Browse > Article

Protection by Paeonol on Cytotoxicity of Cultured Rat Hepatocytes Exposed to Br-A23187  

Bae, Ki-Hwan (Department of Pharmacognosy, College of Pharmacy, Chungnam National University)
Kim, Young-Ho (Department of Pharmacognosy, College of Pharmacy, Chungnam National University)
Oh, Ki-Wan (Department of Pharmacology, College of Pharmacy, Chungbuk National University)
Publication Information
Biomolecules & Therapeutics / v.11, no.3, 2003 , pp. 174-177 More about this Journal
Abstract
The present experiment was performed to investigate the protective effects of paeonol isolated from Moutan Cortex Radicis on primary cultured rat hepatocytes exposed to Br-A23187 ($Ca^{2+}$ ionophore). Br-A23187 is frequently used as a model of cell killing as inducing both necrotic and apoptotic cell death. Hepatocytes were isolated by collagenase perfusion from livers of fasted male Sprague Dawley rats and cultured overnight. Cell viability was determined by propidium iodide using fluorocytometry in Krebs-Ringer-HEPES buffer at pH 7.4. In addition, intracellular calcium was measured by excitation at 340 and 380 nm and emission at 505 nm using a luminescence spectrophotometer. Paeonol (20-100 ${\mu}M$) inhibited cell killing induced by 10 ${\mu}M$ Br-A23187, in a dose-dependent manner. Paeonol also reduced increased intracellular calcium level when hepatocytes were exposed to Br-A23187. Therefore, the present results suggest that paeonol protects the hepatocytotoxicity induced by Br-A23187, via inhibiting the influx of calcium into into rat hepatocytes.
Keywords
Hepatocytes; Paeonol; Br-A23187; Intracellular [$Ca^{2+}$]; Cytotoxicity;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Fu, Q. L. (1992). Experimental study on yiqi-huoxue therapy of liver fibrosis. Zhongguo Zhong Xi Yi Jie He Za Zhi, 12, 228229
2 Gores, G. J., Nieminen, A-L., Fleishman, K. E., Dawson, T. L., Herman, B. and Lemasters, J. J. (1988). Extracellular acidosis delays onset of cell death in ATP depleted hepatocytes. Am. J. Physiol., 255, C315-322   DOI
3 Harata, M., Yamashita, A and Aburada, M. (1972). Pharmacological studies on the root bark of Paeonia Moutan, II. Antiinflammatory effects, preventive effects on stress-induced gastric erosion, inhibitory effects on gastric juice secretion and other effects of paeonol. Yakugaku Zasshi, 92, 750-756   DOI
4 Kawanishi, T., Nieminen, A-L., Herman, B. and Lemansters, J. J. (1991). Suppression of Ca2+ oscillation in cultured hepatocytes by chemical hypoxia. J. BioI. Chern., 266, 20062-20069
5 McConkey, D. J. and Orrenius, S. (1996). The role of calcium in the regulation of apoptosis. J. Leuk. Biol., 59, 775-783   DOI
6 Nieminen, A-L., Gores, G. J., Bond, J. M., Imberti, B., Herman, B. and Leamsters, 1. 1. (1992). A novel cytotoxicity screening assay using a multi well t1uorescence scanner. Toxicol. Appl. Pharmacol., 115, 147-155   DOI   ScienceOn
7 Qi, X. G. (1991). Protective mechanism of Salvia miltiorrhiza and Paeonia lactiflora for experimental liver damage. Zhongguo Zhong Xi Yi Jie He Za Zhi, 11, 102-104
8 Qian, T., Herman, B. and Lemasters, J. J. (1999). The mitochondrial permeability transition mediates both necrotic and apoptotic death of hepatocytes exposed to Br-A23187, Toxicol. Appl. Pharmacol., 154, 117-125   DOI   ScienceOn
9 Shi, L., Fan, P. S., Fang, J. X. and Han, Z. X. (1988). Inhibitory effects of paeonol on experimental atherosclerosis and platelet aggregation of rabbit. Acta Pharmacologica Sinica, 9, 555558
10 Yoshikawa, M., Uchida, E., Kawaguchi, A, Kitagawa, I. and Yamahara, J. (1992). Galloryl-oxypaeoniflorin, suffruticosides A, B, C, and D, antioxidative glycosides, and suffruticosides E, a paeonol glycosides, from Chinese Moutan Cortex. Chem. Pharm. Bull., 40, 2248-2250   DOI   ScienceOn
11 Trump, B. F. and Berezesky, I. K. (1995). Calcium-mrdiated cell injury and cell death. FASEB J., 9, 219-228   DOI
12 Goto, H., Shimada, Y, Akechi, Y, Kohta, K., Hattori, M. and Terasawa, K. (1996). Endothelium-dependent vasodilatator effects of extract prepared from the roots of Paeonia lactiflora on isolated rat aorta. Planta Med., 62, 436-439.   DOI   ScienceOn
13 Grynkiewicz, G., Poenie, M. and Tsien, R. Y (1985). A new generation of $Ca^{z+}$ indicators with greatly improved fluorescence properties. J. BioI. Chem., 260, 3440-3450
14 Harada, M. and Yamashita, A (1969). Pharmacological studies on the root of bark of Paeonia moutan. r. Central effects of paeonol. Yakugaku Zasshi, 89, 1205-1211   DOI
15 Shibutani, S., Nagasawa, T., Oura, H. Nonata, G., and Nishioka 1. (1981). Effects of extract from Paeoniae Radix on urea-nitrogen concentration in rat serum. Chem. Pharm. Bull., 29, 87487
16 Tang, J. R. and Shi, L. (1991). The inhibitory effects of sodium paeonol sulfate on calium influx in the cultured neonatal rat heart cells during calcium paradox, Acta Pharmaceutica Shinica, 26(3), 161-165
17 Wyllie, A I-I., Morris, R. G., Smith, A L., and Dunlop, D. (1984). Chromatin cleavage in apoptosis: Association with condensed chromatin morphology and dependence on macromolecular synthesis. J. Pathol. 142, 67-77   DOI