تأثیر مصرف کورکومین بر سطح تستوسترون و آنزیم‌های کبدی در رت‌های القاشده با واریکوسل

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه زیست‌شناسی، واحد شیراز، دانشگاه آزاد اسلامی، شیراز، ایران

2 پژوهشگاه رویان، پژوهشکده زیست‌فناوری جهاد دانشگاهی، مرکز تحقیقات پزشکی تولیدمثل، گروه زیست‌فناوری جانوری، اصفهان، ایران

3 گروه زیست‌شناسی، واحد مرودشت، دانشگاه آزاد اسلامی، مرودشت، ایران

چکیده

واریکوسل یکی از مهم‌ترین دلایل ناباروری در مردان است که علاوه بر تأثیر منفی بر اسپرماتوژنز، می‌تواند بر سیستم غدد درون‌ریز نیز تأثیر بگذارد. ارتباط بین واریکوسل و تولید تستوسترون مشخص نیست. کبد یکی از اندام‌های مؤثر در متابولیسم مواد و هورمون‌ها است. هدف از این مطالعه بررسی سطح تستوسترون سرم و ارتباط آن با تغییرات آنزیمی کبد بود. 50 سر رت نر نژاد ویستار به 5 گروه شامل کنترل، شم، القای واریکوسل، القای واریکوسل (50 میلی‌گرم بر کیلوگرم کورکومین) القای واریکوسل (100میلی‌گرم بر کیلوگرم کورکومین) تقسیم‌بندی شدند. پس ‌از دوره تیمار، سطح آهن (Fe2+)، تستوسترون، بیلی‌روبین نوع مستقیم (D)، بیلی‌روبین کل (T) و غلظت سرمی آلانین آمینو ترانسفراز (ALT)، آسپارتات آمینوترانسفراز (AST) ارزیابی شد و بافت کبد جداشده و موردبررسی قرار گرفت. واریکوسل موجب افزایش معنی‌دار سطح آهن (05/0 ≥ p)، کاهش غیر معنی‌دار سطح‌  تستوسترون (242/0=p) و بیلی‌روبین توتال (639/0= p) شد. درمان با کورکومین منجر به کاهش غیر معنی‌داری در سطح آهن (056/0=p ) و بیلی‌روبین توتال (639/0= p)، همچنین افزایش غیر معنی‌دار در سطح‌ تستوسترون (05/0< p) نسبت به واریکوسل شد، درحالی‌که سطح بیلی‌روبین مستقیم (05/0≥ p) در واریکوسل افزایش معنی‌داری نسبت به شم و کنترل نشان داد. استفاده از کورکومین باعث کاهش معنی‌دار آن نسبت به واریکوسل شد (03/0 = p). ارزیابی سطح ALT(762/0=p ) و AST (367/0=p ) اختلاف معنی‌داری در بین گروه‌ها نشان نداند. واریکوسل بر سطح آهن، تستوسترون، بیلی‌روبین و آنزیم‌های کبدی تأثیر منفی دارد. کورکومین علاوه بر مهار آسیب‌های ناشی از واریکوسل در بافت بیضه، قادراست تا اثرات مخرب واریکوسل را بر روی مؤلفه‌های بیوشیمیایی مرتبط با بافت کبد کاهش دهد. عصاره کورکومین در دوزهای بالاتر می‌تواند منجر به کاهش آنزیم کبدی AST دررت­های واریکوسلی گردد.

کلیدواژه‌ها


عنوان مقاله [English]

The Effect of Curcumin on Testosterone and Liver Enzyme Levels in Varicocele-induced Rats

نویسندگان [English]

  • Mohamad Reza Sadraie 1
  • Marzieh Tavalaee 2
  • Mohammad Hosein Nasr-Esfahani 2
  • Mohsen Forouzanfar 3
1 Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
2 Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
3 Department of Biology, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran
چکیده [English]

