View More View Less
  • 1 Tabriz University of Medical Sciences, Iran
  • 2 Tabriz University of Medical Sciences, Iran
  • 3 Tabriz University of Medical Sciences, Iran
Restricted access

Purchase article

USD  $25.00

1 year subscription (Individual Only)

USD  $752.00

Background

Oxidative stress plays a critical role in the pathogenesis and progression of type 2 diabetes and diabetic-associated cardiovascular complications. This study investigated the impact of crocin combined with voluntary exercise on heart oxidative stress indicator in high-fat diet-induced type 2 diabetic rats.

Materials and methods

Rats were divided into four groups: diabetes, diabetic-crocin, diabetic-voluntary exercise, diabetic-crocin-voluntary exercise. Type 2 diabetes was induced by high-fat diet (4 weeks) and injection of streptozotocin (intraperitoneally, 35 mg/kg). Animals received crocin orally (50 mg/kg); voluntary exercise was performed alone or combined with crocin treatment for 8 weeks. Finally, malondialdehyde (MDA), activity of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured spectrophotometrically.

Results

Treatment of diabetic rats with crocin and exercise significantly decreased the levels of MDA (p < 0.001) and increased the activity of SOD, GPx, and CAT compared with the untreated diabetic group. In addition, combination of exercise and crocin amplified their effect on antioxidant levels in the heart tissue of type 2 diabetic rats.

Conclusion

We suggest that a combination of crocin with voluntary exercise treatment may cause more beneficial effects in antioxidant defense system of heart tissues than the use of crocin or voluntary exercise alone.

  • 1.

    Aebi H : Catalase in vitro. Methods Enzymol. 105, 121126 (1984)

  • 2.

    Al-awar A , Kupai K , Veszelka M , Szűcs G , Attieh Z , Murlasits Z , Török S , Pósa A , Varga C : Experimental diabetes mellitus in different animal models. J. Diabetes Res. 2016, 9051426 (2016)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Altinoz E , Oner Z , Elbe H , Turkoz Y , Cigremis Y : Protective effect of saffron (its active constituent, crocin) on oxidative stress and hepatic injury in streptozotocin induced diabetic rats. Gene Ther. Mol. Biol. 16, 160171 (2014)

    • Search Google Scholar
    • Export Citation
  • 4.

    Ashour M , Salem S , Hassaneen H , El-Gadban H , Elwan N , Awad A , Basu TK : Antioxidant status and insulin-dependent diabetes mellitus (IDDM). J. Clin. Biochem. Nutr. 26, 99107 (1999)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Asri-Rezaei S , Tamaddonfard E , Ghasemsoltani-Momtaz B , Erfanparast A , Gholamalipour S : Effects of crocin and zinc chloride on blood levels of zinc and metabolic and oxidative parameters in streptozotocin-induced diabetic rats. Avicenna J. Phytomed. 5, 403 (2015)

    • Search Google Scholar
    • Export Citation
  • 6.

    Assimopoulou A , Sinakos Z , Papageorgiou V : Radical scavenging activity of Crocus sativus L. Extract and its bioactive constituents. Phytother. Res. 19, 9971000 (2005)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Badalzadeh R , Yavari R , Chalabiani D : Mitochondrial ATP-sensitive K+ channels mediate the antioxidative influence of diosgenin on myocardial reperfusion injury in rat hearts. Gen. Physiol. Biophys. 34, 323329 (2015)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Brocardo PS , Boehme F , Patten A , Cox A , Gil-Mohapel J , Christie BR : Anxiety- and depression-like behaviors are accompanied by an increase in oxidative stress in a rat model of fetal alcohol spectrum disorders: protective effects of voluntary physical exercise. Neuropharmacology 62, 16071618 (2012)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Brownlee M : Biochemistry and molecular cell biology of diabetic complications. Nature 414, 813820 (2001)

  • 10.

