Effects of adriamycin and candesartan on the collagen and elastin of the aorta in rats
0
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Introduction: It has been reported that the chemotherapeutic agent, adriamycin, not only has an effect on the myocardium but also on the arteries. The aim of this study is to elucidate effects of adriamycin and an angiotensin receptor blocker, candesartan, on collagen and elastin of the aorta in rats. Methods: Twenty four male 8-week-old Wistar-Kyoto rats were divided into four groups: control (C) group, adriamycin-treated (AD) group, candesartan-treated (CA) group, and adriamycin- and candesartan-treated (AD + CA) group. Adriamycin of 2.5 mg/kg/wk was administered intraperitoneally one time per week for 6 weeks, and candesartan of 10 mg/kg/day was administered orally everyday for 6 weeks. After 6 weeks, the rats were sacrificed and the aortas were harvested. Hematoxylin-eosin staining, Verhoff’s elastic, and Goldner’s trichrome staining were performed for histopathologic analyses. Tunica media thickness, collagen, and elastic area fractions were measured quantitatively with a computerized digital image analyzer. Results: Tunica media thickness in the CA and AD + CA groups was significantly lesser than that in the C and AD groups, respectively. The AD and AD + CA groups had a tendency of lower elastin area fraction than the C and CA groups, respectively. Collagen area fraction in the AD + CA group was significantly lower than that in the AD group. There were no significant differences of collagen/elastin ratio between groups. Conclusions: These findings suggest that adriamycin has a tendency of decreasing the quantity of elastin fibers and candesartan cannot mitigate the effects of adriamycin on elastin fibers.
Abstract
Introduction: It has been reported that the chemotherapeutic agent, adriamycin, not only has an effect on the myocardium but also on the arteries. The aim of this study is to elucidate effects of adriamycin and an angiotensin receptor blocker, candesartan, on collagen and elastin of the aorta in rats. Methods: Twenty four male 8-week-old Wistar-Kyoto rats were divided into four groups: control (C) group, adriamycin-treated (AD) group, candesartan-treated (CA) group, and adriamycin- and candesartan-treated (AD + CA) group. Adriamycin of 2.5 mg/kg/wk was administered intraperitoneally one time per week for 6 weeks, and candesartan of 10 mg/kg/day was administered orally everyday for 6 weeks. After 6 weeks, the rats were sacrificed and the aortas were harvested. Hematoxylin-eosin staining, Verhoff’s elastic, and Goldner’s trichrome staining were performed for histopathologic analyses. Tunica media thickness, collagen, and elastic area fractions were measured quantitatively with a computerized digital image analyzer. Results: Tunica media thickness in the CA and AD + CA groups was significantly lesser than that in the C and AD groups, respectively. The AD and AD + CA groups had a tendency of lower elastin area fraction than the C and CA groups, respectively. Collagen area fraction in the AD + CA group was significantly lower than that in the AD group. There were no significant differences of collagen/elastin ratio between groups. Conclusions: These findings suggest that adriamycin has a tendency of decreasing the quantity of elastin fibers and candesartan cannot mitigate the effects of adriamycin on elastin fibers.
참고문헌 (24)
- Weiss RB, "The anthracyclines: will we ever find a better doxorubicin?", Semin Oncol, 19, pp.670~686 (1992)
- Chatterjee K, "Doxorubicin cardiomyopathy", Cardiology, 115, pp.155~162 (2010)
- Murata T, "Chronic vascular toxicity of doxorubicin in an organ-cultured artery", Br J Pharmacol, 132, pp.1365~1373 (2001)
- Murata T, "Chronic effect of doxorubicin on vascular endothelium assessed by organ culture study", Life Sci, 69, pp.2685~2695 (2001)
- Wu S, "Adriamycin-induced cardiomyocyte and endothelial cell apoptosis:in vitro and in vivo studies", J Mol Cell Cardiol, 34, pp.1595~1607 (2002)
- Jugdutt BI, "Pleiotropic effects of cardiac drugs on healing post-MI: the good, bad, and ugly", Heart Fail Rev, 13, pp.439~452 (2008)
- Uhm JS, "Comparison of adriamycin-induced cardiomyopathy in normotensive rats and spontaneously hypertensive rats", Korean Hypertension J, 12, pp.23~30 (2006)
- Konietschke F, "Rank-based multiple test procedures and simultaneous confidence intervals", Electron J Stat, 6, pp.738~759 (2012)
- Wagenseil JE, "Elastin in large artery stiffness and hypertension", J Cardiovasc Transl Res, 5, pp.264~273 (2012)
- De Wildt DJ, "Cardiovascular effects of doxorubicin-induced toxicity in the intact Lou", M Wsl rat and in isolated heart preparations, 1985, pp.235, 234~240
- Kim TS, "From hypertension to heart failure", Korean Hypertension J, 15, pp.1~11 (2009)
- Pitt B, "The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators", N Engl J Med, 341, pp.709~717 (1999)
- Lopez B, "Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure", J Am Coll Cardiol, 43, pp.2028~2035 (2004)
- Yamaç D, "Ultrastructural damage in vascular endothelium in rats treated with paclitaxel and doxorubicin", Ultrastruct Pathol, 30, pp.103~110 (2006)
- Nicolson GL, "Effects of chemotherapeutic drugs on platelet and metastatic tumor cell-endothelial cell interactions as a model for assessing vascular endothelial integrity", Cancer Res, 45, pp.331~336 (1985)
- Ulu N, "Vascular dysfunction in adriamycin nephrosis: different effects of adriamycin exposure and nephrosis", Nephrol Dial Transplant, 23, pp.1854~1860 (2008)
- Den Hartog GJ, "Lack of inhibition of endothelial nitric oxide synthase in the isolated rat aorta by doxorubicin", Toxicol In Vitro, 17, pp.165~167 (2003)
- Vasquez-Vivar J, "Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin", Biochemistry, 36, pp.11293~11297 (1997)
- Keltai K, "Doxorubicin selectively suppresses mRNA expression and production of endothelin-1in endothelial cells", Vascul Pharmac, 53, pp.209~214 (2010)
- Maney SK, "Effect of apoptosis-inducing antitumor agents on endocardial endothelial cells", Cardiovasc Toxicol, 11, pp.253~262 (2011)
- Swystun LL, "Chemotherapeutic agents doxorubicin and epirubicin induce a procoagulant phenotype on endothelial cells and blood monocytes", J Thromb Haemost, 7, pp.619~626 (2009)
- Dalske HF, "Effect of low-dose doxorubicin on calcium content and norepinephrine response in rat aorta", Eur J Cancer Clin Oncol, 24, pp.979~983 (1988)
- Jeansson M, "Haraldsson B: Adriamycin alters glomerular endothelium to induce proteinuria", J Am Soc Nephrol, 20, pp.114~122 (2009)
- Julius S, "Feasibility of treating prehypertension with an angiotensin-receptor blocker", N Engl J Med, 354, pp.1685~1697 (2006)