scholarly journals Protective effects and mechanisms of high-dose vitamin C on sepsis-associated cognitive impairment in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ning Zhang ◽  
Wei Zhao ◽  
Zhen-Jie Hu ◽  
Sheng-Mei Ge ◽  
Yan Huo ◽  
...  

AbstractSepsis survivors present long-term cognitive deficits. The present study was to investigate the effect of early administration of high-dose vitamin C on cognitive function in septic rats and explore its possible cerebral protective mechanism. Rat sepsis models were established by cecal ligation and puncture (CLP). Ten days after surgery, the Morris water maze test was performed to evaluate the behavior and cognitive function. Histopathologic changes in the hippocampus were evaluated by nissl staining. The inflammatory cytokines, activities of antioxidant enzymes (superoxide dismutase or SOD) and oxidative products (malondialdehyde or MDA) in the serum and hippocampus were tested 24 h after surgery. The activity of matrix metalloproteinase-9 (MMP-9) and expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) in the hippocampus were measured 24 h after surgery. Compared with the sham group in the Morris water maze test, the escape latency of sepsis rats was significantly (P = 0.001) prolonged in the navigation test, whereas the frequency to cross the platform and the time spent in the target quadrant were significantly (P = 0.003) reduced. High-dose vitamin C significantly decreased the escape latency (P = 0.01), but increased the time spent in the target quadrant (P = 0.04) and the frequency to cross the platform (P = 0.19). In the CLP+ saline group, the pyramidal neurons were reduced and distributed sparsely and disorderly, the levels of inflammatory cytokines of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the serum and hippocampus were significantly increased (P = 0.000), the blood brain barrier (BBB) permeability in the hippocampus was significantly (P = 0.000) increased, the activities of SOD in the serum and hippocampus were significantly (P = 0.000 and P = 0.03, respectively) diminished while the levels of MDA in the serum and hippocampus were significantly (P = 0.007) increased. High-dose vitamin C mitigated hippocampus histopathologic changes, reduced systemic inflammation and neuroinflammation, attenuated BBB disruption, inhibited oxidative stress in brain tissue, and up-regulated the expression of nuclear and total Nrf2 and HO-1. High-dose vitamin C significantly (P < 0.05) decreased the levels of tumor necrosis factor- (TNF)-α, interleukin-6 (IL-6), MDA in the serum and hippocampus, and the activity of MMP-9 in the hippocampus, but significantly (P < 0.05) increased the levels of SOD, the anti-inflammatory cytokine (IL-10) in the serum and hippocampus, and nuclear and total Nrf2, and HO-1 in the hippocampus. In conclusion, high-dose vitamin C can improve cognition impairment in septic rats, and the possible protective mechanism may be related to inhibition of inflammatory factors, alleviation of oxidative stress, and activation of the Nrf2/HO-1 pathway.

Author(s):  
Pankaj Phukan ◽  
Sanjit Namasudra ◽  
Meenakshi Bawari ◽  
Mahuya Sengupta

Objective: The aim of this study was to evaluate the effects of aqueous extract of dry fruits of Trapa bispinosa (TB) in alleviating mercury (Hg)-induced neurobehavioral toxicity.Methods: A total of 36 adult male Swiss albino mice weighing 25–30 g were equally divided into six groups, namely I–VI. Group I received distilled water, Group II received mercuric chloride (1.5 mg/kg), Group III received TB extract low dose (150 mg/kg), Group IV received TB extract high dose (300 mg/kg), Group V received mercuric chloride plus TB extract low dose, and Group VI received mercuric chloride plus TB extract high dose. All the groups received doses orally through oral gavage tube and the treatment lasted for 14 days. The behavioral effects were evaluated with locomotor activity in the open field test (OFT), spatial learning ability and memory in the Morris water maze test (MWM), immobility in Forced swimming test (FST) and anxiety in Elevated plus maze test (EPM).Result: In the present study, it was observed that Hg-exposed mice significantly decreased the locomotor activity (p<0.001), time spent in open arms (p<0.001), number of open arm entries (p<0.01), number of annulus crossovers (p<0.001) and increased immobility (p<0.001), escape latency (p<0.01), and path length (p<0.001) in mice. The aqueous extract of TB significantly reduced the neurotoxic effects of Hg. The aqueous extract of TB showed to increase the locomotor activity (p<0.01), time spent in open arms (p<0.01), number of open arm entries (p<0.05), and number of annulus crossovers (p<0.001), which was decreased in Hg-exposed mice. TB extract also showed to decrease the immobility (p<0.001), escape latency (p<0.05), and path length (p<0.001) in Hg-fed mice.Conclusion: On the basis of the results obtained from the behavioral study, the present study indicates that mercuric chloride caused neurobehavioral changes which were significantly reversed by the aqueous extract of TB. Thus, TB was found to be effective in ameliorating the neurobehavioral deficit induced by Hg exposure.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3442
Author(s):  
Yaowared Chulikhit ◽  
Wichitsak Sukhano ◽  
Supawadee Daodee ◽  
Waraporn Putalun ◽  
Rakvajee Wongpradit ◽  
...  