Varicocele is one of the most important causes of infertility in men, which in addition to negatively affecting spermatogenesis, can also affect the endocrine system. The link between varicocele and testosterone production is unclear. The liver is one of the most effective organs in the metabolism of substances and hormones. This study aimed to evaluate serum testosterone levels and their association with liver enzymatic changes. Fifty male Wistar rats were divided into 5 groups, including sham control, varicocele induction, varicocele induction (50 mg/kg curcumin), and varicocele induction (100 mg / kg curcumin). After the treatment period, iron (Fe2 +), testosterone, direct bilirubin, total bilirubin and serum concentrations of ALT, and AST were assessed and liver tissue was isolated and examined. Varicocele caused a significant increase in iron levels (p ≤ 0.05) and a non-significant decrease in testosterone levels (p = 0.242) and total bilirubin (T) (p = 0.639). The treatment resulted in a significant decrease in the levels of iron (p = 0.056) and total bilirubin (p = 0.639), as well as a significant increase in testosterone levels (p < 0.05) compared to the varicocele. While the level of direct bilirubin (p ≥ 0.05) in the varicocele showed a significant increase compared to the sham and control. Using curcumin significantly reduced it compared to the varicocele (p = 0.03). Evaluation of ALT (p = 0.762) and AST (p = 0.367) levels did not show a significant difference among the groups. The levels of iron, testosterone, bilirubin, and liver enzymes are negatively affected by varicocele. Curcumin may lessen the harmful effects of varicocele on biochemical components linked with liver tissue in addition to preventing varicocele damage to testicular tissue. In varicocele rats, greater dosages of curcumin may lower the liver enzyme AST.

کلیدواژه‌ها [English]

  • Curcumin
  • Testosterone
  • Seminiferous tubules
  • liver enzymes
  • Varicocele
  1. Abdel-Meguid T.A., Farsi H.M., Al-Sayyad A., Tayib A., Mosli H.A. and Halawani A.H. 2014. Effects of varicocele on serum testosterone and changes of testosterone after varicocelectomy: a prospective controlled study. Urology, 84(5): 1081-1087.
  2. Abubakar K., Mailafiya M.M., Chiroma S. M.,  Danmaigoro  A., Zyoud  T. Y.,  Abdul Rahim  E., Abu Bakar Zakaria  M.Z. 2020. Ameliorative effect of curcumin on lead‐induced hematological and hepatorenal toxicity in a rat model. Journal of Biochemical and Molecular Toxicology, 34(6): e22483.
  3. Ahmed-Farid O.A., Nasr M., Ahmed R.F. and Bakeer R.M. 2017. Beneficial effects of curcumin nano-emulsion on spermatogenesis and reproductive performance in male rats under protein deficient diet model: enhancement of sperm motility, conservancy of testicular tissue integrity, cell energy and seminal plasma amino acids content.Journal of Biomedical Science,24(1): 1-14.

 

