Effects of crocin and zinc chloride on blood levels of zinc and metabolic and oxidative parameters in streptozotocin-induced diabetic rats

Document Type : Original Research Article


1 Division of Clinical Pathology, Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, I.R. Iran

2 Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, I.R. Iran


Objectives:Crocin is one of constituents of saffron and has antioxidant property. Zinc chloride is one of the common compounds of zinc with antioxidant activity. The present study was aimed to investigate separate and combined treatment effects of crocin and zinc chloride on blood levels of zinc and metabolic and oxidative parameters in diabetic rats.
Materials and Methods:Diabetes was induced by intraperitoneal (i.p.) injection of 50 mg/kg of streptozotocin (STZ) and was confirmed by blood glucose levels higher than 250 mg/dL. After confirmation of diabetes, injections (i.p.) of crocin and zinc chloride were performed for six weeks. At the end of the experiment, blood levels of zinc, glucose, insulin, malodialdehyde (MDA), and total antioxidant capacity (TAC) were measured. ‎
Results:Crocin (25 and 50 mg/kg) and zinc chloride (5 mg/kg) significantly recovered the decreased levels of zinc, insulin, and TAC and improved the increased levels of glucose and MDA in STZ-induced diabetic rats. In a combination treatment performed with an ineffective dose of crocin (12.5 mg/kg) and a low dose of zinc chloride (1.25 mg/kg), improving effects were observed on the above-mentioned biochemical parameters.‎
Conclusions: The results indicated that separate and combined treatments with crocin and zinc chloride produced improving effects on the blood levels of zinc, glucose, insulin, MDA and TAC in STZ-induced diabetic rats.‎


