Diluted Isoflurane as a Suitable Alternative for Diethyl ether for Rat Anaesthesia in Regular Toxicology Studies

Abstract

ABSTRACT. Despite its explosive properties and toxicity to both animals and humans, diethyl ether is an agent long used in Japan in the anaesthesia jar method of rat anaesthetises. However, in response to a recent report from the Science Council of Japan condemning diethyl ether as acceptable practice, we searched for an alternative rat anaesthesia method that provided data continuous with pre-existing regular toxicology studies already conducted under diethyl ether anaesthesia. For this, we examined two candidates; 30% isoflurane diluted with propylene glycol and pentobarbitone. Whereas isoflurane is considered to be one of the representatives of modern volatile anaesthetics, the method of propylene glycol-diluted 30% isoflurane used in this study was our modification of a recently reported method revealed to have several advantages as an inhalation anaesthesia. Intraperitoneal pentobarbitone has long been accepted as a humane method in laboratory animal anaesthesiology. These 2 modalities were scrutinized in terms of consistency of haematology and blood chemistry with previous results using ether. We found that pentobarbitone required a much longer induction time than diethyl ether, which is suspected to be the cause of fluctuations in several haematological and blood chemical results. Conversely, only calcium ion concentration showed a slight difference from traditional results in the case of 30% isoflurane. Additionally, serum prolactin and corticosterone levels indicated that 30% isoflurane induced less stress than ether, confirming that 30% isoflurane can both provide results consistent with diethyl ether, while at the same time remove its disadvantages. As such 30% isoflurane appears to be a strong alternative anaesthetic agent for future regular toxicology studies in Japan.

New neurons restore structural and behavioral abnormalities in a rat model of PTSD

“…Similarly, small changes in the protocols for inducing stress may alter the duration of its behavioral effects, as stronger stressors may have longer‐lasting results. One difference between the stress protocol used in the current study and in most previous SPS studies is the replacement of diethyl ether with isoflurane, a less dangerous but less stressful anesthetic (Flecknell, ; Nagate et al, ). Another study, which also used ether, found no effect of SPS on anxiety‐like behavior after 24 days, suggesting a relatively rapid recovery, but because this study did not include a shorter time point it is unclear whether behavior resolved or was unaffected by their paradigm (Wu et al, ).…”

Osteopontin Deficiency Suppresses Intestinal Tumor Development in Apc-Deficient Min Mice

“…The experiments were performed according to the “Guidelines for Animal Experiments of the National Cancer Center” and were approved by the Institutional Ethics Review Committee for Animal Experimentation of the National Cancer Center (permission code: T07-012, approval date: 1 April 2007). Diluted isoflurane [82] was used to anaesthetize the animals.…”

Isoflurane is a suitable alternative to ether for anesthetizing rats prior to euthanasia for gene expression analysis

“…The differences in the values were in the range of what could be expected occasionally in normal rats (from the reference data of 11weeks rat in supplier's home page). Nagate et al (2007) reported no statistically significant differences among ether, isoflurane, and pentobarbital in terms of the hematological parameters of anaesthetized rats. Their data could be compare with our data because strains, ages, and suppliers of the rats in their experiments were the same of us, though there were some differences in the anesthetized methods; isoflurane were used in exclusive apparatuses or glass jars and pentobarbital was injected intraperitoneally at 45 or 50 mg/kg body weight respectively.…”