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

Abstract

Diethyl ether (ether) had been widely used in Japan for anesthesia, despite its explosive properties and toxicity to both humans and animals. We also had used ether as an anesthetic for euthanizing rats for research in the Toxicogenomics Project (TGP). Because the use of ether for these purposes will likely cease, it is required to select an alternative anesthetic which is validated for consistency with existing TGP data acquired under ether anesthesia. We therefore compared two alternative anesthetic candidates, isoflurane and pentobarbital, with ether in terms of hematological findings, serum biochemical parameters, and gene expressions. As a result, few differences among the three agents were observed. In hematological and serum biochemistry analysis, no significant changes were found. In gene expression analysis, four known genes were extracted as differentially expressed genes in the liver of rats anesthetized with ether, isoflurane, or pentobarbital. However, no significant relationships were detected using gene ontology, pathway, or gene enrichment analyses by DAVID and TargetMine. Surprisingly, although it was expected that the lung would be affected by administration via inhalation, only one differentially expressed gene was extracted in the lung. Taken together, our data indicate that there are no significant differences among ether, isoflurane, and pentobarbital with respect to effects on hematological parameters, serum biochemistry parameters, and gene expression. Based on its smallest affect to existing data and its safety profile for humans and animals, we suggest isoflurane as a suitable alternative anesthetic for use in rat euthanasia in toxicogenomics analysis.

Electroacupuncture Attenuates Anxiety-Like Behaviors in a Rat Model of Post-traumatic Stress Disorder: The Role of the Ventromedial Prefrontal Cortex

“…We made this substitution owing to the fact that ether is both explosive and known to be toxic in humans and other mammals. In prior studies, no differences in gene expression, hematological findings, or biochemical parameters were observed when comparing treatments with ether, pentobarbital, and isoflurane ( Nakatsu et al, 2017 ). Some researchers have reported that pentobarbital injection can induce additional stress that can interfere with cortisol levels in the plasma ( Wu et al, 2015 ), and acute pentobarbital administration in rats is associated with the impairment of spatial learning, memory, and hippocampal long-term potentiation ( Wang et al, 2015 ).…”

Pentose phosphate pathway activity parallels lipogenesis but not antioxidant processes in rat liver

“…In the experimental procedures of the present work, animals were briefly exposed to isoflurane anesthesia to minimize the discomfort associated with intraperitoneal injection of [U-13 C 3 ]glycerol. Isoflurane is generally acceptable in rat experiments without causing noticeable alterations in liver metabolism (6,20,21). However, continuously inhaled isoflurane with the use of bolus propofol anesthesia was reported to cause hepatic insulin resistance in dogs (17).…”

Tinospora cordifolia preserves pancreatic beta cells and enhances glucose uptake in adipocytes to regulate glucose metabolism in diabetic rats

“…In this study, we have used ether for euthanasia, which was reported to have an effect on inducing stress via releasing prolactin (Bodosi et al, ). However, a recent study has found that there are no significant differences among ether, isoflurane, and pentobarbital with respect to the effects on hematological parameters, serum biochemistry parameters, and gene expression (Nakatsu et al, ). Nevertheless, further studies are needed to fully understand the effect of different euthanasia inducers on the outcome of metabolic diseases.…”