Abstract
2,3,5,6-Tetramethylpyrazine (TMP) is well known as a true calcium antagonist. The aim of this study was to investigate the hepatoprotective and therapeutic effects of TMP on acute econazole-induced liver injury. The hepatological effect of various concentrations of TMP was first assessed by the biochemical assays of SGOT and SGPT and then by hepatohistological microscopic examination. The dose-response relationship of liver injury induced by various doses of econazole was observed simultaneously from serum biochemical assay of SGOT and SGPT, and also from hepatohistological microscopic examination, by determination of the hepatoprotective effects of various concentrations of TMP on SGOT and SGPT elevation induced by a hepatotoxic dose of econazole (300 mg/kg). The inhibitory effect of various concentrations of TMP or vitamin E (positive control, 0.5 mM in vitro, 0.69 mM in vivo) on FeCl2-induced (in vitro) or econazole-induced (in vivo) lipid peroxidation was also investigated. The superoxide scavenging activity of various concentrations of TMP in econazole-damaged rat liver homogenate was assessed by the cytochrome C reduction method. Results showed that the hepatoprotective effect of TMP might be, at least in part, due to its inhibitory ability on membrane lipid peroxidation and free radical formation, or due to its free radical scavenging ability. Improvement of serum transaminases and MDA levels in rat liver homogenate, hepatohistological microscopic examination, and assessment of free radical scavenging activity by the cytochrome C reduction method were used to detect hepatoprotective and therapeutic effects of TMP on acute econazole-induced liver injury.
Abbreviations
TMP:tetramethylpyrazine
MDA:malonic dialdehyde
SGOT:serum aspartate transaminase
SGPT:serum alanine transaminase
Key words
Tetramethylpyrazine - lipid peroxidation - superoxide scavenging - cytochrome C
References
-
1
Pang P K, Shan J J, Chiu K W.
Tetramethylpyrazine, a calcium antagonist.
Planta Medica.
1996;
62
431-5
-
2
Zeng Z, Zhu W, Zhou X, Jin Z, Liu H, Chen X, Pan J, Demura H, Naruse M, Shi Y.
Tetramethylpyrazine, a Chinese drug, blocks coronary vasoconstriction by endothelin-1 and decreases plasma endothelin-1 levels in experimental animals.
Journal of Cardiovascular Pharmacology.
1998;
31
313-6
-
3
Kwan C Y, Gaspar V, Shi A G, Wang Z L, Chen M C, Ohta A, Cragoe E J, Daniel E E.
Vascular effects of tetramethylpyrazine: direct interaction with Smooth muscle alpha-adrenoceptors.
European Journal of Pharmacology.
1991;
198
15-21
-
4
Richelmi P, Baldi C, Manzo L, Berte F, Martino A P, Mirabelli F, Bellomo G.
Erythromycin estolate impairs the mitochondrial and microsomal calcium homeostasis: correlation with hepatotoxicity.
Archive Toxicology, Supplement.
1984;
7
298-302
-
5
Raab W, Hogl F.
The action of antifungal imidazole derivatives on rat liver microsomes.
Mykosen.
1982;
25
431-8
-
6
Lv K, Li H, Ding M.
Analysis of tetramethylpyrazine in Ephedrae herba by gas chromatography-mass spectrometry and high-performance liquid chromatography.
Journal of Chromatography A.
2000;
878
147-52
-
7
Gorska P.
Principles in laboratory animal research for experimental purposes.
Medical Science Monitor.
2000;
6
171-80
-
8
Bergmeyer H U, Scheibe P, Wahlefeld A W.
Optimization of methods for aspartate aminotransferase and alanine aminotransferase.
Clinical Chemistry.
1978;
24
58-73
-
9
Yuda Y, Tanaka J, Hirano F, Igarashi K, Satoh T.
Participation of lipid peroxidation in rat pertussis vaccine pleurisy. III. Thiobarbituric acid (TBA) reactant and lysosomal enzyme.
Chemical Pharmacology Bulletin.
1991;
39
505-6
-
10
Wong S H, Knight J A, Hopfer S A, Zaharia O, Leach C N, Sunderman F W.
Lipoperoxide in plasma as measured by liquid-chromatographic Separation of malondialdehyde-thiobarbituric acid adduct.
Clinical Chemistry.
1987;
33
214-20
-
11
McCord J M, Fridovich I.
The reduction of cytochrome c by milk xanthine oxidase.
Journal of Biological Chemistry.
1968;
243
5753-60
-
12
Suzuki Y, Ishihara M, Segami T, Ito M.
Anti-ulcer ffects of antoxidants, quercetin, alpha-tocopherol, nifedipine and tetracycline in rats.
Japanese Journal of Pharmacology.
1998;
78
435-41
-
13
Feng J, Liu R, Wu G, Tang S.
Effects of tetramethylpyrazine on the release of PGI2 and TXA2 in the hypoxic isolated rat heart.
Molecular Cell Biochemistry.
1997;
167
153-8
-
14
Liao F L, Li B.
Inhibition of shear-induced platelet aggregation by Chinese herbal medicine.
Clinical Hemorheology Microcirculation.
1997;
17
315-8
-
15
Liao M H, Wu C C, Yen M H.
Beneficial effects of tetramethylpyrazine, an active constituent of Chinese herbs, on rats with endotoxemia.
Life Science.
1998;
22
46-54
-
16
Liu S Y, Sylvester D M.
Antiplateletlet structure-activity relationship of tetramethylpyrazine.
Life Science.
1994;
55
1317-26
-
17
Sheu J R, Kan Y C, Huang W C, Ko W C, Yen M H.
Mechanisms involved in the antiplatelet activity of tetramethylpyrazine in human platelets.
Thrombolytic Research.
1997;
88
259-70
-
18
Xue Q F.
Effect of Ligustrazine and Saliva miltiorrhiza on microcirculation in the hamster cheek pouch.
Chung-Hua I Hsueh Tsa Chih (Chin Med J).
1986;
66
334-37, 82
-
19
Xue Q F, Dai S L, Yuan S Y, Zhu L X, Wu Y Q, Wang S S, Li C C, Liu C Y, Wang Z Y.
Effects of Chuanxiongqin (tetramethylpyrazine) on microcirculatory perfusion in hamsters and capillary permeability in rats.
Proceedings of the Chinese Academy of Medical Sciences and the Peking Union Medical College.
1989;
4
224-8
-
20
Heel R C, Brogden R N, Speight T M, Avery G S.
Econazole: a review of its antifungal activity and therapeutic efficacy.
Drugs..
1978;
16
177-201
Song-Chow Lin,Ph. D.
Professor of Pharmacology
Department of Medicine
Taipei Medical University
250, Wu-hsing Street
Taipei
Taiwan, R.O.C.
Phone: +886-2-27361661 EXT.3196(O)
Fax: +886-2-27253536(H)
Email: songchow@tmu.edu.tw
