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  • 1 “Iuliu Hatieganu” University of Medicine and Pharmacy, Romania
  • 2 “Constantin Papilian” Military Emergency Hospital, Romania
  • 3 “I. Chiricuta” Oncologic Institute, Romania
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Background

Exposure to high altitude in hypobaric hypoxia (HH) is considered to be a physiological oxidative/nitrosative stress. Quercetin (Que) is an effective antioxidant and free radical scavenger against oxidative/nitrosative stress.

Aims

The aim of this study was to investigate the cardioprotective effects of Que in animals exposed to intermittent HH (IHH) and therefore exposed to oxidative/nitrosative stress.

Materials and methods

Wistar albino male rats were exposed to short-term (2 days) or long-term (4 weeks; 5 days/week) IHH in a hypobaric chamber (5,500 m, 8 h/day, 380 mmHg, 12% O2, and 88% N2). Half of the animals received natural antioxidant Que (body weight: 30 mg/kg) daily before each IHH exposure and the remaining rats received vehicle (carboxymethylcellulose solution). Control rats were kept under normobaric normoxia (Nx) and treated in a corresponding manner. One day after the last exposure to IHH, we measured the cardiac hypoxia-induced oxidative/nitrosative stress biomarkers: the malondialdehyde (MDA) level and protein carbonyl (PC) content, the activity of some antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)], the nitrite plus nitrate (NOx) production, and the inducible nitric oxide synthase (iNOS) protein expression.

Results

Heart tissue MDA and PC levels, NOx level, and iNOS expression of IHH-exposed rats had increased, and SOD and CAT activities had decreased compared with those of the Nx-exposed rats (control groups). MDA, CP, NOx, and iNOS levels had decreased in Que-treated IHH-exposed rats compared with IHH-exposed rats (control groups). However, Que administration increased SOD and CAT activities of the heart tissue in the IHH-exposed rats.

Conclusion

HH exposure increases oxidative/nitrosative stress in heart tissue and Que is an effective cardioprotective agent, which further supports the oxidative cardiac dysfunction induced by hypoxia.

  • 1.

    Aktan F : iNOS-mediated nitric oxide production and its regulation. Life Sci. 75, 639653 (2004)

  • 2.

    Annapurna A , Reddy CS , Akondi RB , Rao SR : Cardioprotective actions of two bioflavonoids, quercetin and rutin, in experimental myocardial infarction in both normal and streptozotocin-induced type I diabetic rats. J. Pharm. Pharmacol. 61, 13651374 (2009)

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

    Bakhshaeshi M , Khaki A , Fathiazad F , Khaki AA , Ghadamkheir E : Anti-oxidative role of quercetin derived from Allium cepa on aldehyde oxidase (OX-LDL) and hepatocytes apoptosis in streptozotocin-induced diabetic rat. Asian Pac. J. Trop. Biomed. 2, 528531 (2012)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Boots AW , Haenen GR , Bast A : Health effects of quercetin: from antioxidant to nutraceutical. Eur. J. Pharmacol. 585, 325337 (2008)

  • 5.

    Chandel NS , Maltepe E , Goldwasser E , Mathieu CE , Simon MC , Schumacker PT : Mitchondrial reactive species trigger hypoxia induced transcription. Proc. Natl. Acad. Sci. U. S. A. 95, 1171511720 (1998)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Chen YW , Chou HC , Lin ST , Chen YH , Chang YJ , Chen L , Chan HL : Cardioprotective effects of quercetin in cardiomyocyte under ischemia/reperfusion injury. Evid. Based Complement. Alternat. Med. 2013, 364519 (2013)

    • Search Google Scholar
    • Export Citation
  • 7.

    Chis IC , Baltaru D , Marton A , Maier M , Muresan A , Clichici S : Effects of quercetin and chronic (training) exercise on oxidative stress status in animals with streptozotocin-induced diabetes. Bull. USAMV-CN Vet. Med. 70, 3139 (2013)

    • Search Google Scholar
    • Export Citation
  • 8.

    Conti M , Morand PC , Levillain P : Improved fluorimetric determination of malonaldehyde. Clin. Chem. 37, 12731275 (1991)

  • 9.

    Daff S : NO synthase: structure and mechanisms. Nitric Oxide 23, 111 (2010)

  • 10.

