Neuroprotective Effect of Etomidate in the Central Nervous System of Streptozotocin-Induced Diabetic Rats

Abstract

It is well known that hyperglycaemia due to diabetes mellitus leads to oxidative stress in the central nervous system. Oxidative stress plays important role in the pathogenesis of neurodegenerative changes. In the present study we investigated the possible neuroprotective effect of etomidate against streptozotocin-induced (STZ-induced) hyperglycaemia in the rat brain and spinal cord. A total of 40 rats were used in this study. Rats were divided into four groups: sham-control, diabetic, diabetic-etomidate treated and vehicle for etomidate treatment group. Diabetes mellitus was induced by a single injection of streptozotocin (60 mg/kg body weight). Three days after streptozotocin injection, etomidate (2 mg/kg) was injected intraperitoneally for etomidate group and lipid emulsion (10%) for vehicle group was injected with corresponding amount intraperitoneally every day for 6 weeks. Six weeks after streptozotocin injection, seven rats from each group were killed and brain, brain stem and cervical spinal cord were removed. The hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for the biochemical analysis (the level of malondialdehyde [MDA], total nitrite, reduced glutathione [GSH], and xanthine oxidase [XO] activity). STZ-induced diabetes resulted in significantly elevation of MDA, XO and nitrite levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the rats (P < 0.05) while etomidate treatment provided significantly lower values (P < 0.05). This study demonstrated that etomidate have neuroprotective effect on the neuronal tissue against the diabetic oxidative damage.

Increase of cannabinoid CB1 receptor density in the hippocampus of streptozotocin-induced diabetic rats

“…One striking aspect of our study was the observed disparity between changes in the expression and the density of CB 1 Rs after STZ treatment. This suggests either a modification of protein translation, as was reported to occur in the hippocampus after traumatic brain injury (Chen et al, in press), where activation of a key rate-limiting translational pathway (the mTOR pathway) is observed; or alternatively a modification of the half-life of CB 1 Rs that might be related to oxidative stress found in the hippocampus of STZinjected rats (Ates et al, 2006). In conclusion, the elevated density of the CB 1 R protein and CB 1 R binding sites may represent a compensatory or a pathophysiological process.…”

Neuromodulatory Effects of Hesperidin in Mitigating Oxidative Stress in Streptozotocin Induced Diabetes

“…Evidence has accumulated showing the massive generation of reactive free radicals in diabetes and the resulting increase in LPO and protein oxidation which leads to cellular disintegrity of neuron [28, 29]. Lipid peroxides and protein oxidation are the secondary products of oxidative stress causing secondary injury by further generating relatively more stable and diffusible cytotoxic agents such as malondialdehyde and 4-hydroxy-trans-2-nonenal, respectively, and magnifying oxidative stress [30].…”

Reduced Hippocampal Cell Differentiation in the Subgranular Zone of the Dentate Gyrus in a Rat Model of Type II Diabetes

“…The male ZDF rat (ZDF/Gmi, fa/fa), derived from inbreeding of hyperglycemic Zucker obese rats, is characterized by a mutation in the leptin receptor with resultant high circulating leptin levels. Diabetes mellitus is associated with cerebral alterations in both human and animal models of the disease [4][5][6][7]. Hippocampal neurons are also sensitive to the effects of diabetes [6,8] and often show damage to presynaptic and postsynaptic structures, dysregulation of calcium homeostasis, neuronal loss, dendritic atrophy in CA3 neurons, reduced expression of insulin growth factors and their receptors, and decreased neurogenesis [8][9][10][11][12].…”