  1. Alsaikhan B., Alrabeeah K., Delouya G. and Zini A. 2016. Epidemiology of varicocele. Asian Journal of Andrology,18(2): 179.
  2. Badria F.A., Ibrahim A.S., Badria A.F. and Elmarakby A.A. 2015. Curcumin attenuates iron accumulation and oxidative stress in the liver and spleen of chronic iron-overloaded rats.PLoS One, 10(7): e0134156.
  3. Barati E., Nikzad H., Karimian M. 2020. Oxidative stress and male infertility: Current knowledge of pathophysiology and role of antioxidant therapy in disease management.Cellular and Molecular Life Sciences,77(1): 93-113.
  4. Basciani S., Mariani S., Spera G., Gnessi L. 2010. Role of platelet-derived growth factors in the testis.Endocrine reviews,31(6): 916-939.
  5. Belay R.E., Huang G.O., Shen J.K.C., Ko E.Y.K. 2016. Diagnosis of clinical and subclinical varicocele: how has it evolved? Asian Journal of Andrology,18(2): 182.
  6. Belhadj Slimen I., Najar T., Ghram A., Dabbebi H., Ben Mrad M., Abdrabbah M. 2014. Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review.International Journal of Hyperthermia,30(7): 513-523.
  7. Bobjer J., Katrinaki M., Tsatsanis C., Giwercman Y. L., Giwercman A. 2013. Negative association between testosterone concentration and inflammatory markers in young men: a nested cross-sectional study.PLoS One, 8(4): e61466.
  8. Boroumand N., Samarghandian S., Hashemy S.I. 2018. Immunomodulatory, anti-inflammatory, and antioxidant effects of curcumin.Journal of Herbmed Pharmacology, 7(4): 211-219.
  9. Burra P. 2013. Liver abnormalities and endocrine diseases. Best Practice and Research Clinical Gastroenterology,27(4): 553-563.
  10. Bussler S., Vogel M., Pietzner D., Harms K., Buzek T., Penke M., Händel N., Körner A., Baumann U., Kiess W., Flemming G. 2018. New pediatric percentiles of liver enzyme serum levels (alanine aminotransferase, aspartate aminotransferase, γ‐glutamyltransferase): Effects of age, sex, body mass index, and pubertal stage. Hepatology, 68(4): 1319-1330.
  11. Cho C. L., Esteves S. C., Agarwal A. 2016. Novel insights into the pathophysiology of varicocele and its association with reactive oxygen species and sperm DNA fragmentation.Asian Journal of Andrology,18(2): 186-193.
  12. Davoodi M. 2012. The effect of eight weeks selected aerobic exercise on liver parenchyma and liver enzymes (AST, ALT) of fat liver patients.Journal of Shahrekord Uuniversity of Medical Sciences, 14(1):84-90. [In Persian].
  13. Farzanegi P., Habibian M., Salehi M. 2012. Interactive effect of endurance training and curcumin supplementation on some indices of liver damage in rats exposed to heavy metal lead.Daneshvar Medicine: Basic and Clinical Research Journal,20(4): 63-70.
  14. Filardi T., Varì  R.,  Ferretti  E.,  Zicari A., Morano S., Santangelo C. 2020. Curcumin: Could This Compound Be Useful in Pregnancy and Pregnancy-Related Complications? Nutrients, 12(10): 3179.
  15. Gabrielsen J.S., Lamb D.J., Lipshultz L.I. 2018. Iron and a Man’s Reproductive Health: the Good, the Bad, and the Ugly. Current urology Reports, 19(8): 1-7.
  16. Gholirad S., Razi M., Hassani Bafrani H. 2017. Tracing of zinc and iron in experimentally induced varicocele: correlation with oxidative, nitrosative and carbonyl stress. Andrologia,49(6): e12687.
  17. Giordano A., Tommonaro G. 2019. Curcumin and cancer.Nutrients,11(10): 2376.
  18. Hamoud A.R., Weaver L., Stec D.E., Hinds Jr T. D. 2018. Bilirubin in the liver–gut signaling axis.Trends in Endocrinology and Metabolism,29(3): 140-150.
  19. Hamzavi Jahromi Z., Zolghadri Jahromi S., Hemayatkhah Jahromi V. 2014. Protective Effect of Curcumin on Hormones of Spermatogenesis and DNA Breaks in Rats Exposed to Gamma-radiation. Journal of Animal Biology, 6(3): 25-36. [In Persian]
  20. Hasanzadeh S., Sadrkahnlou R.A., Farshid M. 2011. An investigation of ultrastructural changes in cells of seminiferous tubules of testes and alterations in gonadotropic-gonadal hormones of adult male experimentally induced diabetic rats.Studies in Medical Sciences,22(3): 239-248.
