title: Toxicity of Evodiae fructus on rat liver mitochondria: the role of oxidative stress and mitochondrial permeability transition.
abstract: Evodiae fructus (EF) has been used in China for thousands of years as an analgesic, antiemetic, anti-inflammatory and antidiarrheal drug. EF is a toxic drug and causes hepatotoxicity in humans. Although recent chronic toxicity studies performed on aqueous extract of EF has revealed that it can produce obvious cumulative hepatotoxicity, the mechanism behind this toxicity is still uncertain. In the present study, we investigated the influence of EF on oxidative stress, mitochondrial permeability transition, adenosine triphosphate (ATP), and cytochrome C release of hepatic mitochondria. Rats were divided into four groups and fed distilled water, 6, 12, 24 g/kg of aqueous extract of EF daily for 15 days. Evodiamine, rutaecarpine and evodine were quantified in the aqueous extract by high performance liquid chromatography with ultraviolet detection (HPLC/UV). The results showed that aqueous extract of EF could significantly (p < 0.05) decrease MnSOD levels to 56.50%, 46.77% and 19.67% of control group, GSH level was decreased to 74.24%, 53.97% and 47.91% of control group and MDA level was increased to 131.55%, 134.34% and 150.81% of control group in the 6, 12 and 24 g/kg groups, respectively; extract also induced mitochondria swelling, vacuolation, MPT pore opening and a significant decrease (p < 0.05) in mitochondrial potential, while ATP levels were significant decreased (p < 0.05) to 65.24%, 38.08% and 34.59% of control group in the 6, 12 and 24 g/kg groups, respectively, resulting in ATP depletion and CytC release, finally trigger cell death signaling, which are the partial hepatotoxicity mechanisms of EF.
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. cqywho@163.com.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. weijingjingfhl@163.com.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wei
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. athenaty@gzucm.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. m18825141524@163.com.
authors.forename: Si
authors.initials: S
authors.lastname: Shi
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. zy970838172@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. weirenrong@126.com.
authors.forename: Renrong
authors.initials: R
authors.lastname: Wei
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. zy970838172@163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. liwr@gzucm.edu.cn.
authors.forename: Weirong
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. wangqi@gzucm.edu.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D045304:Cytochromes c / Q000378:metabolism; D032086:Evodia / Q000737:chemistry*; D005663:Furans; D005978:Glutathione / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings; D026121:Indole Alkaloids / Q000737:chemistry; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity*; D011799:Quinazolines / Q000737:chemistry; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D052999:Quinazolinones
chemical_list: D000255:Adenosine Triphosphate; D045304:Cytochromes c; D005663:Furans; D005978:Glutathione; D006576:Heterocyclic Compounds, 4 or More Rings; D026121:Indole Alkaloids; D008315:Malondialdehyde; D010936:Plant Extracts; D011799:Quinazolines; D013482:Superoxide Dismutase; C473746:evodine; C028632:rutecarpine; D052999:Quinazolinones; C049639:evodiamine