Potential beneficial effects of oral administration of isoflavones in patients with chronic mountain sickness

Cui,Jianhua; Gao,Liang; Yang,Haijun; Wang,Fuling; Jiang,Chunhua; Gao,Yuqi

doi:10.3892/etm.2013.1388

Potential beneficial effects of oral administration of isoflavones in patients with chronic mountain sickness

Authors:
- Jianhua Cui
- Liang Gao
- Haijun Yang
- Fuling Wang
- Chunhua Jiang
- Yuqi Gao
View Affiliations

Affiliations: Research Center of PLA for Prevention and Treatment of High Mountain Sickness, The 18th Hospital of PLA, Yecheng, Xinjiang 844900, P.R. China, Department of Pathophysiology and High Altitude Physiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
Published online on: November 7, 2013 https://doi.org/10.3892/etm.2013.1388
Pages: 275-279

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Soy isoflavones (Ifs), which are natural phytoestrogens, have beneficial effects in cardiovascular disease. We have previously shown that genistein, the most active component of Ifs, inhibits pulmonary vascular structural remodeling and right ventricular hypertrophy induced by chronic hypoxia in male Wistar rats. This study aimed to evaluate the effects of Ifs on right ventricular and pulmonary hemodynamics in individuals with chronic mountain sickness (CMS). Twenty‑eight male patients living on the Qinghai‑Tibetan plateau (5,200 m) who were suffering from CMS were treated orally with Ifs (20 mg, twice daily) for 45 days. Physiological and plasma biochemical indices, hematology and echocardiography were investigated. It was observed that 45 days of treatment with Ifs significantly increased blood oxygen saturation and markedly decreased the CMS score and heart rate (all P<0.05) of the subjects. Following treatment with Ifs, hematocrit (P<0.05), hemoglobin concentration (P<0.01) and plasma levels of malondialdehyde (P<0.05) were significantly decreased, while plasma levels of nitric oxide (P<0.01) and the plasma activity of nitric oxide synthase (P<0.01) and superoxide dismutase (P<0.01) were markedly increased compared with the respective values obtained prior to treatment with Ifs. The echocardiography results showed that Ifs significantly decreased the main pulmonary artery diameter (P<0.05), right ventricular end‑diastolic anteroposterior diameter (P<0.01), right ventricular end‑diastolic trans diameter (P<0.01), right ventricular anterior wall (P<0.01) and right ventricular outflow tract (P<0.01). These results indicate the potential beneficial effects of Ifs in the reduction of excessive erythrocytosis, the alleviation of oxidative damage and the amelioration of right ventricular index and pulmonary hemodynamics in CMS.