    Busik JV , Mohr S , Grant MB : Hyperglycemia-induced reactive oxygen species toxicity to endothelial cells is dependent on paracrine mediators. Diabetes 57, 19521965 (2008)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Eddouks M , Maghrani M , Lemhadri A , Ouahidi M-L , Jouad H : Ethnopharmacological survey of medicinal plants used for the treatment of diabetes mellitus, hypertension and cardiac diseases in the south-east region of morocco (tafilalet). J. Ethnopharmacol. 82, 97103 (2002)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Ellison GM , Waring CD , Vicinanza C , Torella D : Physiological cardiac remodelling in response to endurance exercise training: cellular and molecular mechanisms. Heart 98, 510 (2011)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Evans JL , Goldfine ID , Maddux BA , Grodsky GM : Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr. Rev. 23, 599622 (2002)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Fraga CG , Leibovitz BE , Tappel AL : Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: characterization and comparison with homogenates and microsomes. Free Radic. Biol. Med. 4, 155161 (1988)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Fubini B , Hubbard A : Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis. Free Radic. Biol. Med. 34, 15071516 (2003)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Ghorbanzadeh V , Mohammadi M , Dariushnejad H , Chodari L , Mohaddes G : Effects of crocin and voluntary exercise, alone or combined, on heart VEGF-A and HOMA-IR of HFD/STZ induced type 2 diabetic rats. J. Endocrinol. Invest. 39, 11791186 (2016)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Giannuzzi P , Temporelli PL , Corrà U , Tavazzi L , Group E-CS: Antiremodeling effect of long-term exercise training in patients with stable chronic heart failure results of the exercise in left ventricular dysfunction and chronic heart failure (ELVD-CHF) trial. Circulation 108, 554559 (2003)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Goyal S , Arora S , Sharma A , Joshi S , Ray R , Bhatia J , Kumari S , Arya D : Preventive effect of crocin of Crocus sativus on hemodynamic, biochemical, histopathological and ultrastuctural alterations in isoproterenol-induced cardiotoxicity in rats. Phytomedicine 17, 227232 (2010)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    He S-Y , Qian Z-Y , Tang F-T , Wen N , Xu G-L , Sheng L : Effect of crocin on experimental atherosclerosis in quails and its mechanisms. Life Sci. 77, 907921 (2005)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Hilberg T : Physical activity in the prevention of cardiovascular diseases-epidemiology and mechanisms. Hämostaseologie 28, 915 (2008)

    • Search Google Scholar
    • Export Citation
  • 21.

    Hosseinzadeh H , Sadeghnia HR , Ziaee T , Danaee A : Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemia-reperfusion-induced oxidative damage in rats. J. Pharm. Pharm. Sci. 8, 387393 (2005)

    • Search Google Scholar
    • Export Citation
  • 22.

    Hosseinzadeh H , Younesi HM : Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol. 2, 7 (2002)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Huang W , Glass CK : Nuclear receptors and inflammation control: molecular mechanisms and pathophysiological relevance. Arterioscler. Thromb. Vasc. Biol. 30, 15421549 (2010)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Ishikawa Y , Gohda T , Tanimoto M , Omote K , Furukawa M , Yamaguchi S , Murakoshi M , Hagiwara S , Horikoshi S , Funabiki K , Tomino Y : Effect of exercise on kidney function, oxidative stress, and inflammation in type 2 diabetic Kk-A(y) mice. Exp. Diabetes Res. 2012, 702948 (2012)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Ke Z , Yip SP , Li L , Zheng X-X , Tong K-Y : The effects of voluntary, involuntary, and forced exercises on brain-derived neurotrophic factor and motor function recovery: a rat brain ischemia model. PLoS One 6, e16643 (2011)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Kupai K , Szabó R , Veszelka M , Al Awar A , Török S , Csonka A , Baráth Z , Pósa A , Varga C : Consequences of exercising on ischemia–reperfusion injury in type 2 diabetic Goto–Kakizaki rat hearts: role of the HO/NOS system. Diabetol. Metab. Syndr. 7, 85 (2015)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Laakso M : Cardiovascular disease in type 2 diabetes: challenge for treatment and prevention. J. Intern. Med. 249, 225235 (2001)

  • 28.

    Lakka TA , Venalainen JM , Rauramaa R , Salonen R , Tuomilehto J , Salonen JT : Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction in men. N. Engl. J. Med. 330, 15491554 (1994)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Lee S , Park Y , Zhang C : Exercise training prevents coronary endothelial dysfunction in type 2 diabetic mice. Am. J. Biomed. Sci. 3, 241252 (2011)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    Leonardo-Mendonça RC , Concepción-Huertas M , Guerra-Hernández E , Zabala M , Escames G , Acuña-Castroviejo D : Redox status and antioxidant response in professional cyclists during training. Eur. J. Sport Sci. 14, 830838 (2014)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Mashmoul M , Azlan A , Yusof BNM , Khaza’ai H , Mohtarrudin N , Boroushaki MT : Effects of saffron extract and crocin on anthropometrical, nutritional and lipid profile parameters of rats fed a high fat diet. J. Funct. Foods 8, 180187 (2014)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32.

