Investigation of Dose-Dependent Tissue Protective Effects of Vitamin C

AbstractThe sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3−/− or Mlkl−/− mice, respectively) and assessed the roles of necroptosis in AP. We found that Ripk3−/− mice had significantly more severe pancreatic edema and inflammation associated with macrophage and neutrophil infiltration than control mice. Consistently, Mlkl−/− mice were more susceptible to caerulein-induced AP, which occurred in a time- and dose-dependent manner, than control mice. Mlkl−/− mice exhibit weight loss, edematous pancreatitis, necrotizing pancreatitis, and acinar cell dedifferentiation in response to tissue damage. Genetic deletion of Mlkl resulted in downregulation of the antiapoptotic genes Bclxl and Cflar in association with increases in the numbers of apoptotic cells, as detected by TUNEL assay. These findings suggest that RIPK3 and MLKL-mediated necroptosis exerts protective effects in AP and caution against the use of necroptosis inhibitors for AP treatment.

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Long Noncoding RNA SPRY4-IT1 Modulates Ketamine-Induced Neurotoxicity in Human Embryonic Stem Cell-Derived Neurons through EZH2

Developmental Neuroscience ◽

10.1159/000513535 ◽

2021 ◽

pp. 1-9

Author(s):

Jingyuan Huang ◽

Yan Xu ◽

Fang Wang ◽

Haili Wang ◽

Lu Li ◽

...

Keyword(s):

Long Noncoding Rna ◽

Noncoding Rna ◽

Embryonic Stem ◽

Protective Effects ◽

Tyrosine Kinase Signaling ◽

Ezh2 Expression ◽

Induced Neurons ◽

Neurite Degeneration ◽

Dose Dependent

Objective: This study aimed to investigate whether long noncoding RNA sprouty receptor tyrosine kinase signaling antagonist 4-intronic transcript 1 (SPRY4-IT1) is involved in the regulation of ketamine-induced neurotoxicity. Methods: Human embryonic stem cells (hESCs) were induced into neurons in vitro and treated with ketamine. Apoptosis and neurite degeneration assays were used to determine ketamine-induced neurotoxicity and qRT-PCR to determine SPRY4-IT1 expression. SPRY4-IT1 was downregulated in hESC-induced neurons to examine its regulation on ketamine-induced neurotoxicity. The correlation between enhancer of zeste homolog 2 (EZH2) and SPRY4-IT1 was also examined. EZH2 was upregulated in SPRY4-IT1-downregualted hESC-induced neurons to further examine its participation in SPRY4-IT1-mediated ketamine neurotoxicity. Results: Ketamine-induced dose-dependent apoptosis, neurite degeneration, and SPRY4-IT1 upregulation in hESC-induced neurons. Lentivirus-mediated SPRY4-IT1 downregulation protected ketamine neurotoxicity. EZH2 expression was positively correlated with SPRY4-IT1 in hESC-induced neurons. EZH2 overexpression markedly reversed the protective effects of SPRY4-IT1 knockdown on ketamine neurotoxicity. Conclusions: SPRY4-IT1 is involved in anesthesia-induced neurotoxicity, possibly through the regulation on EZH2 gene.

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The Potential Use of Vitamin C to Prevent Kidney Injury in Patients with COVID-19

Diseases ◽

10.3390/diseases9030046 ◽

2021 ◽

Vol 9 (3) ◽

pp. 46

Author(s):

Feng Xu ◽

Yawei Wen ◽

Xinge Hu ◽

Tiannan Wang ◽

Guoxun Chen

Keyword(s):

Vitamin C ◽

Distress Syndrome ◽

Kidney Injury ◽

Mortality Rates ◽

Protective Effects ◽

Global Public Health ◽

Health Crisis ◽

Public Health Crisis ◽

Renal Functions ◽

Potential Use

The newly found SARS-CoV-2 has led to the pandemic of COVID-19, which has caused respiratory distress syndrome and even death worldwide. This has become a global public health crisis. Unfortunately, elders and subjects with comorbidities have high mortality rates. One main feature of COVID-19 is the cytokine storm, which can cause damage in cells and tissues including the kidneys. Here, we reviewed the current literature on renal impairments in patients with COVID-19 and analyzed the possible etiology and mechanisms. In addition, we investigated the potential use of vitamin C for the prevention of renal injury in those patients. It appears that vitamin C could be helpful to improve the outcomes of patients with COVID-19. Lastly, we discussed the possible protective effects of vitamin C on renal functions in COVID-19 patients with existing kidney conditions.

