Vitamin K1 (VK1) has been widely used as a coumarin antagonist and for the treatment of hemorrhagic disease in veterinary practice. However, the potential mechanism of adverse reaction after VK1 injection has been not fully elucidated. In this study, two cases of anaphylactic reactions after subcutaneous VK1 injection were presented, and then an experimental study was performed to further characterize the anaphylactic reactions. Two dogs developed anaphylactic reactions after subcutaneous VK1 injections and were promptly treated with antihistamines and glucocorticoids, after which abnormal signs related to anaphylaxis disappeared. Subsequently, a study was undertaken to ascertain the nature of the adverse reactions to subcutaneous VK1 injection. Six healthy laboratory beagle dogs received subcutaneous VK1 administrations once daily for eight days. They were monitored for clinical signs after each injection, and blood samples were collected for the measurement of plasma histamine and immunoglobulin E concentrations using enzyme-linked immunosorbent assay. All six dogs showed mild angioedema after the VK1 injections. The dogs also displayed clinical signs including sneezing, coughing, skin reddening, excess salivation, pawing the ground, and somnolence on days 4, 6, and 8. Plasma histamine and immunoglobulin E concentrations were significantly increased by the repeated injections. In summary, this study describes anaphylactic reactions resulting from subcutaneous VK1 administration in dogs. Clinicians should be aware that the repeated subcutaneous injection of VK1 can trigger an anaphylactic reaction in dogs.

Aralia elata, Chaenomeles sinensis fruit, and Glycyrrhizae radix have been widely used as oriental medicinal plants in Korea, China and Japan and found to possess anti-oxidative and anti-inflammatory activities. The current study was conducted to investigate the neuroprotective effect of an ethanol extract of a mixture of A. elata, C. sinensis fruit, and Glycyrrhizae radix (ACG) against ischemia-induced brain injury in rats and excitotoxic and oxidative neuronal death in primarily cultured rat cortical neurons. Transient focal cerebral ischemia was induced by 2 h middle cerebral artery occlusion followed by 24 h reperfusion (MCAO/R) in rats. Oral administration of ACG (10, 25, and 50 mg/kg) 30 min before MCAO, after 1 h of MCAO, and after 1 h of reperfusion reduced MCAO/R-induced brain infarct and edema formation. ACG also inhibited development of behavioral disabilities in MCAO/R-treated rats. Exposure of cultured cortical neurons to 500 μM glutamate for 12 h resulted in neuronal cell death. ACG (1, 10, and 50 μg/mL) inhibited glutamate-induced neuronal death. Furthermore, ACG inhibited 100 μM hydrogen peroxide (H2O2)- and hypoxia-induced neuronal death. These results suggest that the neuroprotective effect of ACG against ischemia-induced brain damage might be associated with its anti-excitotoxic and anti-oxidative activity and that ACG may have a therapeutic role for prevention of neurodegeneration in stroke.