The effects of the phytoestrogen-enriched plant Pueraria mirifica (PM) extract on ovari-ectomy (OVX)-induced cognitive impairment and hippocampal oxidative stress in mice were investigated. Daily treatment with PM and 17β-estradiol (E2) significantly elevated cognitive behavior as evaluated by using the Y maze test, the novel object recognition test (NORT), and the Morris water maze test (MWM), attenuated atrophic changes in the uterus and decreased serum 17β-estradiol levels. The treatments significantly ameliorated ovariectomy-induced oxidative stress in the hippocampus and serum by a decrease in malondialdehyde (MDA), an enhancement of superoxide dismutase, and catalase activity, including significantly down-regulated expression of IL-1β, IL-6 and TNF-α proinflammatory cytokines, while up-regulating expression of PI3K. The present results suggest that PM extract suppresses oxidative brain damage and dysfunctions in the hippocampal antioxidant system, including the neuroinflammatory system in OVX animals, thereby preventing OVX-induced cognitive impairment. The present results indicate that PM exerts beneficial effects on cognitive deficits for which menopause/ovariectomy have been implicated as risk factors.


Redox Biology ◽  
2021 ◽  
Vol 43 ◽  
pp. 101980
Author(s):  
Andree G. Pearson ◽  
Juliet M. Pullar ◽  
John Cook ◽  
Emma S. Spencer ◽  
Margreet CM. Vissers ◽  
...  

2012 ◽  
Vol 64 (4) ◽  
pp. 367-371 ◽  
Author(s):  
Khalid K. Abdul-Razzak ◽  
Karem H. Alzoubi ◽  
Salah A. Abdo ◽  
Wael M. Hananeh

2000 ◽  
Vol 21 ◽  
pp. S157
Author(s):  
H. Tanaka ◽  
T. Tokunaga ◽  
H. Matsuda ◽  
S. Shimazaki

2015 ◽  
Vol 147 (2) ◽  
pp. 350-359 ◽  
Author(s):  
Keunyoung Kim ◽  
Ok-Nam Bae ◽  
Sung-Hee Koh ◽  
Seojin Kang ◽  
Kyung-Min Lim ◽  
...  

1998 ◽  
Vol 19 ◽  
pp. S200
Author(s):  
H Tanaka ◽  
T Matsuda ◽  
T Yukioka ◽  
H Matsuda ◽  
S Shimazaki

Author(s):  
Jing Zhang ◽  
Xin Rao ◽  
Yiming Li ◽  
Yuan Zhu ◽  
Fang Liu ◽  
...  

Abstract BackgroundNo specific medication has been proven effective for the treatment of patients with severe coronavirus disease 2019 (COVID-19). Here, we tested whether high-dose vitamin C infusion was effective for severe COVID-19.MethodsThis randomized, controlled clinical trial was performed at 3 hospitals in Hubei, China. Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the ICU were randomly assigned in as 1:1 ratio to either the high-dose intravenous vitamin C (HDIVC) or the placebo. HDIVC group received 12 g of vitamin C/50 ml every 12 hours for 7 days at a rate of 12 ml/hour, and the placebo group received bacteriostatic water for injection in the same way. The primary outcome was invasive mechanical ventilation-free days in 28 days(IMVFD28). Secondary outcomes were 28-day mortality, organ failure, and inflammation progression.ResultsFifty-four critical COVID-19 patients were ultimately recruited. There was no difference in IMVFD28 between two groups. During the 7-day treatment period, patients in the HDIVC group had a steady rise in the PaO2/FiO2 (day 7: 229 vs. 151 mmHg, 95% CI 33 to 122, P = 0.01). Patients with SOFA scores ≥ 3 in the HDIVC group exhibited a significant reduction in 28-day mortality (P = 0.05) in univariate survival analysis. IL-6 in the VC group was lower than that in the placebo group (19.42 vs. 158.00; 95% CI -301.72 to -29.79; P = 0.04) on day 7.ConclusionThe addition of HDIVC may provide a protective clinical effect without any adverse events in critically ill patients with COVID-19.Clinicaltrial.gov identifer: NCT04264533


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