Effect of sevoflurane on iron homeostasis and toxicity in the brain of mice

Wang, Meiyue; Zuo, Yong; Li, Xincheng; Li, Yan; Thirupathi, Anand; Yu, Peng; Gao, Guofen; Zhou, Changle; Chang, Yan‐Zhong; Shi, Zhenhua

doi:10.1016/j.brainres.2021.147328

Cited by 17 publications

(26 citation statements)

References 36 publications

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“…This study showed a new mechanism that cross-dysregulation of iron and glucose metabolism played an important role in cognitive impairment induced by Sev in mice. Based on our results here and combined with our previous research work [ 19 , 31 ], we summarized the possible mechanism of nerve injury induced by sevoflurane as shown in Figure 9 .…”

Section: Discussionmentioning

confidence: 59%

“…Our previous study had reported that Sev could cause iron accumulation in brain in 15-month old mice [ 19 ]. However, we also found Sev-induced cognitive impairment in the offspring caused by iron deficiency during pregnancy in mice [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

“…We recently completed the work demonstrating that sevoflurane causes brain iron deficiency, inhibits myelin development, and induces cognitive impairment in the offspring of pregnant mice [ 20 ]. However, our recent and others study have shown that Sev can cause cognitive impairment by inducing the iron overload in brain in 12-month-old mice [ 19 , 23 ]. This suggests that Sev has different effects on iron metabolism in mice of different ages.…”

Section: Discussionmentioning

confidence: 99%

“…A total of sixty 15-month-old C57BL/6 male mice were assigned into two groups: control group and Sev treatment group. Anesthesia treatment of mice was according to the previous report [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

“…We used MWM to test the capacity of the mouse to learn and memory according to the previous report [ 19 ]. Briefly, for mice in control group, each mouse was given swimming training one time a day for 6 days.…”

Section: Methodsmentioning

confidence: 99%

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A new mechanism of POCD caused by sevoflurane in mice: cognitive impairment induced by cross-dysfunction of iron and glucose metabolism

Zuo

Jinhong

et al. 2021

Aging

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Sevoflurane (Sev) is a commonly used anesthetic in hospitals that can cause neurotoxicity. Postoperative cognitive dysfunction (POCD) is a common clinical problem induced by some anesthetics. However, the exact mechanism of neurotoxicity induced by Sev is unclear. Here we studied a new mechanism of POCD induced by Sev. We treated 15-month-old mice with 2% Sev for 6 hours, and we had found that Sev causes POCD. Using isobaric tags for relative and absolute quantitation (iTRAQ), we found that the transporter and the metabolism of carbohydrates and inorganic ions were involved in the cognitive impairment induced by Sev. Using synchrotron radiation micro-X-ray fluorescence (μ-XRF), we showed that Sev caused the iron overload in the brain of 15-month-old mice. Subsequently, excessive iron led to oxidative stress and impaired mitochondrial function that further led to glucose metabolism disorder and reduced ATP production by regulating the expression of key enzyme genes or proteins including G6Pase, Pck1, and Cs. Meanwhile, Sev also inhibited the oxygen consumption rate and glucose absorption by downregulating the expression of glucose transporter 1 in cerebral vascular endothelial cells. The cross-dysfunction of iron and glucose metabolism caused the apoptosis in the cortex and hippocampus through Bcl2/Bax pathway. In conclusion, the data here showed a new mechanism that Sev caused apoptosis by cross-dysregulation of iron and glucose metabolism and induced energy stress in mice. Maintaining iron and glucose metabolism homeostasis may play an important role in cognitive impairment induced by Sev.

