Effect of Crocin on Pituitary-Testicle Hormonal Axis in Alloxan-Induced Diabetic Male Rats

Document Type : Original Article

Author

Department of Biology, Faculty of Sciences, Payame-Noor University, Tehran, Iran.

10.32592/JSMJ.22.3.390

Abstract

Background and Objectives Diabetes mellitus is a metabolic disease which causes disorders in the reproductive system. Recent studies have revealed that the main components of saffron like crocin and safranal have several physiological effects on different biological systems. Given the role of crocin in the modulation of antioxidant defense system, this study aimed to determine the effect of crocin on pituitary-testicle hormonal axis in alloxan-induced diabetic male rats. Subjects and Methods In this experimental study, 28 Wistar male rats were allocated into 4 equal groups: control, diabetic control, and two diabetic groups treated with crocin at two concentrations. Induction of diabetes in the diabetic control and the diabetic groups treated with crocin was done by an intraperitoneal injection of 240 mg/kg alloxan. Crocin at concentrations of 50 and 100 mg/kg [0.5 ml] was intraperitoneally injected into the two diabetic groups for 25 days. Saline solution [0.5 ml] was injected into the animals in the control and diabetic control groups for 25 days. At the end of the treatment period, serum levels of LH, FSH, estrogen, testosterone and DHT were measured by ELISA. Statistical analysis was carried out using one-way ANOVA and Tukey post hoc test. P <0.05 was considered statistically significant. Results Compared with the diabetic control group, administration of crocin at concentrations of 50 and 100 mg/kg significantly increased serum levels of LH, FSH, estrogen, and DHT testosterone in a dose-dependent manner [p<0.05]. Conclusion The results show that by increasing the activity of pituitary-testicle hormonal axis, crocin improves hormonal disorders in diabetic rats.