    Pari L , Monisha P , Jalaludeen AM : Beneficial role of diosgenin on oxidative stress in aorta of streptozotocin induced diabetic rats. Eur. J. Pharmacol. 691, 143150 (2012)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Roberts CK , Won D , Pruthi S , Barnard RJ : Effect of a diet and exercise intervention on oxidative stress, inflammation and monocyte adhesion in diabetic men. Diabetes Res. Clin. Pract. 73, 249259 (2006)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34.

    Rosa CM , Xavier NP , Henrique Campos D , Fernandes A , Cezar M , Martinez PF , Cicogna AC , Gimenes C , Gimenes R , Okoshi MP : Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats. Cardiovasc. Diabetol. 12, 152 (2013)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35.

    Samarghandian S , Borji A , Delkhosh MB , Samini F : Safranal treatment improves hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats. J. Pharm. Pharm. Sci. 16, 352362 (2013)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36.

    Santini SA , Marra G , Giardina B , Cotroneo P , Mordente A , Martorana GE , Manto A , Ghirlanda G : Defective plasma antioxidant defenses and enhanced susceptibility to lipid peroxidation in uncomplicated IDDM. Diabetes 46, 18531858 (1997)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    Srinivasan K , Viswanad B , Asrat L , Kaul C , Ramarao P : Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol. Res. 52, 313320 (2005)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Timmerman KL , Flynn MG , Coen PM , Markofski MM , Pence BD : Exercise training-induced lowering of inflammatory (CD14+CD16+) monocytes: a role in the anti-inflammatory influence of exercise? J. Leukoc. Biol. 84, 12711278 (2008)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39.

    Tsalouhidou S , Petridou A , Mougios V : Effect of chronic exercise on DNA fragmentation and on lipid profiles in rat skeletal muscle. Exp. Physiol. 94, 362370 (2009)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40.

    Watanabe K , Thandavarayan RA , Harima M , Sari FR , Gurusamy N , Veeraveedu PT , Mito S , Arozal W , Sukumaran V , Prasath Laksmanan A : Role of differential signaling pathways and oxidative stress in diabetic cardiomyopathy. Curr Cardiol. Rev. 6, 280290 (2010)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41.

    Wisløff U , Støylen A , Loennechen JP , Bruvold M , Rognmo Ø , Haram PM , Tjønna AE , Helgerud J , Slørdahl SA , Lee SJ : Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients a randomized study. Circulation 115, 30863094 (2007)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42.

    Wycherley T , Brinkworth G , Noakes M , Buckley J , Clifton P : Effect of caloric restriction with and without exercise training on oxidative stress and endothelial function in obese subjects with type 2 diabetes. Diabetes Obes. Metab. 10, 10621073 (2008)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43.

    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. J. Nutr. Biochem. 18, 6472 (2007)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44.

    Yang H , Jin X , Lam K , Wai C , Yan S-K : Oxidative stress and diabetes mellitus. Clin. Chem. Lab. Med. 49, 17731782 (2011)

  • 45.

    Yang Y-C , Hwang J-H , Hong S-J , Hsu H-K : Enhancement of glucose uptake in 3T3-L1 adipocytes by Toona sinensis leaf extract. Kaohsiung J. Med. Sci. 19, 327332 (2003)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 46.

    Youn J-Y , Park H-Y , Cho K-H : Anti-hyperglycemic activity of Commelina communis L.: inhibition of α-glucosidase. Diabetes Res. Clin. Pract. 66, S149S155 (2004)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47.

    Zhang M , Lv X-Y , Li J , Xu Z-G , Chen L : The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Exp. Diabetes Res. 2008, 704045 (2009)

    • Search Google Scholar
    • Export Citation
  • 48.

    Zheng Y-Q , Liu J-X , Wang J-N , Xu L : Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Res. 1138, 8694 (2007)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 49.

    Zimmet PZ , McCarty DJ , de Courten MP : The global epidemiology of non-insulin-dependent diabetes mellitus and the metabolic syndrome. J. Diabetes Complications 11, 6068 (1997)

    • Crossref
    • Search Google Scholar
    • Export Citation