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Effects of Propentofylline on Hypoxia—Hypoglycemia-Induced Calcium Accumulation in Gerbil Hippocampal Slices

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1992.41 ◽

1992 ◽

Vol 12 (2) ◽

pp. 301-305 ◽

Cited By ~ 12

Author(s):

Fumito Kadoya ◽

Akira Mitani ◽

Tatsuru Arai ◽

Kiyoshi Kataoka

Keyword(s):

Cerebral Ischemia ◽

Intracellular Calcium ◽

Neuronal Damage ◽

Hippocampal Slices ◽

Dependent Manner ◽

Protective Effects ◽

Calcium Accumulation ◽

Xanthine Derivative ◽

Acute Increase ◽

Dose Dependent

The xanthine derivative propentofylline (HWA 285) has been reported to show protective effects against neuronal damage induced by cerebral ischemia. In the present study, microfluorometry was used to investigate the effect of propentofylline on the hypoxia–hypoglycemia-induced intracellular calcium accumulation in gerbil hippocampal slices. When slices were superfused with hypoxic–hypoglycemic medium that did not contain propentofylline, an acute increase in calcium accumulation was detected 75–200 s (mean latency of 123 s) after the beginning of hypoxia–hypoglycemia. When slices were superfused with hypoxic–hypoglycemic mediums that contained 10 μ M, 100 μ M, and 1 m M propentofylline, the latency of the acute increase in calcium accumulation was prolonged in all subregions of the hippocampus in a dose-dependent manner: mean latencies in field CA1 were 146, 168, and 197 s after hypoxia–hypoglycemia, respectively. This retardation in calcium accumulation may be involved in the mechanisms by which propentofylline diminishes ischemic injury.

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Protective effects of Vitamin C on cisplatin nephrotoxicity

Archives of Pharmacal Research ◽

10.1007/bf02978240 ◽

1994 ◽

Vol 17 (1) ◽

pp. 11-16 ◽

Cited By ~ 1

Author(s):

Se-Young Choung ◽

Jae-Myeong Kong

Keyword(s):

Vitamin C ◽

Protective Effects ◽

Cisplatin Nephrotoxicity

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Antioxidative properties of Sambacus nigra extracts

Chemical Papers ◽

10.1515/chempap-2015-0138 ◽

2015 ◽

Vol 69 (9) ◽

Cited By ~ 3

Author(s):

Dominika Topoľská ◽

Katarína Valachová ◽

Peter Rapta ◽

Stanislav Šilhár ◽

Elena Panghyová ◽

...

Keyword(s):

Acute Inflammation ◽

Radical Scavenging ◽

Oxidative Degradation ◽

Protective Effects ◽

Radical Scavenging Capacity ◽

Scavenging Capacity ◽

Diammonium Salt ◽

Dose Dependent ◽

Oxidative System

AbstractPotential protective effects of elderberry (Sambucus nigra) extracts against oxidative degradation of hyaluronan (HA) were detected in vitro. To induce free-radical-mediated HA degradation, Weissberger’s biogenic oxidative system, which mimics the situation of acute inflammation, was applied. Time- and dose-dependent changes of dynamic viscosity of the HA solutions in the presence and absence of two elderberry extracts produced in 2006 and 2012 were recorded by rotational viscometry (RV). Radical scavenging capacity of both extracts was investigated by the spectrocolorimetric ABTS [2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt] assay and the “inverted” ABTS assay. Oxygen consumption of the system oxidizing HA either in the absence or presence of the elderberry extracts was determined. The results of RV revealed that an addition of the newer extract (2012) promoted the inhibition of HA degradation more markedly compared to the older extract (2006). The same effect of both extracts on ABTS

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Protective role of vitamins A, C, and E against the genotoxic damage induced by aflatoxin B1 in cultured human lymphocytes

Toxicology and Industrial Health ◽

10.1177/0748233709106068 ◽

2009 ◽

Vol 25 (3) ◽

pp. 183-188 ◽

Cited By ~ 12

Author(s):

L Alpsoy ◽

G Agar ◽

M Ikbal

Keyword(s):