    Di Naso FC , Simoes Dias A , Porawski M , Marroni NA : Exogenous superoxide dismutase: action on liver oxidative stress in animals with streptozotocin-induced diabetes. Exp. Diab. Res. 2011, 754132 (2011)

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

    Dias AS , Porawski M , Alonso M , Marroni N , Collado PS , González-Gallego J : Quercetin decreases oxidative stress, NF-kappaB activation, and iNOS over expression in liver of streptozotocin-induced diabetic rats. J. Nutr. 135, 22992304 (2005)

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

    Dosek A , Ohmo H , Acs Z , Taylor AW , Radak Z : High altitude and oxidative stress. Respir. Physiol. Neurobiol. 158, 128131 (2007)

  • 13.

    Droge W : Free radicals in the physiological control and cell function. Physiol. Rev. 82, 4795 (2002)

  • 14.

    Dumitrovici A , Bolfa PF , Mureşan A , Maier M , Chiş IC : Short-term versus long-term intermittent hypobaric hypoxia on cardiac fibrosis and cardioprotective effects of natural antioxidants supplementation in rat hearts. Bull. USAMV-CN Vet. Med. 70, 5665 (2013)

    • Search Google Scholar
    • Export Citation
  • 15.

    Dumitrovici A , Chiş IC , Mureşan A , Marton A , Moldovan R , Vlad D , Borza G , Bolfa P : Quercetin, Lycium barbarum and Chitosan reverse the effects of hypobaric hypoxia and exert cardioprotective effects in rats. Fiziologia (Physiology) 23, 1822 (2013)

    • Search Google Scholar
    • Export Citation
  • 16.

    Farías JG , Zepeda AB , Calaf GM : Melatonin protects the heart, lungs and kidneys from oxidative stress under intermittent hypobaric. Biol. Res. 45, 8185 (2012)

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

    Flohe L , Becker R , Brigelius R , Lengfelder E , Ötting F (1990): Convenient assays for superoxide dismutase. In: CRC Handbook of Free Radicals and Antioxidants in Biomedicine, vol III, ed Miquel J, CRC Press, Boca Raton, pp. 287293

    • Search Google Scholar
    • Export Citation
  • 18.

    Formagio ASN , Kassuya CAL , Neto FF , Volobuff CRF , Iriguchi EKK , Vieira M , Foglio MA : The flavonoid content and antiproliferative, hypoglycaemic, anti-inflammatory and free radical scavenging activities of Annona dioica St. Hill. BMC Complement. Altern. Med. 13, 1422 (2013)

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

    Hanasaki Y , Ogawa S , Fukui S : The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic. Biol. Med. 16, 845850 (1994)

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

    Jeong SM , Kang MJ , Choi HN , Kim JH , Kim JI : Quercetin ameliorates hyperglycemia and dyslipidemia and improves antioxidant status in type 2 diabetic db/db mice. Nutr. Res. Pract. 6, 201207 (2012)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Jo HY , Kim Y , Nam SY , Lee BJ , Kim YB , Yun YW , Ahn B : The inhibitory effect of quercetin gallate on iNOS expression induced by lipopolysaccharide in Balb/c mice. J. Vet. Sci. 9, 267272 (2008)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Jung F , Palmer LA , Zhou N , Johns RA : Hypoxic regulation of inducible nitric oxide synthase via hypoxia inducible factor-1 in cardiac myocytes. Circ. Res. 86, 319325 (2000)

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

    Kaluz S , Kaluzova M , Stanbridge EJ : Regulation of gene expression by hypoxia: integration of the HIF-transduced hypoxic signal at the hypoxia-responsive element. Clin. Chim. Acta 395, 613 (2008)

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

    Kanter M , Aktas C , Erboga M : Protective effects of quercetin against apoptosis and oxidative stress in streptozotocin-induced diabetic rat testis. Food Chem. Toxicol. 50, 719725 (2012)

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

    Lee SD , Kuo WW , Wu CH , Lin YM , Lin JA , Lu MC , Yang AL , Liu JY , Wang SG , Liu CJ , Chen LM , Huang CY : Effects of short- and long-term hypobaric hypoxia on Bcl2 family in rat heart. Int. J. Cardiol. 108, 376384 (2006)

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

    Lin YM , Huang SK , Wang HF , Chen LM , Tsai FJ , Hsu HH , Kuo CH , Wang PS , Huang CY , Lee SD : Short-term versus long-term intermittent hypobaric hypoxia on cardiac fibrosis and Fas death receptor dependent apoptotic pathway in rat hearts. Chin. J. Physiol. 51, 308316 (2008)

    • Search Google Scholar
    • Export Citation
  • 27.

