Investigation of toxicological effects of Shuanghuanglian injection in Beagle dogs by metabonomic and traditional approaches.
In this study, clinical biochemistry, hematology, histopathology and (1)H nuclear magnetic resonance spectroscopy-based metabonomic approaches were applied to investigate the toxicological effects of Shuanghuanglian (SHL) injection after intravenous administration (dosed at 4, 12 and 36 mL stock/kg) in Beagle dogs for 30 d. Decreases in red blood cells, hemoglobin, mean cell volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were observed in the high-dose group. Elevated reticulocytes, total bilirubin and direct bilirubin were also observed in this group. Moreover, significant hemosiderosis and Prussian blue positivity were detected in the liver, spleen and kidney from high-dose group animals, and transmission electron microscopy examination revealed an appreciable number of acanthrocytes in the liver. These results collectively indicate that SHL injection has the potential to cause hemolytic anemia. Metabonomic analysis showed increases in serum lactate, choline and phosphocholine but a decrease in taurine in treated groups and these findings may underlie the toxicological mechanism of SHL injection. In summary, SHL injection shows hemolytic effects in Beagle dogs; moreover, serum choline and phosphocholine as well as lactate and taurine may be the biomarkers for hemolytic anemia induced by SHL injection.
Yan
Guangyan
G
National Chengdu Center for Safety Evaluation of Drugs, West China Hospital of Sichuan University, Chengdu 610041, China.
Zhao
Yinglan
Y
Deng
Pengchi
P
Lv
Lei
L
Wang
Yanli
Y
Bu
Qian
Q
Liu
Bin
B
Hu
Chunyan
C
Zhuo
Yanqiang
Y
Yang
Xunning
X
Wang
Li
L
Cen
Xiaobo
X
D000743:Anemia, Hemolytic / Q000139:chemically induced* / Q000175:diagnosis / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002794:Choline / Q000097:blood; D004285:Dogs; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000633:toxicity*; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D055432:Metabolomics; D019906:Nuclear Magnetic Resonance, Biomolecular; D009929:Organ Size / Q000187:drug effects; D010767:Phosphorylcholine / Q000097:blood; D044967:Serum / Q000737:chemistry / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D013654:Taurine / Q000097:blood
D015415:Biomarkers; D004365:Drugs, Chinese Herbal; C516400:shuang-huang-lian; D010767:Phosphorylcholine; D013654:Taurine; D019344:Lactic Acid; D002794:Choline