View Figures

View References

1	Monge CC: Chronic mountain sickness. Physiol Rev. 23:166–184. 1943.
2	León-Velarde F, Maggiorini M, Reeves JT, et al: Consensus statement on chronic and subacute high altitude diseases. High Alt Med Biol. 6:147–157. 2005.PubMed/NCBI
3	Penaloza D and Arias-Stella J: The heart and pulmonary circulation at high altitudes: healthy highlanders and chronic mountain sickness. Circulation. 115:1132–1146. 2007. View Article : Google Scholar : PubMed/NCBI
4	Gao Y: High Altitude Military Medicine. Chongqing Publishing House; Chongqing: 2005
5	Wood S, Norboo T, Lilly M, Yoneda K and Eldridge M: Cardiopulmonary function in high altitude residents of Ladakh. High Alt Med Biol. 4:445–454. 2003. View Article : Google Scholar : PubMed/NCBI
6	Wu TY: Chronic mountain sickness on the Qinghai-Tibetan plateau. Chin Med J (Engl). 118:161–168. 2005.PubMed/NCBI
7	Monge CC, Arrequi A and León-Velarde F: Pathophysiology and epidemiology of chronic mountain sickness. Int J Sports Med. 13(Suppl 1): S79–S81. 1992. View Article : Google Scholar : PubMed/NCBI
8	Beall CM, Brittenham GM, Macuaga F and Barragan M: Variation in hemoglobin concentration among samples of high-altitude natives in the Andes and the Himalayas. Am J Hum Biol. 2:639–651. 1990. View Article : Google Scholar
9	Wu T, Wang X, Wei C, et al: Hemoglobin levels in Qinghai-Tibet: different effects of gender for Tibetans vs. Han J Appl Physiol. 98:598–604. 2005. View Article : Google Scholar : PubMed/NCBI
10	Kryger M, McCullough RE, Collins D, Scoggin CH, Weil JV and Grover RF: Treatment of excessive polycythemia of high altitude with respiratory stimulant drugs. Am Rev Respir Dis. 117:455–464. 1978.PubMed/NCBI
11	Vargas M, Leon-Velarde F, Monge CC, Orozco E and Rey L: Enalapril in the treatment of chronic mountain sickness. Wilderness Environ Med. 7:193–194. 1996. View Article : Google Scholar : PubMed/NCBI
12	Plata R, Cornejo A, Arratia C, et al; Commission on Global Advancement of Nephrology (COMGAN), Research Subcommittee of the International Society of Nephrology. Angiotensin-converting-enzyme inhibition therapy in altitude polycythaemia: a prospective randomised trial. Lancet. 359:663–666. 2002. View Article : Google Scholar : PubMed/NCBI
13	Pelouch V, Kolár F, Ost'ádal B, Milerová M, Cihák R and Widimský J: Regression of chronic hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and fibrosis: effect of enalapril. Cardiovasc Drugs Ther. 11:177–185. 1997. View Article : Google Scholar : PubMed/NCBI
14	Richalet JP, Rivera-Ch M, Maignan M, et al: Acetazolamide for Monge's disease: efficiency and tolerance of 6-month treatment. Am J Respir Crit Care Med. 177:1370–1376. 2008.PubMed/NCBI
15	Li P, Huang J, Tian HJ, Huang QY, Jiang CH and Gao YQ: Regulation of bone marrow hematopoietic stem cell is involved in high-altitude erythrocytosis. Exp Hematol. 39:37–46. 2011. View Article : Google Scholar : PubMed/NCBI
16	Gonzales GF, Gasco M, Tapia V and Gonzales-Castañeda C: High serum testosterone levels are associated with excessive erythrocytosis of chronic mountain sickness in men. Am J Physiol Endocrinol Metab. 296:E1319–E1325. 2009. View Article : Google Scholar : PubMed/NCBI
17	Gonzales GF, Tapia V, Gasco M, Rubio J and Gonzales-Castañeda C: High serum zinc and serum testosterone levels were associated with excessive erythrocytosis in men at high altitudes. Endocrine. 40:472–480. 2011. View Article : Google Scholar : PubMed/NCBI
18	Bailey DM, Dehnert C, Luks AM, et al: High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability. J Physiol. 588:4837–4847. 2010. View Article : Google Scholar : PubMed/NCBI
19	Liggins J, Bluck LJ, Runswick S, Atkinson C, Coward WA and Bingham SA: Daidzein and genistein content of fruits and nuts. J Nutr Biochem. 11:326–331. 2000. View Article : Google Scholar : PubMed/NCBI
20	Gencel VB, Benjamin MM, Bahou SN and Khalil RA: Vascular effects of phytoestrogens and alternative menopausal hormone therapy in cardiovascular disease. Mini Rev Med Chem. 12:149–174. 2012. View Article : Google Scholar : PubMed/NCBI
21	Hall WL, Formanuik NL, Harnpanich D, et al: A meal enriched with soy isoflavones increases nitric oxide-mediated vasodilation in healthy postmenopausal women. J Nutr. 138:1288–1292. 2008.PubMed/NCBI
22	Kim H, Lee MJ, Kim JE, Park SD, Moon HI and Park WH: Genistein suppresses tumor necrosis factor-alpha-induced proliferation via the apoptotic signaling pathway in human aortic smooth muscle cells. J Agric Food Chem. 58:2015–2019. 2010. View Article : Google Scholar
23	Vera R, Galisteo M, Villar IC, et al: Soy isoflavones improve endothelial function in spontaneously hypertensive rats in an estrogen-independent manner: role of nitric-oxide synthase, superoxide, and cyclooxygenase metabolites. J Pharmacol Exp Ther. 314:1300–1309. 2005. View Article : Google Scholar
24	Li X, Gao Z, Liu F, Xiang D, Jiang C and Huang Q: The preventive effects of phytoestrogen on chronic hypoxic pulmonary hypertension in rats. Chinese Pharm Bull. 20:897–900. 2004.(In Chinese).
25	Li X, Gao Z, Liu F, Jiang C, Xiang D and Huang Q: The effects of genistein on pulmonary vascular structural remodeling induced by chronic hypoxia. Chinese Pharml Bull. 20:1257–1261. 2004.(In Chinese).
26	Li X, Gao Y, Liu F, et al: The regulative effects of genistein on vascular active factors in chronic hypoxic rats. Food Sci. 20(10): 219–223. 2005.(In Chinese).
27	Allemann Y, Sartori C, Lepori M, et al: Echocardiographic and invasive measurements of pulmonary artery pressure correlate closely at high altitude. Am J Physiol Heart Circ Physiol. 279:H2013–H2016. 2000.PubMed/NCBI
28	Hamilton-Reeves JM, Vazquez G, Duval SJ, Phipps WR, Kurzer MS and Messina MJ: Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis. Fertil Steril. 94:997–1007. 2010. View Article : Google Scholar : PubMed/NCBI
29	Scherrer U, Vollenweider L, Delabays A, et al: Inhaled nitric oxide for high-altitude pulmonary edema. N Engl J Med. 334:624–629. 1996. View Article : Google Scholar : PubMed/NCBI
30	Hoit BD, Dalton ND, Erzurum SC, Laskowski D, Strohl KP and Beall CM: Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders. J Appl Physiol. 99:1796–1801. 2005. View Article : Google Scholar : PubMed/NCBI
31	Ge RL, Mo VY, Januzzi JL, et al: B-type natriuretic peptide, vascular endothelial growth factor, endothelin-1, and nitric oxide synthase in chronic mountain sickness. Am J Physiol Heart Circ Physiol. 300:H1427–1433. 2011. View Article : Google Scholar : PubMed/NCBI