Highlights

 [Google Scholar ][Pum Med]Raheleh Rahbarian     

Keywords

Main Subjects


[1] Alzaman N, Ali A. Obesity and diabetes mellitus in the Arab world. Journal of Taibah University Medical Sciences. 2016 Aug 1;11(4):301-9. [10.1016/j.jtumed.2016.03.009] [Link]
[2] Seyfaddini R. Ti: Cognitive function in diabetes mellitus patients. American Journal of Apllied Sciences. 2006 Jan 1;3(1):1682-4. [Link]
[3] Santilli F, Lapenna D, La Barba S, Davi G. Oxidative stress-related mechanisms affecting response to aspirin in diabetes mellitus. Free Radical Biology and Medicine. 2015 Mar 1;80:101-10. [10.1016/j.freeradbiomed.2014.12.010 ] [PMID]
[4] Cohen G, Riahi Y, Sunda V, Deplano S, Chatgilialoglu C, Ferreri C, Kaiser N, Sasson S. Signaling properties of 4-hydroxyalkenals formed by lipid peroxidation in diabetes. Free Radical Biology and Medicine. 2013 Dec 1;65:978-87. [10.1016/j.freerad biomed.2013.08.163 ] [PMID]
[5] Merecz A, Markiewicz L, Sliwinska A, Kosmalski M, Kasznicki J, Drzewoski J, Majsterek I. Analysis of oxidative DNA damage and its repair in Polish patients with diabetes mellitus type 2: Role in pathogenesis of diabetic neuropathy. Advances in medical sciences. 2015 Sep 1;60(2):220-30. [10.1016/j.advms. 2015.04.001 ] [PMID]
[6] Rains JL, Jain SK. Oxidative stress, insulin signaling, and diabetes. Free Radical Biology and Medicine. 2011 Mar 1;50(5):567-75. [10.1016/j.freeradbiomed.2010.12.006 ] [PMID]
[7] Sexton WJ, Jarow JP. Effect of diabetes mellitus upon male reproductive function. Urology. 1997 Apr 1;49(4):508-13. [10.1016/s0090-4295(96)00573-0 ] [PMID]
[8] Gaunay G, Nagler HM, Stember DS. Reproductive sequelae of diabetes in male patients. Endocrinology and Metabolism Clinics. 2013 Dec 1;42(4):899-914. [10.1016/j.ecl.2013.07.003] [PMID]
[9] Himabindu B, Madhu P, Reddy PS. Diabetes and alcohol: Double jeopardy with regard to oxidative toxicity and sexual dysfunction in adult male Wistar rats. Reproductive Toxicology. 2015 Jan 1;51:57-63. [10.1016/j.reprotox.2014. 12.010 ] [PMID]
[10] Mallidis C, Agbaje I, O'neill J, McClure N. The influence of type 1 diabetes mellitus on spermatogenic gene expression. Fertility and sterility. 2009 Dec 1;92(6):2085-7. [10.1016/j. fertnstert.2009.06.006] [PMID]
[11] Rato L, Alves MG, Duarte AI, Santos MS, Moreira PI, Cavaco JE, Oliveira PF. Testosterone deficiency induced by progressive stages of diabetes mellitus impairs glucose metabolism and favors glycogenesis in mature rat Sertoli cells. The inter-
national journal of biochemistry & cell biology. 2015 Sep 1;66: 1-0. [10.1016/j.biocel.2015.07.001 ] [PMID]
[12] Chandrashekar V, Steger RW, Bartke A, Fadden CT, Kienast SG. Influence of diabetes on the gonadotropin response to the negative feedback effect of testosterone and hypothalamic neurotransmitter turnover in adult male rats. Neuroendo-
crinology. 1991 Apr 4;54(1):30-5. [10.1159/000125847 ] [PMID]
[13] Heydari I, Radi V, Razmjou S, Amiri A. Chronic complications of diabetes mellitus in newly diagnosed patients. International Journal of Diabetes Mellitus. 2010 Apr 1;2(1):61-3. [10.1016/ j.ijdm.2009.08.001]
[14] Cantarovich D, Perrone V. Pancreas transplant as treatment to arrest renal function decline in patients with type 1 diabetes and proteinuria. InSeminars in Nephrology 2012 Sep 1 (Vol. 32, No. 5, pp. 432-436). WB Saunders. [10.1016/j.semnephrol. 2012.07.005 ] [PMID]
[15] Zhao Y, Mazzone T. Human cord blood stem cells and the journey to a cure for type 1 diabetes. Autoimmunity reviews. 2010 Dec 1;10(2):103-7. [10.1016/j.autrev.2010.08.011 ] [PMID]
[16] Srivastava R, Ahmed H, Dixit RK, Saraf SA. Crocus sativus L.: a comprehensive review. Pharmacognosy reviews. 2010 Jul;4(8): 200. [10.4103/0973-7847.70919 ] [PMID]
[17] Vakili A, Eianali MR, Bandegi AR. The protective effects of Saffron against the oxidative damage in a transient model of focal cerebral ischemia in rats. Tehran University Medical Journal. 2011 Oct 1;69(7). [Link]
[18] Bandegi AR, Rashidy-Pour A, Vafaei AA, Ghadrdoost B. Protective effects of Crocus sativus L. extract and crocin against chronic-stress induced oxidative damage of brain, liver and kidneys in rats. Advanced pharmaceutical bulletin. 2014 Dec;4(Suppl 2):493. [10.5681/apb.2014.073] [PMID]
[19] Shirali S, Bathayi SZ, Nakhjavani M, Ashoori MR. Effects of saffron (Crocus sativus L.) aqueous extract on serum biochemical factors in streptozotocin-induced diabetic rats. Iranian journal of medicinal and aromatic plants research. 2012 Jul 22;28(2):293-308. [Link]
[20] Bakhtiary Z, Shahrooz R, Ahmadi A, Malekinejad H, Mostafavi M. Study of protective effects of crocin on testicular histomorphometryand serological parameters incyclopho-
sphamide on treated adult mice. Studies in Medical Sciences. 2014 Sep 10;25(7):663-73. [Link]
[21] Amidi F, Ebrahimi S, Abbasi M, Yazdani M, Ghasemi S. Effects of saffron extract on sperm parameters in rats with experimentally induced varicocele. J Qazvin Univ Med Sci. 2014 Dec 10;18(5):4-11. [Link]
[22] Samadi H, Javadi S, Asri S. Evaluation of the effects of crocin on the serum levels of glucose, insulin, urea, creatinine and β2m in healthy and streptozotocin-induced diabetic rats. Studies in Medical Sciences. 2015 Dec 10;26(9):802-12. [Link]