    Martinez-Flores S , Gutierez MB , Sanchez-Campos S , Gonzales-Gallego J , Tunon MJ : Quercetin prevents nitric oxide production and nuclear factor kappa B activation in interleukin-1β-activated rat hepatocytes. J. Nutr. 135, 13591365 (2005)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Pippenger CE , Browne RW , Armstrong D (1998): Regulatory antioxidant enzymes. In: Free radical and antioxidant protocols. Methods in molecular biology, vol 108, ed Armstrong D, Humana Press, Totowa, pp. 299313

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

    Reznick AZ , Packer L : Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol. 233, 347357 (1994)

    • Search Google Scholar
    • Export Citation
  • 30.

    Romero RM , Canuelo A , Siles E , Oliver FJ , Lara ME : Nitric oxide modulates hypoxia-inducible factor-1 and poly (ADP-ribose) polymerase-1 cross talk in response to hypobaric hypoxia. J. Appl. Physiol. 112, 816823 (2012)

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

    Rus A , Peinado MA , Castro L , Del Moral MI : Lung eNOS and iNOS are reoxygenation time-dependent upregulated after acute hypoxia. Anat. Rec. (Hoboken) 293, 10891098 (2010)

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

    Sarkar A , Angeline MS , Anand K , Ambasta RK , Kumar P : Naringenin and quercetin reverse the effect of hypobaric hypoxia and elicit neuroprotective response in the murine model. Brain Res. 24, 5970 (2012)

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

    Singh M , Thomas P , Shukla D , Tulsawani R , Saxena S , Bansal A : Effect of subchronic hypobaric hypoxia on oxidative stress in rat heart. Appl. Biochem. Biotechnol. 169, 24052019 (2013)

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

    Tang D , Dong Y , Ren H , Li L , He C : A review of phytochemistry, metabolite changes, and medicinal uses of the common food mung bean and its sprouts (Vigna radiata). Chem. Cent. J. 8, 4 (2014)

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

    Titherage MA (1998): The enzymatic measurement of nitrate and nitrite. In: Nitric oxide protocols. Methods in molecular biology, vol 100, ed Titherage MA, Humana Press, Totowa, pp. 8391

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

    Wang ZH , Cai XL , Wu L , Yu Z , Liu JL , Zhou ZN , Liu J , Yang HT : Mitochondrial energy metabolism plays a critical role in the cardioprotection afforded by intermittent hypobaric hypoxia. Exp. Physiol. 97, 11051118 (2012)

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

    Wang ZH , Chen YX , Zhang CM , Wu L , Yu Z , Cai XL , Guan Y , Zhou ZN , Yang HT : Intermittent hypobaric hypoxia improves postischemic recovery of myocardial contractile function via redox signaling during early reperfusion. Am. J. Physiol. Heart. Circ. Physiol. 301, 169516705 (2011)

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

    Zhang Y , Yang HT , Zhou ZN : Cardioprotection of intermittent hypoxia. Acta Physiol. Sin. 59, 601613 (2007)

  • 39.

    Zhang Y , Zhong N , Zhou ZN : Effects of chronic intermittent hypobaric hypoxia on the L-type calcium current in rat ventricular myocytes. High Alt. Med. Biol. 11, 6167 (2011)

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

    Zhong N , Zhang Y , Zhu HF , Wang JC , Fang QZ , Zhou ZN : Myocardial capillary angiogenesis and coronary flow in ischemia tolerance rat by adaptation to intermittent high altitude hypoxia. Acta Pharmacol. Sin. 23, 305310 (2002)

    • Search Google Scholar
    • Export Citation
  • 41.

    Xie QW , Kashiwabara Y , Nathan C : Role of transcription factor NF-κB/Rel in induction of nitric oxide synthase. J. Biol. Chem. 269, 47054708 (1994)

    • Search Google Scholar
    • Export Citation
  • 42.

    Yin X , Zheng Y , Liu Q , Cai J , Cai L : Cardiac response to chronic intermittent hypoxia with a transition from adaptation to maladaptation: the role of hydrogen peroxide. Oxid. Med. Cell. Longev. 2012, 569520 (2012)

    • Crossref
    • Search Google Scholar
    • Export Citation

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