Main Subjects

Abou-Seif MA, Youssef AA. 2004. Evaluation of some biochemical changes in diabetic patients. ClinChimActa, 346: 161-170.
Aly HF, Mantawy MM. 2012. Comparative effects of zinc, selenium and vitamin E or their combination on carbohydrate metabolizing enzymes and oxidative stress in streptozotocine-induced diabetic rats.Eur Rev Med PharmacolSci, 16: 66-78.
Benzie IF, Strain JJ. 1996. The ferric reducing ability of plasma (FRAP) as a measure of antioxidant power: The FRAP assay. Anal Biochem, 239: 70-76.
Bicer M, Akil M, Sivrikaya A, Kara E, Baltaci, AK, Mogulkoc R. 2011. Effects of zinc supplementation on the distribution of various elements in the serum of diabetic rats subjected to an acute swimming exercise. J PhysiolBiochem, 67: 511-517.
Bluestone JA, Herold K, Eisenbarth GS. 2010. Genetic, pathogenesis and clinical intervention in type 1 diabetes. Nature, 464: 1293-1300.
Chausmer AB. 1998. Zinc, insulin and diabetes. J Am CollNutr, 17: 109-115.
DiSilvestro RA. Zinc in relation to diabetes and oxidative disease. J Nutr 2000; 130: 1509S-15011S.
Farshid AA, Tamaddonfard E, Simaee N, Mansouri S, Najafi S, Asri-Rezaee S, Alavi H. 2013. Effects of histidine and n-acetylcysteine on doxorubicin-induced cardiomyopathy in rats.CardiovascToxicol,  DOI: 10.1007/s12012-013-9239-6.
Hosseinzadeh H, Nassiri-Asl M. 2013. Avicenna̕ s (Ibn Sina) the canon of medicine and saffron (Crocus sativus): a review. Phytother Res, 27: 475-483.
Islam MS, Loots du T. 2009. Experimental rodent models of type 2 diabetes: a review. Methods Find ExpClinPharmacol, 31: 249-261.
Karami M, Bathaie SZ, Tiraihi T, Habibi-Rezaei M, Arabkheradmand J, Faghihzadeh S. 2013. Crocin improved locomotor function and mechanical behavior in the rat model of contused spinal cord injury through decreasing calcitonin gene related peptide (CGRP). Phytomedicine, 21: 62-67.
Kiilerich S, Christensen MS, Naestoft J, Christainsen C. 1980. Determination of zinc in serum and urine by atomic absorption spectrophotometry: relationship between serum levels of zinc and protein in 104 normal subjects. Clin Chim Acta, 105: 231-39.
King AJ. 2012. The use of animal models in diabetic research. Br J Pharmacol, 166: 877-894.
Lee IA, Lee JH, Baek NI, Kim DH. 2005. Antihyperlipidemic effect of crocin isolated from the fructus of Gardenia jasminoides and its metabolite crocetin. Biol Pharm Bull, 28: 2106-2110.
Li YV. 2014. Zinc and insulin in pancreatic beta-cells. Endocrine, 45: 178-189.
Lin CC, Huang HH, Hu CW, Chen BH, Cheng IW, Chao YY, Huang YL. 2014. Trace elements, oxidative stress and glycemic control in young people with type 1 diabetes mellitus. J Trace Elem Med Biol, 28: 18-22.
Miao X, Sun W, Fu Y, Miao L, Cai L. 2013. Zinc homeostasis in the metabolic syndrome and diabetes. Front Med, 7: 31-52.
Moore K, Roberts LJ. 1998. Measurement of lipid peroxidation. Free Radical Res, 28: 659-671.
Navarro-Alarcan M, Ruiz-Ojeda FJ, Blanca-Herrera RM, Agil A. 2013. Antioxidant activity of melatonin in diabetes in relation to the regulation and levels of plasma Cu, Zn, Fe, Mn, and Se in Zucker diabetic rats. Nutrition, 29: 785-789.
Niedowicz DM, Daleke DL. 2005. The role of oxidative stress in diabetic complications. Cell BiochemBiophys, 43: 289-330.
Ozcelik D, Tuncdemir M, Ozturk M, Uzun H. 2011. Evaluation of trace elements and oxidative stress in the liver and kidney of streptozotocin-induced experimrntal diabetic rat model. Gen PhysiolBiophys, 30: 356-363.
Patel DK, Kumar R, Laloo D, Hemalatha S. 2012a. Diabetes mellitus: an overview on its pharmacological aspects and reported medicinal plants having antidiabetic activity. Asian Pac J Trop Biomed, 2: 411-420.
Patel DK, Prasad SK, Kumar R, Hemalatha S. 2012b. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pac J Trop Biomed, 2: 320-330.
Poma A, Fontecchio G, Carlucci G, Chichiricco G. 2012. Anti-inflammatory properties of drugs from saffron crocus.AntiinflammAntiallergy Agents Med Chem, 11: 37-51.
Prasad AS. 2009. Zinc: role in immunity, oxidative stress and chronic inflammation. Cur OpinClinNutr Care, 12: 646-652.
Pushparani DS, Nirmala S, Theagarayan P. 2013. Low serum level vitamin C and zinc is associated with the development of oxidative stress in type 2 diabetes mellitus with periodontitis. Int J Pharm Rev Res, 23: 259-264.
Rajaei Z, Hadjzadeh MA, Nemati H, Hosseini M, Ahmadi M, Shafiee S. 2013. Antihyperglycemic and antioxidant activity of crocin in streptozotocin-induced diabetic rats. J Med Food, 16: 206-210.
Shirali S, Zahra Bathaie S, Nakhjavani M. 2013. Effect of crocin on the insulin resistance and lipid profile of stereptozotocin-induced diabetic rats.Phytother Res, 27: 1042-1047.
Szkudelski T. 2001. The mechanisms of alloxan and streptozotocin action in B cells of the rat pancreas.Physiol Res, 50: 536-546.
Tamaddonfard E, Farshid AA, Ahmadian E, Hamidhoseyni A. 2013a. Crocin enhanced functional recovery after sciatic nerve crush injury in rats. Iran J Basic Med Sci, 16: 83-90.
Tamaddonfard E, Farshid AA, Asri-Rezaee S, Javadi Sh, Khosravi V, Rahman B, Mirfakhraee Z. 2013b.Crocin improved learning and memory impairment in streptozotocin-induced diabetic rats. Iran J Basic Med Sci, 16: 91-100.
Tamaddonfard E, Farshid AA, Eghdami K, Samadi F, Erfanparast E. 2013c. Comparison of the effects of crocin, safranal and diclofenac on local inflammation and inflammatory pain responses induced by carrageenan in rats.Pharmacol Rep, 65: 1272-1280.
Tamaddonfard E, Farshid AA, Hosseini L. 2012a. Crocin alleviates the local paw edema induced by histamine in rats. Avicenna J Phytomedicine, 2: 97-104.
Tamaddonfard E, HamzehGooshch N, Seiednejad-Yamchi S. 2012b.Central effect of crocin on penicillin-induced epileptiform activity in rats.Pharmacol Rep, 64: 94-101.
Tamaddonfard E, Hamzeh-Gooshchi N. 2010a. Effect of crocin on the morphine-induced antinociception in the formalin test in rats.Phytother Res, 24: 410-413.
Tamaddonfard E, Hamzeh-Gooshchi N. 2010b Effects of intraperitoneal and intracerebroventricular injection of crocin on acute corneal pain in rats.Phytother Res, 24: 1463-1467.
Triggiani V, Resta F, Guastamacchia E, Sabba C, Licchelli B, Ghiyasaldin S, Tafaro E. 2006. Role of antioxidants, essential fatty acids, carnitine, vitamins, phytochemicals and trace elements in the treatment of diabetes mellitus and its chronic complications. EndocrMetab Immune Disord Drug targets, 6: 77-93.
Tudor R, Zalewiski PD, Ratnaik RN. 2005. Zinc in health and chronic disease. J Nutr Health Aging, 9: 45-51.
Umrani RD, Agrawal DS, Paknikar KM. 2013. Anti-diabetic activity and safety assessment of Ayurvedic medicine, Jasadabhasma (zinc ash) in rats. Indian J ExpBiol, 51: 811-822.
Vallee BL, Falchuk KH. 1993. The biochemical basis of zinc physiology. Physiol Rev, 73: 79-118.
Vardatsikos G, Pandey NR, Srivastava AK. 2013. Insulino-mimetic and anti-diabetic effects of zinc. J InorgBiochem, 120: 8-17.
Wild S, Roglic G, Green A, Sicree R, King H. 2004. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care, 27: 1047-1053.
Yagi K. 1984. Assay for blood plasma or     serum. Methods Enzymol, 105: 328-331.
Yu BP. 1994. Cellular defense against damage from reactive oxygen species.Physiol Rev, 74: 139-162.
Zhang Z, Wang CZ, Wen XD, Shoyama Y, Yuan CS. 2013.Role of saffron and its constituents on cancer chemoprevention. Pharm Biol, 51: 920-924.
Zhu K, Nie S, Li C, Huang J, Hu X, Li W, Gong D, Xie M. 2013. Antidiabetic and pancreatic-protective effects of zinc threoninate chelate in diabetic rats may be associated with its antioxidant stress ability. Biol Trace Elem Res, 153: 291-298.