ABSTRACT
The effects of long-term chronic ketamine treatment on the intestine and the liver were studied in the ICR mice which had daily intraperitoneal injection of ketamine at 30 mg/kg per day for 7 months. The intestine showed no significant pathology after treatment but had a decrease of the positive sites of proliferative cell nuclear antigen in the mucosae of the intestines after ketamine and ketamine plus alcohol (added in the last month) treatment. No significant apoptosis (via TUNEL) nor necrosis (via lactic acid dehydrogenase) was detected in the intestines of all control and ketamine-treated groups, with the exception of an increase of lactic acid dehydrogenase in the mucosae of the intestines of the ketamine plus alcohol group. In the liver, loss of glycogen was observed in animals after ketamine and ketamine plus alcohol treatment, in addition to the pathology reported in a previous work. The decrease in quantity of glycogen in the liver reflected either a failure of glycogen synthesis from glucose or an increase of glycogenolysis in the liver.
Subject(s)
Alcohols/administration & dosage , Alcohols/adverse effects , Intestines/pathology , Ketamine/administration & dosage , Ketamine/adverse effects , Liver/pathology , Animals , Apoptosis , Glycogen/analysis , Injections, Intraperitoneal , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Intestines/drug effects , L-Lactate Dehydrogenase/analysis , Liver/drug effects , Mice , Mice, Inbred ICRABSTRACT
Ketamine used as an injectable anesthetic in human and animal medicine is also a recreational drug used primarily by young adults often at all night dance parties in nightclubs. The percentage of ketamine users has grown very fast in the last 5 years worldwide. However, this leads to the serious question of the long-term adverse effects of ketamine on our nervous system, particularly the brain, because ketamine as an NMDA antagonist could cause neurons to commit apoptosis. Our study therefore aimed to find out the chronic effect of ketamine on neuron using prolonged incubation (48 h) of neuronal cells with ketamine in culture. Our results showed that differentiated neuronal cells were prone to the toxicity of ketamine but probably less susceptible than undifferentiated neuronal cells and fibroblasts. This suggested that the ketamine abuse would be harmful to many other organs as well as the brain. Our results also confirmed that the toxicity of ketamine is related to apoptosis via the Bax/Bcl-2 ratio pathway and caspase-3 in the differentiated neuronal cells. Therefore, long-term ketamine treated cell or animal models should be sought to study this multiorgan effects of ketamine.