Vitamin A ◽

Vitamin C ◽

Human Lymphocytes ◽

Mutagenic Effect ◽

Treated Group ◽

Protective Role ◽

Effective Concentration ◽

Dependent Manner ◽

Protective Effects ◽

Aflatoxin B

In this study, we aimed to evaluate the effect of vitamins A, C, and E against aflatoxin B1 (AFB1) on blood cultures in relation to induction of sister chromatid exchange (SCE). The results indicated genotoxic and mutagenic damage in cultured human lymphocytes exposed to AFB1. The results showed that 5 μM concentration of AFB1 increased SCE. When vitamins A, C, and E were added to AFB1, the frequency of SCE decreased. These results suggest that vitamins A, C, and E could effectively inhibit AFB1-induced SCE, which may partially responsible for its mutagenic effect of AFB1. Besides, the protective effect of vitamins A, C, and E against AFB1 was increased in a dose-dependent manner (i.e., as the doses increased, their protective effects also increased). There was a significant decrease in the SCE frequency in AFB1-treated group compared with the groups receiving AFB1 and also vitamins A, C, and E. The most effective concentration was 100 microM vitamin C, and the lowest effective concentration was 0.5 microM vitamin A. Vitamin C has the most effective concentration of 100 μM, and vitamin A has the lowest effective concentration of 0.5 μM. The order of the decreasing effect of the SCE frequency of vitamins was as follows: vitamin C > vitamin E > vitamin A.

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Hepatoprotective effects of Sapium sebiferum in paracetamol-induced liver injury

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i2.22576 ◽

2015 ◽

Vol 10 (2) ◽

pp. 393 ◽

Cited By ~ 3

Author(s):

Liaqat Hussain ◽

Muhammad Sajid Hamid Akash ◽

Madeha Tahir ◽

Kanwal Rehman

Keyword(s):

Liver Injury ◽

Serum Levels ◽

Therapeutic Effects ◽

Sapium Sebiferum ◽

Dependent Manner ◽

Protective Effects ◽

Drug Induced ◽

Standard Drug ◽

Hepatoprotective Effects ◽

Dose Dependent

Sapium sebiferum leaves were used to determine its hepatoprotective effects against paracetamol-induced hepatotoxicity in mice. A dose dependent study was conducted using two different doses (200 mg/kg and 400 mg/kg) of the extract of S. sebiferum against toxic effects of paracetamol (500 mg/kg) in experimental animal model. Silymarin (50 mg/kg) was used as standard drug to compare therapeutic effects of S. sebiferum with control and paracetamol-treated groups. Paracetamol significantly increased the serum levels of liver enzyme markers like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin. The extract showed protective effects by normalizing the liver enzymes markers in a dose dependent manner. Histopathological results confirmed the hepatoprotective effects of leaves of S. sebiferum. We conclude that leaves of S. sebiferum have strong hepatoprotective effects against paracetamol-induced liver injury and can be used in liver injuries caused by drug-induced toxicity.

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Effect of vitamin C supplementation on hematological parameters in smokeless tobacco chewers

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v12i3.4819 ◽

2021 ◽

Vol 12 (3) ◽

pp. 2088-2094

Author(s):

Jaywant S. Thorat ◽

Anand G. Joshi ◽

Kanchan C. Wingkar

Keyword(s):

Platelet Count ◽

Vitamin C ◽

Smokeless Tobacco ◽

Hematological Parameters ◽

Protective Effects ◽

Baseline Study ◽

Vitamin C Supplementation ◽

Baseline Values ◽

Wbc Count ◽

Rbc Count

The present study was aimed to evaluate the effect of Vitamin C (VC) supplementation on hematological parameters in Smokeless Tobacco (ST) chewers. A total of 338 subjects aged between 31 to 60 years (168 ST chewers and 170 ST non-chewers) participated in the present study. ST chewers were further divided into 3 subgroups with respect to ST chewing duration in years. Subjects of both the groups were examined at the baseline study and after 45 days of supplementation of 1 g of Vitamin C (VC) for hematological parameters. WBC count (p=0.04), granulocytes % (p=0.0007), HCT (p=0.01) and MCV (p=0.04) were significantly increased whereas, monocytes % (p=0.002) and platelet count (p<0.0001) were significantly decreased in ST chewers as compared to controls. After supplementation of VC, WBC count (p<0.001) and granulocytes % (p<0.0001) were significantly decreased and lymphocytes % (p=0.008), monocytes % (p<0.0001), RBC count (p=0.01) and Hb content (p=0.006) were significantly increased in ST chewers as compared to their baseline values. In conclusion, the use of ST had deleterious effects on hematological parameters; however, supplementation of 1 g of VC showed protective effects on hematological parameters.

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