title: Effects of emodin treatment on mitochondrial ATP generation capacity and antioxidant components as well as susceptibility to ischemia-reperfusion injury in rat hearts: single versus multiple doses and gender difference.
abstract: Effects of emodin (EMD) treatment on mitochondrial ATP generation capacity and antioxidant components as well as susceptibility to ischemia-reperfusion (I-R) injury were examined in male and female rat hearts. Isolated-perfused hearts prepared from female rats were less susceptible to I-R injury than those of male rats. I-R caused significant decreases in ATP generation capacity and reduced glutathione (GSH) and alpha-tocopherol (alpha-TOC) levels as well as glutathione reductase, Se-glutathione peroxidase and Mn-superoxide dismutase (SOD) activities. The lower susceptibility of female hearts to myocardial I-R injury was associated with higher levels of GSH and alpha-TOC as well as activity of SOD than those of male hearts. EMD treatment at 3 daily doses (0.6 or 1.2 mmol/kg) could enhance myocardial mitochondrial ATP generation capacity and antioxidant components in both male and female rat hearts, but it only significantly protected against I-R injury in female hearts. Treatment with a single dose of EMD invariably enhanced mitochondrial antioxidant components and protected against I-R injury in both male and female hearts. The gender-dependent effect of EMD treatment at multiple doses may be related to the differential antioxidant response in the myocardium and/or induction of drug metabolizing enzymes in the liver.
authors.affiliation: Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Du
authors.forename: Kam Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004642:Emodin / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000378:metabolism; D024502:alpha-Tocopherol / Q000378:metabolism
chemical_list: D000975:Antioxidants; D000255:Adenosine Triphosphate; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione; D024502:alpha-Tocopherol; D004642:Emodin