Gallic acid exhibits risks of inducing muscular hemorrhagic liposis and cerebral hemorrhage--its action mechanism and preventive strategy.
Gallic acid (3,4,5-trihydroxybenzoic acid) (GA) occurs in many plants. The adverse effects of GA are seldom cited. GA (6-14 μM) provoked the hemorrhagic liposis of the cervical muscles and intracranial hemorrhage. The cause of these pathological events and the method for prevention are still lacking. Using the chicken embryo model and some selected nutraceutics such as folate, glutathione (GSH), N-acetylcysteine, and vitamin E (Vit E), we carried out this study. Results revealed that the action mechanism of GA involved (i) inducing hypoxia with upregulated gene hif-1α and downregulated ratio vegf-r2/vegf-a, leading to dys-vascularization and myopathy; (ii) impairing cytochrome c oxidase; (iii) stimulating creatine kinase and lactate dehydrogenase release; (iv) eliciting carnitine accumulation and liposis via downregulating gene CPT1; (v) suppressing superoxide dismutase and stimulating NO, H2O2, and malondialdehyde; and (vi) depleting erythrocytic and tissue GSH, resulting in hemorrhage. When both Vit E and GSH were applied to the day 1 chicks, a better alleviation effect was revealed. Conclusively, GA potentially exhibits adverse effect by eliciting hemorrhagic liposis of cervical muscles and cerebral hemorrhage. Supplementation with GSH, Vit E, and N-acetylcysteine is able to ameliorate these adverse effects, warranting the importance of restricting the clinical phytotherapeutic doses of GA and related compounds.
Graduate Institute of Biotechnology, Changhua University of Education, 1 Jin-De Road, Changhua, 50007, Taiwan.
Chiu-Lan
CL
Hsieh
Chien-Hong
CH
Lin
Hui-Er
HE
Wang
Chiung-Chi
CC
Peng
Robert Y
RY
Peng
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002543:Cerebral Hemorrhage / Q000139:chemically induced*; D002642:Chick Embryo; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000139:chemically induced; D005707:Gallic Acid / Q000009:adverse effects* / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009334:Neck Muscles / Q000187:drug effects* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D014810:Vitamin E; D005707:Gallic Acid; D040301:Vascular Endothelial Growth Factor Receptor-2; D005978:Glutathione; D000111:Acetylcysteine
gallic acid; genes CPT1 and vegf; glutathione; hemorrhagic liposis; vitamin E