[23] Yaribeygi H, Mohammadi MT. Protective effect of crocin on kidney performance in chronic uncontrolled hyperglycemia-induced nephropathy in rat. Journal of Zanjan University of Medical Sciences and Health Services. 2017;25(109):36-49. [Link]
[24] Gopumadhavan S, Mohamed R, Venkataranganna MV, Kulkarni KS, Mitra SK. Assessment of ‘Tentex royal’for sexual activity in an experimental model. Indian J Clin Pract. 2003; 13(10):23-6. [] [PMID]
[25] Mokhtari M, Sharifi E, Daneshi A. Effects of hydro-alcoholic extract of red dried stigmas of Crocus sativus L. flowers (saffron) on the levels of pituitary-ovary hormones and folliculogenesis in rats. [10.22074/ijfs.2010.45797] [Link]
[26] Ai J, Nekooeian AA, Takhshid MA, Mostafizi N, Mehrabani D. Effect of aqueous extract of Crocus sativus L.(saffron) stigma on serum levels of gonadotropins and folliculogenesis in adult rats. Journal of Applied Animal Research. 2009 Mar 1;35(1):49. [10.1080/09712119.2009.9706983] [link]
[27] Sadoughi SD, Edalatmanesh MA, Rahbarian R. The Effect of Curcumin on Pituitary-Gonadal Axis, DNA Oxidative Damage
400
Rahbarian R, et al. Effect of Crocin on Pituitary-Testicle Hormonal Axis. JSMJ. 2023; 22(3): 390-400
Jundishapur
Journal of Medical Sciences
July & August 2023. Vol 22. No 3
and Antioxidant Enzymes Activity of Testicular Tissue in Male Diabetic Rats. Journal of Advanced Biomedical Sciences. 2017 Dec 10;7(4):511-20. [Link]
[28] Santos GJ, Oliveira CA, Boschero AC, Rezende LF. CNTF protects MIN6 cells against apoptosis induced by Alloxan and IL-1β through downregulation of the AMPK pathway. Cellular signalling. 2011 Oct 1;23(10):1669-76. [10.1016/j.cellsig.2011. 06.001 ] [PMID]
[29] Oryan A, Hashemnia M, Hamidi AR, Mohammadalipour A. Effects of hydro-ethanol extract of Citrullus colocynthis on blood glucose levels and pathology of organs in alloxan-induced diabetic rats. Asian Pacific journal of tropical disease. 2014 Apr 1;4(2):125-30. [link]
[30] Sadoughi D. Effect of curcumin and low frequency electromagnetic field on the hormones of pituitary-gonad axis in male diabetic rats. Internal Medicine Today. 2017 Jan 10;23(1):27-33. [10.18869/acadpub.hms.23.1.27 ][Link]
[31] Tirabassi G, Chelli FM, Ciommi M, Lenzi A, Balercia G. Influence of the hypothalamic–pituitary–adrenal axis dysregulation on the metabolic profile of patients affected by diabetes mellitus-associated late onset hypogonadism. Nutrition, Metabolism and Cardiovascular Diseases. 2016 Jan 1;26(1):53-9. [10.1016/ j.numecd.2015.10.006.] [PMID]
[32] Hasanzadeh S, Sadrkahnlou RA, Farshid M. 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. 2011 Jul 10;22(3):239-48. [Link]
[33] Shayakhmetova GM, Bondarenko LB, Matvienko AV, Kovalenko VM. Correlation between spermatogenesis disorders and rat testes CYP2E1 mRNA contents under experimental alcoholism or type I diabetes. Advances in medical sciences. 2014 Sep 1;59(2):183-9. [10.1016/j.advms. 2014.03.004 ] [PMID]
[34] Chandrashekar V, Bartke A. The impact of altered insulin-like growth factor-I secretion on the neuroendocrine and testicular functions. Minerva ginecologica. 2005 Feb 1;57(1):87-97. [PMID]
[35] Schoeller EL, Albanna G, Frolova AI, Moley KH. Insulin rescues impaired spermatogenesis via the hypothalamic-pituitary-gonadal axis in Akita diabetic mice and restores male fertility. Diabetes. 2012 Jul 1;61(7):1869-78. [10.2337/db11-1527 ] [PMID]
[36] Jahangiri M, Vaezi G, Hojati V. The Effect of Alcoholic Extract of Kudzu Root on the Sex Hormones of Streptozotocin-induced Diabetic Male Rats. Journal of Animal Biology. 2016 Jul 22;8(4):13-25. [Link] [PMID]
[37] Xi L, Qian Z, Xu G, Zheng S, Sun S, Wen N, Sheng L, Shi Y, Zhang Y. Beneficial impact of crocetin, a carotenoid from saffron, on insulin sensitivity in fructose-fed rats. The Journal of nutritional biochemistry. 2007 Jan 1;18(1):64-72. [10.1016/j.jnutbio. 2006.03.010 ] [PMID]
[38] Sapanidou V, Taitzoglou I, Tsakmakidis Ι, Kourtzelis I, Fletouris D, Theodoridis A, Zervos I, Tsantarliotou M. Antioxidant effect of crocin on bovine sperm quality and in vitro fertilization. Theriogenology. 2015 Nov 1;84(8):1273-82. [10.1016/j.therio genology.2015.07.005 ] [PMID]
[39] Maleki EM, Eimani H, Bigdeli MR, Ebrahimi B, Shahverdi AH,
Narenji AG, Abedi R. A comparative study of saffron aqueous extract and its active ingredient, crocin on the in vitro maturation, in vitro fertilization, and in vitro culture of mouse oocytes. Taiwanese Journal of Obstetrics and Gynecology. 2014 Mar 1;53(1):21-5. [10.1016/j.tjog.2012.11.004 ] [PMID]
[40] Sadoughi S. Effects of crocin on ovarian follicle and serum sex hormone in letrozole-induced polycystic ovarian syndrome in rat model. Journal of Ardabil University of Medical Sciences. 2017 Jul 10;17(2):198-210. [Link]
[41] ABEER AA, NESREN MA, EL-SAWY SA, EL-SAKA MH. The effect of crocin on endocrine functions of the testes before and after testicular damage in rats. The Medical Journal of Cairo University. 2018 Mar 1;86(March):375-82. [Link]
[42] Gül M, Kayhan Kuştepe E, Erdemli ME, Altınöz E, Gözükara Bağ HG, Gül S, Göktürk N. Protective effects of crocin on acrylamide‐induced testis damage. Andrologia. 2021 Oct;53 (9):e14176. [10.1111/and.14176 ] [PMID]