Abstract
Isolated Langendorff-perfused rat hearts were subjected to a fixed period of ischemia followed by increasing periods of reperfusion for investigating the changes in the extent of ischemia-reperfusion (IR) injury and tissue levels of non-enzymatic antioxidants. Effects of schisandrin B (Sch B) and (±) α-lipoic acid (LA) pretreatment were also examined. A 40-min of ischemia (40-I) followed by 20- or 40-min of reperfusion (20-R or 40-R) caused sustainable tissue damage in isolated hearts, as indicated by the increased extent of lactate dehydrogenase (LDH) leakage and impaired contractile force. The myocardial IR injury was associated with a marked decrease in tissue ascorbic acid (VC) level. However, myocardial reduced glutathione (GSH) and α-tocopherol (VE) levels remained relatively unchanged except under a more severe IR condition (40-I, 40-R). Pretreating rats with Sch B or LA at a daily dose of 1.2 mmol/kg for 3 days protected against IR injury in isolated hearts to varying degrees. While only Sch B pretreatment could improve the recovery of contractile force, LA pretreatment produced a better inhibitory effect on LDH leakage. The protection against IR injury was associated with significant increases in myocardial VE and VC levels in both Sch B and LA pretreated hearts. The ensemble of results suggests that the cardioprotection afforded by Sch B or LA pretreatment may at least in part be attributed to the modulation on the interplay among non-enzymatic antioxidants under oxidative stress induced by IR.
Similar content being viewed by others
References
Chen SY, Li F: Tonics and astringents. In: F. Diebschlag (ed). Clincal Guide to Chinese Herbs and Formulae. Churchill Livingstone, London, 1993, p 75
Ko KM, Yick PK, Poon MKT, Che CT: Schisandra chinensis-derived antioxidant activities in 'sheng Mai San', a compound formulation, in vivo and in vitro. Phytother Res 9: 203–206, 1995
Li X, Zhao B, Liu G, Xin W: Scavenging effects on active oxygen radicals by schizandrins with different structures and configurations. Free Rad Biol Med 9: 99–104, 1990
Mak DHF, Ip SP, Li PC, Poon MKT, Ko KM: Effects of schisandrin B and a-tocopherol on lipid peroxide, in vitro and in vivo. Mol Cell Biochem 165: 161–165, 1996
Ip SP, Poon MKT, Wu SS, Che CT, Ng KH, Kong YC, Ko KM: Effect of schisandrin B on hepatic glutathione antioxidant system in mice: Protection against carbon tetrachloride toxicity. Planta Med 61: 398–401, 1995
Yim TK, Ko KM: Schisandrin B protects against myocardial ischemiareperfusion injury by enhancing myocardial glutathione antioxidant status. Mol Cell Biochem 196: 151–156, 1999
Packer L, Tritschler HJ, Wessel K: Neuroprotection by the metabolic antioxidant a-lipoic acid. Free Rad Biol Med 22: 359–378, 1997
Yim TK, Wu WK, Mak DHF, Ko KM: Myocardial protective effect of an anthraquinone-containing extract of Polygonum multiflorum ex vivo. Planta Med 64: 587–682, 1998
Li PC, Mak DHF, Poon MKT, Ip SP, Ko KM: Myocardial protective effect of Sheng Mai San (SMS) and a lignan-enriched extract of Fructus Schisandrae, in vivo and ex vivo. Phytomedicine 3: 217–321, 1996
Reed DJ, Babson JR, Beatty PW, Brodie AE, Ellis WW, Potter DW: High-performance liquid chromatography analysis of nanomole levels of glutathione, glutathione disulfide, and related thiols and disulfides. Anal Biochem 106: 55–62, 1980
Ip SP, Ko KM: The crucial antioxidant action of schisandrin B in protecting against carbon tetrachloride hepatotoxicity in mice: A comparative study with butylated hydroxytoluene. Biochem Pharmacol 52: 1687–1693, 1996
Liau LS, Lee BL, New AL, Ong CN: Determination of plasma ascorbic acid by high-performance liquid chromatography with ultraviolet and electrochemical detection. J Chromatogr 612: 63–70, 1993
Sadrzadeh SMH, Nanji AA, Meydani M: Effect of chronic ethanol feeding on plasma and liver a-and g-tocopherol levels in normal and vitamin E-deficient rats: Relationship to lipid peroxidation. Biochem Pharmacol 47: 2005–2010, 1994
Takemura G, Onodera T, Ashraf M: Hydroxyl radical production during early reperfusion after different periods of ischemia in rat hearts and its effect on myocardial function. Am J Cardiovasc Pathol 4: 165–174, 1992
