarghandian S, Afshari R, Farkhondeh T. Effect of long-term treatment of morphine on enzymes, oxidative stress indices and antioxidant status in male rat liver. Int J Clin Exp Med. 2014;7(5):1449-53.
Shahsavar F, Ghanadi K, Jafarzadeh M, Nasiri B, Forutani SH. Opium addiction decreases T3 uptake amount. Life Science Journal. 2013; 10(5s):608-10.