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Section: Discussionmentioning

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A new mechanism of POCD caused by sevoflurane in mice: cognitive impairment induced by cross-dysfunction of iron and glucose metabolism

Zuo

Jinhong

et al. 2021

Aging

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Liproxstatin‐1 alleviates ferroptosis in sevoflurane anesthesia‐induced cognitive deficits of aged mice: The role oxidative stress

Li,

Chen,

Wang

et al. 2024

Synapse

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In this study, we aimed to validate the hypothesis that the interplay between sevoflurane, oxidative stress and ferroptosis is crucial for the pathogenesis of sevoflurane‐induced cognitive impairment in aged individuals. The mice with sevoflurane‐induced cognitive impairment were used to explore the effects of sevoflurane on oxidative stress, iron homeostasis, and cognitive function in aged mice. Iron content and oxidative stress markers were analyzed in hippocampal tissue homogenates using specific assays. Additionally, the levels of iron death‐related markers (Fth1 and Gpx4) were assessed by real‐time PCR and Western blotting. Morris Water Maze and novel object recognition (NOR) tests were conducted to evaluate cognitive function. Sevoflurane exposure in aged mice resulted in a significant increase in iron overloading in the hippocampus, followed by a subsequent stabilization. Oxidative stress levels were elevated in the hippocampal tissue of sevoflurane‐exposed mice, and a significant correlation was observed between iron death and oxidative stress. Liproxstatin‐1, a ferroptosis inhibitor, effectively ameliorated the decline in memory and learning abilities induced by sevoflurane anesthesia. Liproxstatin‐1 treatment reduced iron overload and oxidative stress in the hippocampal tissue of aged mice. The expression of Fth1 and Gpx4, iron death‐related markers, was downregulated following Liproxstatin‐1 intervention. Our findings suggest that sevoflurane anesthesia disrupts iron homeostasis, leading to increased oxidative stress and cognitive impairment in aged mice. These results highlight the potential of targeting iron‐mediated processes to mitigate sevoflurane‐induced cognitive impairment in the aging population.

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Effects of exposure to the inhalational anaesthetic sevoflurane on the male reproductive system in rats

Liu

Zhang

et al. 2023

Veterinary Medicine & Sci

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Objectives:The purpose of this study was to explore the effects of inhalational anaesthetics on the male reproductive system in neonatal rats.Methods: Postnatal day 6 (P6) male rat pups were assigned to 2 groups of 40 rats each. The control group did not receive anaesthesia, and the test group was exposed to air containing 3% sevoflurane in a chamber. After sevoflurane exposure, the effects on the male reproductive system in neonatal rats exposed to inhalational anaesthetics were tested. The rats were maintained to P60. The fertility, sperm and spermatid count, sperm motility, organ weights and histological changes in rats were determined.Results: Compared with those of the control group, the sperm count and motility of the sevoflurane group were significantly decreased (p < 0.05), and there was also a decrease in the number of foetal rats from the sevoflurane group (p < 0.05). Furthermore, the arrangement of the seminiferous tubule was regular in the control group, whereas the arrangement of the seminiferous tubule was distorted and the spermatocytes were detached and irregularly lined in the sevoflurane group. TUNEL analysis showed that the number of apoptotic cells in the testes of the sevoflurane group was significantly increased (p < 0.05). SOD and MDA analyses showed that SOD was decreased, while MDA expression was increased.Conclusions: These data indicated that young rats suffered as a result of inhalation of the anaesthetic sevoflurane and had reduced reproductive system function during adolescence in males. These studies are useful as a foundation for clinical studies.

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Effect of sevoflurane on iron homeostasis and toxicity in the brain of mice

Cited by 17 publications

References 36 publications

A new mechanism of POCD caused by sevoflurane in mice: cognitive impairment induced by cross-dysfunction of iron and glucose metabolism

A new mechanism of POCD caused by sevoflurane in mice: cognitive impairment induced by cross-dysfunction of iron and glucose metabolism

Liproxstatin‐1 alleviates ferroptosis in sevoflurane anesthesia‐induced cognitive deficits of aged mice: The role oxidative stress

Effects of exposure to the inhalational anaesthetic sevoflurane on the male reproductive system in rats

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