Central administration of tert-butylhydroquinone attenuates hypertension via regulating Nrf2 signaling in the hypothalamic paraventricular nucleus of hypertensive rats.

Reactive oxygen species (ROS) in the paraventricular nucleus (PVN) play a pivotal role in the pathogenesis of hypertension. Nuclear factor E2-related factor-2 (Nrf2) is an important transcription factor that modulates cell antioxidant defense response against oxidative stress. The present study aimed to explore the efficacy of PVN administration of tert-butylhydroquinone (tBHQ), a selective Nrf2 activator, in hypertensive rats. 16-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used in this study. These rats were chronic bilateral PVN infusion of tBHQ (0.8µg/day), or oxygen free radical scavenger tempol (20µg/h), or vehicle for 2weeks. SHR rats had higher mean arterial pressure (MAP), plasma norepinephrine (NE) levels, and sympathetic nerve activity (RSNA) and lower PVN levels of Nrf2, hemeoxygenase-1 (HO-1), superoxide dismutase-1 (SOD1) and catalase (CAT) as compared with those in the WKY group. Bilateral PVN infusion of tBHQ or tempol significantly reduced MAP, RSNA, plasma NE levels in SHR rats. In addition, tBHQ treatment enhanced the nuclear accumulation of Nrf2 and increased the expression of HO-1, CAT and SOD1 in SHR rats. Furthermore, tBHQ attenuated PVN levels of ROS, the expression of proinflammatory cytokines and restored the imbalance of neurotransmitters in PVN. Knockdown of Nrf2 in the PVN by adeno-associated virus mediated small interfering RNA abrogated the protective effects of tBHQ on hypertension. These findings suggest that PVN administration of tBHQ can attenuate hypertension by activation of the Nrf2-mediated signaling pathway.

Protective effect of propofol on noise-induced hearing loss.

PURPOSE: Iatrogenic noise produced by mastoid or craniotomy drills may cause hearing damage, which is induced by the generation of reactive oxygen species (ROS) and the reduction of cochlear blood flow (CoBF). This study investigated whether propofol could reduce noise-induced hearing loss (NIHL) in a guinea pig model. METHODS: Sixty-four male pigmented guinea pigs were randomly and equally divided into 4 groups: control, noise, propofol and propofol+noise. Propofol was infused intravenously for 20min prior to noise exposure with a loading dose of 5mg·kg-1 for 5min and a maintenance infusion of 20mg·kg-1·h-1 for 135min. For noise exposure, an octave band noise at a 124dB sound pressure level (SPL) was administered to animals for 2h. The mean arterial pressure (MAP) and CoBF were monitored continuously. Auditory function was measured by the level of distortion product otoacoustic emission (DPOAE) before and at 1h, 72h and 240h after noise exposure. Cochlear levels of 8-iso-Prostaglandin F2alpha (8-iso-PGF2α) were measured immediately after the termination of noise exposure. Cochlear silver nitrate staining and outer hair cell (OHC) counting were performed after the final functional test. RESULTS: Noise exposure caused decreases in the CoBF and DPOAE amplitudes, over-generation of 8-iso-PGF2α and the loss of OHCs. Pre-treatment with propofol significantly increased the CoBF and DPOAE amplitudes, decreased 8-iso-PGF2α and the loss of OHCs. CONCLUSIONS: Propofol exerted protective effects against NIHL in this animal model by suppressing a lipid peroxidation reaction and improving CoBF.

[Effect of metallothionein on myocyte apoptosis and energy supply of isolated rabbit heart muscle during perfusion with ropivacaine].

OBJECTIVE: [corrected] To assess the effects of metallothionein on myocyte apoptosis and energy supply of isolated rabbit heart muscle during perfusion with ropivacaine.. METHODS: Sixty New Zealand white male rabbits were randomized into 3 equal groups. In group I, the rabbits received a intreaperitioneal injection of distilled water 24 h before isolation of the heart with perfusion by Langendoff model; in group II, distilled water was injected intreaperitioneally, and 24 h later the heart was isolated and perfused with Langendoff model and ropivacaine; in group III, 3.6% ZnSO(4) was injected intreaperitioneally and the isolated heart was perfused with Langendoff model and ropivacaine. The myocardial metallothionein content, myocyte apoptosis, and myocardial ATP, ADP and AMP content were detected. RESULTS: The myocardial metallothionein content was significantly higher in group III than in the other two groups; the percent of myocyte apoptosis was the highest in group II, and was significantly higher in group III than in group I. The myocardial content of ATP was the highest in group I, and was significantly higher in group III than in group II. CONCLUSION: Metallothionein can significantly inhibit myocyte apoptosis and alleviate energy supply disorder induced by ropivacaine.

[Effect of low dose propofol on biological behavior of esophageal squamous cell carcinoma cell line Eca109].

AIM: To detect the effect of low dose propofol on the proliferation, apoptosis, migration, and invasion of esophageal squamous cell carcinoma cell line Eca109. METHODS: The proliferation, apoptosis, migration, and invasion of esophageal squamous cell carcinoma cell line Eca109 were detected by MTT assay, flow cytometry, transwell assay respectively. The effect of low dose propofol on expression of heme oxygenase-1 (HO-1) was confirmed by Real-time quantitative PCR. RESULTS: Low dose propofol could inhibit the proliferation, migration, invasion and promate the apoptosis of esophageal squamous cell carcinoma cell line Eca109. And low dose propofol increased the expression of HO-1 mRNA in a dose-dependment manner. CONCLUSION: Low dose propofol affects the biological behavior of esophageal squamous cell carcinoma cell line Eca109, which has a relationship with increasing the expression of HO-1.

Midazolam in rabbits terminates dysrhythmias caused by intracerebroventricular ropivacaine.

The current study was designed to investigate the mechanisms by which ropivacaine may act within the central nervous system (CNS) to produce cardiotoxicity. Eighty New Zealand rabbits were divided into four groups randomly. In Group 1, 20 rabbits received intracerebroventricular (icv) saline, and then received icv ropivacaine 30 min later. In Group 2, 20 rabbits received icv ropivacaine. Whenever dysrhythmias continued for more than 5 min, 0.1 ml saline was administered into the left cerebral ventricle. Ten minutes later, 0.1 ml midazolam was given into the left lateral ventricle. In Group 3, 20 rabbits received icv ropivacaine, and once the dysrhythmias developed, the inspired isoflurane concentration was increased from 0.75% to 1.50%. In Group 4, 20 animals received an intravenous (iv) phenylephrine infusion until dysrhythmias occurred. In Group 1, the rabbits did not develop dysrhythmias in response to icv saline, whereas dysrhythmias did develop in these animals after icv ropivacaine. In Group 2, icv saline had no effect on the dysrhythmias; however, icv midazolam terminated cardiac dysrhythmias. In Group 3, an increase in the concentration of the inspired isoflurane had no effect on dysrhythmias. In Group 4, icv midazolam had no effect on dysrhythmias in response to iv phenylephrine. Ropivacaine administered directly into the CNS is capable of producing cardiac dysrhythmias; midazolam terminated dysrhythmias presumably by potentiation of γ-aminobutyric acid (GABA) receptor activity. Our results suggest that ropivacaine produces some of its cardiotoxicity not only by the direct cardiotoxicity of the drug, but also by the CNS effects of ropivacaine.