Kaul N, Siveski-Iliskovic N, Hill M, Slezak J, Singal PK: Free radicals and the heart. J Pharmacol Toxicol Meth 30: 55–67, 1993
Baker JE, Felix CC, Olinger GN, Kalyanaraman B: Myocardial ischemia and reperfusion: Direct evidence for free radical generation by electron spin resonance spectroscopy. Proc Natl Acad Sci USA 85: 2786–2789, 1988
Maupoil V, Rochette L: Evaluation of free radical and lipid peroxide formation during global ischemia and reperfusion in isolated perfused rat heart. Cardiovasc Drugs Ther 2: 615–612, 1988
Esterbauer H, Schaur RJ, Zollner H: Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Rad Biol Med 11: 81–128, 1991
Ambrosio G, Flaherty JT, Duilio C, Tritto I, Santoro G, Elia PP, Condorelli M, Chiariello M: Oxygen radicals generated at reflow in-147 duce peroxidation of membrane lipids in reperfused hearts. J Clin Invest 87: 2056–2066, 1991
Manciet LH, Copeland JG: Lipid peroxidation results in compromised functional recovery of isolated rabbit hearts after low-pressure, hypothermic, perfused preservation for 24 h. J Thorac Cardiovasc Surg 103: 532–540, 1992
Nagy A, Sellei P, Valen G. Sjoquist PO, Vaage J: Effects of a lowmolecular weight antioxidant on cardiac injury induced by hydrogen peroxide. Free Rad Biol Med 20: 567–572, 1996
Kaneko M, Beamish RE, Dhalla NS: Reduction of calcium channel antagonist binding sites by oxygen free radicals in rat heart. J Mol Cell Cardiol 21: 935–943, 1989
Wells WW, Xu DP: Dehydroascorbate reduction. J Bioenerg Biomembr 26: 369–377, 1994
Haramaki N, Stewart DB, Aggarwal S, Ikeda H, Reznick AZ, Packer L: Networking antioxidants in the isolated rat heart are selectively depleted by ischemia-reperfusion. Free Rad Biol Med 25: 329–339, 1998
Galaris D, Cadenas E, Hochstein P: Glutathione-dependent reduction of peroxides during ferryl-and met-myoglobin interconversion: A potential protective mechanism in muscle. Free Rad Biol Med 6: 473–478, 1989
Galaris D, Cadenas E, Hochstein P: Redox cycling of myoglobin and ascorbate: A potential protective mechanism against reperfusion injury in muscle. Arch Biochem Biophys 273: 497–504, 1989
Tritto I, Duilio C, Santoro G., Elia PP, Cirillo P, De Simone C, Chiariello M, Ambrosio G: A short burst of oxygen radicals at reflow induces sustained release of oxidized glutathione from postischemic hearts. Free Rad Biol Med 24: 290–297, 1998
Gate L, Paul J, Nguyen BA, Tew KD, Tapiero H: Oxidative stress induced in pathologies: The role of antioxidants. Biomed Pharmacother 53: 169–180, 1999
Sharma MK, Buettner GR, Spencer KT, Kerber RE: Ascorbyl free radical as a real-time marker of free radical generation in briefly ischemic and reperfused hearts. Circ Res 74: 650–658, 1994
Rigobello MP, Bindoli A: Effect of pyruvate on rat heart thiol status during ischemia and hypoxia followed by reperfusion. Mol Cell Biochem 122: 93–100, 1993
Venditti P, Masullo P, Di Meo S, Agnisola C: Protection against ischemia-reperfusion induced oxidative stress by vitamin E treatment. Arch Physiol Biochem 107: 27–34, 1999
Packer JE, Slater TF, Willson RL: Direct observation of a free radical interaction between vitamin E and vitamin C. Nature 278: 737–738, 1979
Leedle RA, Aust SD: The effect of glutathione on the vitamin E requirement for inhibition of liver microsomal lipid peroxidation. Lipids 25: 241–245, 1990
Chan AC, Tran K, Raynor T, Ganz PR, Chow CK: Regeneration of vitamin E in human platelets. J Biol Chem 266: 17290–17295, 1991
Wolz P. Krieglstein J: Neuroprotective effects of alpha-lipoic acid and its enantiomers demonstrated in rodent models of focal cerebral ischemia. Neuropharmacol 35: 369–375, 1996
Schonheit K, Gille L, Nohl H: Effect of alpha-lipoic acid and dihydrolipoic acid on ischemia/reperfusion injury of the heart and heart mitochondria. Biochim Biophys Acta 1271: 335–342, 1995
Wells WW, Xu DP, Yang YF, Rocque PA: Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity. J Biol Chem 265: 15361–15364, 1990
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ko, KM., Yiu, HY. Schisandrin B modulates the ischemia-reperfusion induced changes in non-enzymatic antioxidant levels in isolated-perfused rat hearts. Mol Cell Biochem 220, 141–147 (2001). https://doi.org/10.1023/A:1010979404447
Issue Date:
DOI: https://doi.org/10.1023/A:1010979404447