  21. Hassanin A.M., Ahmed H.H., Kaddah A.N. 2018. A global view of the pathophysiology of varicocele.Andrology,6(5): 654-661.
  22. Hayden R.P., Tanrikut C. 2016. Testosterone and varicocele.Urologic Clinics,43(2): 223-232.
  23. Izadpanah M., Alizadeh R., Minaee M. B., Heydari L., Babatunde A., Abbasi M. 2015. The effects of curcumin on sperm parameters and nitric oxide production in varicocelized rats Efectos de la cúrcuma sobre los pará metros espermá ticos y producción de óxido nÃtrico en ratas varicocelizadas.International Journal of Morphology,33(4): 1530-1535.
  24. Kelardeh B.M., Azarbayjani M.A., Peeri M., Homaee H.M. 2016. Effect of curcumin supplementation and resistance training in patients with nonalcoholic fatty liver disease.Journal of Medicinal Plants,15(60): 1-9.
  25. Khosravanian H., Razi M., Farokhi F., Khosravanian N. 2015. Simultaneous administration of dexamethasone and vitamin E reversed experimental varicocele-induced impact in testicular tissue in rats; correlation with Hsp70-2 chaperone expression International Brazilian Journal of Urology,41(4): 773-790.
  26. Kiziler A.R., Aydemir B., Guzel S., Yazici C. M., Gulyasar T., Malkoc E., Acar A. 2015. Comparison of before and after varicocelectomy levels of trace elements, nitric oxide, asymmetric dimethylarginine and malondialdehyde in the seminal plasma and peripheral and spermatic veins.Biological trace element research,167(2): 172-178.
  27. Ko E. Y., Sabanegh Jr E. S., Agarwal A. 2014. Male infertility testing: reactive oxygen species and antioxidant capacity.Fertility and sterility,102(6): 1518-1527.
  28. Ko K.W., Chae J.Y., Kim S.W., Moon D.G., Kim J.J., Yoon D.K., Park J.Y. 2010. The effect of the partial obstruction site of the renal vein on testis and kidney in rats: is the traditional animal model suitable for varicocele research? Korean Journal of Urology,51(8): 565.
  29. Lomboy J.R., Coward R.M. 2016. Men's Health: The Varicocele: Clinical Presentation, Evaluation, and Surgical Management. InSeminars in interventional radiology. Thieme Medical Publishers, 33(3): 163.
  30. Mahmoud A.A., Abdelrahman A., Abd el Aziz H.O. 2018. Protective effect of curcumin on the liver of high fat diet-fed rats.Gene Reports,11: 18-22.
  31. Malespin M., Nassri A. 2019. Endocrine diseases and the liver: an update.Clinics in liver disease,23(2): 233-246.
  32. Mailafiya M.M., Abubakar K., Chiroma S. M., Danmaigoro A., Rahim E. B. A., Moklas M. A. M., Zakaria Z. A. B. 2020. Curcumin-loaded cockle shell-derived calcium carbonate nanoparticles: A novel strategy for the treatment of lead-induced hepato-renal toxicity in rats. Saudi Journal of Biological Sciences, 27(6): 1538-1552.
  33. Missassi G., dos Santos Borges C., de Lima Rosa J., Villela e Silva P., da Cunha Martins A., Barbosa F., De Grava Kempinas W. 2017. Chrysin administration protects against oxidative damage in varicocele-induced adult rats.Oxidative Medicine and Cellular Longevity, 2017:1-12.
  34. Mohebbati, R., Anaeigoudari, A., Khazdair, M.R. 2017. The effects of Curcuma longa and curcumin on reproductive systems.Endocrine regulations,51(4): 220-228.
  35. Molina A.M., Moyano M.R., Serrano-Rodriguez J.M., Ayala N., Lora A.J., Serrano-Caballero J.M. 2015. Analyses of anaesthesia with ketamine combined with different sedatives in rats.Veterinarni Medicina,60(7):368-375.
  36. Ni F.D., Hao S.L., Yang W.X. 2019. Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis.Cell Death and Disease,10(8): 1-15.
  37. Panahi Y., Kianpour P., Mohtashami R., Jafari R., Simental-Mendía L.E., Sahebkar A. 2017. Efficacy and safety of phytosomal curcumin in non-alcoholic fatty liver disease: a randomized controlled trial.Drug research, 67(4): 244-251.
  38. Pastuszak A. W., Wang R. 2015. Varicocele and testicular function.Asian Journal of Andrology,17(4): 659.
  39. Pei K., Gui T., Kan D., Feng H., Jin Y., Yang Y., Zhang Q., Du Z., Gai Z., Wu J., Li Y. 2020. An overview of lipid metabolism and nonalcoholic fatty liver disease. BioMed Research, International, 2020:1-12.
  40. Rainey N. E., Moustapha A., Saric A., Nicolas G., Sureau F., Petit P. X. 2019. Iron chelation by curcumin suppresses both curcumin-induced autophagy and cell death together with iron overload neoplastic transformation.Cell death discovery, 5(1): 1-15.
  41. Razi M., Sadrkhanloo R.A., Malekinejad H., Sarafzadeh-Rezaei F. 2011. Varicocele time-dependently affects DNA integrity of sperm cells: evidence for lower in vitro fertilization rate in varicocele-positive rats.International Journal of Fertility and sterility,5(30): 174.
  42. Rezvanirad A., Mardani M., Ahmadzadeh S. M., Asgary S., Naimi A., Mahmoudi G. 2016. Curcuma longa: A review of therapeutic effects in traditional and modern medical references.Journal of Chemical and Pharmaceutical Sciences,9(4): 3438-3448.
  43. Sadoughi S.D., Edalatmanesh M.A., Rahbarian R., 2018. The Effect of Curcumin on Pituitary-Gonadal Axis, DNA Oxidative Damage and Antioxidant Enzymes Activity of Testicular Tissue in Male Diabetic Rats.Journal of Fasa University of Medical Sciences,7(4): 511-520.
  44. Salem N.A., Alnahdi H.S., Ibrahim G.S., 2017. Therapeutic effect of curcumin against nicotine-induced reproductive dysfunction in male rats.Journal of Innovations in Pharmaceuticals and Biological Sciences,4(4): 26-31.
  45. Salmani S., Razi M., Sarrafzadeh-Rezaei F., Mahmoudian A., 2020. Testosterone amplifies HSP70-2a, HSP90 and PCNA expression in experimental varicocele condition: Implication for DNA fragmentation.Reproductive Biology,20(3): 384-395.
  46. Simsek A., Ozbek E., Ilbey Y.O., Cekmen M.U.S. T., Somay A., Tasci A. I., 2012. Potential role of p38‐mitogene‐activated protein kinase and nuclear factor‐kappa B expression in testicular dysfunction associated with varicocele: an experimental study.Andrologia,44: 94-101.
  47. Soochan D., Keough V., Wanless I. Molinari M. 2012. Intra and extra-hepatic cystadenoma of the biliary duct. Review of literature and radiological and pathological characteristics of a very rare case. BMJ Case Reports, 2012: bcr0120125497.
  48. Sudjarwo S.A., Giftania Wardani Sudjarwo, K. 2017. Protective effect of curcumin on lead acetate-induced testicular toxicity in Wistar rats.Research in pharmaceutical sciences,12(5): 381.
  49. Szabó M., Veres Z., Bátai-Konczos A., Kékesi O., Kis E., Szabó, K., Jemnitz K., 2014. Statins alter the hepatobiliary transport of unconjugated and conjugated bilirubin in sandwich-cultured rat hepatocytes. Toxicology in vitro, 28(6): 1136-1143.
  50. Tanrikut C., Goldstein M., Rosoff  J. S., Lee R. K., Nelson C. J., Mulhall J.P. 2011. Varicocele as a risk factor for androgen deficiency and effect of repair. BJU International, 108(9): 1480-1484.
  51. Wagner K.H., Wallner M., Mölzer C., Gazzin S., Bulmer A.C., Tiribelli C., Vitek L. 2015. Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases.Clinical science,129(1): 1-25.
  52. Wang Y., Yu C., Pan Y., Yang X., Huang Y., Feng Z., Li X., Yang S., Liang G. 2012. A novel synthetic mono-carbonyl analogue of curcumin, A13, exhibits anti-inflammatory effects in vivo by inhibition of inflammatory ediators.Inflammation,35(2): 594-604.
  53. Watt M. J., Miotto P. M., De Nardo W., & Montgomery M. K. 2019. The liver as an endocrine organ linking NAFLD and insulin resistance.Endocrine reviews,40(5): 1367-1393.
  54. Yamaçake K.G.R., Cocuzza M., Torricelli F.C.M., Tiseo B.C., Frati R., Freire G.C., Antunes A.A., Srougi M. 2016. Impact of body mass index, age and varicocele on reproductive hormone profile from elderly men.International Brazilian Journal of Urology, 42(2): 365-372.