Protective effects of fomepizole on 2-chloroethanol toxicity

2010 ◽  
Vol 29 (6) ◽  
pp. 507-512 ◽  
Author(s):  
Yng-Tay Chen ◽  
Jiunn-Wang Liao ◽  
Dong-Zong Hung
Keyword(s):  
Alcohol Dehydrogenase ◽  
Aldehyde Dehydrogenase ◽  
Lethal Dose ◽  
Protective Role ◽  
Vital Role ◽  
Glutathione Metabolism ◽  
Toxic Metabolite ◽  
Protective Effects ◽  
Median Lethal Dose ◽  
Strong Interest

2-Chloroethanol (2-CE) is a widely used industrial solvent. In Taiwan, Taiwanese farmers apply 2-CE on grape-vines to accelerate grape growth, a practice that in some cases have caused poisoning in humans. Thus, there is strong interest in identifying antidotes to 2-CE. This study examines the protective role in 2-CE intoxicated rats. Alcohol dehydrogenase and glutathione were hypothesized to be important in the metabolism of 2-CE. This study used fomepizole, an alcohol dehydrogenase inhibitor, and chemicals that affected glutathione metabolism to study 2-CE toxicity. Notably, fomepizole 5 mg/kg significantly increased median lethal dose (LD50) of 2-CE from 65.1 to 180 mg/kg and reduced the production of a potential toxic metabolite chloroacetaldehyde (CAA) in animal plasma. In contrast, disulfiram (DSF), an aldehyde dehydrogenase inhibitor, increased the toxicity of 2-CE on the lethality in rats. Additional or pretreatment with N-acetylcysteine (NAC) and fomepizole significantly reduced plasma CAA concentrations. Fomepizole also significantly reduced 2-CEinhibited glutathione activity. Otherwise, pretreatment with NAC for 4 days followed by co-treatment with fomepizole significantly decreased formation of the metabolic CAA. These results indicated that its catalytic enzyme might play a vital role during 2-CE intoxication, and the combination of fomepizole and NAC could be a protective role in cases of acute 2-CE intoxication.

Ameliorative Effect of Natural and Synthetic Antioxidants on Arsenic Toxicity in Male Mice: Biochemical and Histological Perspectives

2018 ◽  
Author(s):  
Sayed Amer ◽  
Yousif Al-Zahrani ◽  
Mohammad AL-Harbi
Keyword(s):  
Mononuclear Cell ◽  
Lethal Dose ◽  
Treated Group ◽  
Blood Parameters ◽  
Protective Role ◽  
Cell Infiltration ◽  
Arsenic Toxicity ◽  
Protective Effects ◽  
Mononuclear Cell Infiltration ◽  
Sodium Arsenate

The present study aimed to investigate the protective effects of some natural and artificial antioxidants on the hepato-renal injuries induced by arsenic toxicity. Sixty adult male albino mice weighing 30-40 g were subjected to a sub-lethal dose of sodium arsenate (40 mg/kg body weight) to investigate hematological, biochemical and histopathological alterations resulting from arsenic-induced hepato-renal toxicity. Arsenic-exposed mice were also co-treated with different antioxidants including green tea, garlic and vitamin C to reveal their potential protective role. The antioxidants induced normalization of all blood parameters that showed significant declines by arsenic toxicity. ALT and AST activities were significantly increased in sodium arsenate treated group compared to all other groups. These enzymes did not acquire insignificant differences in antioxidants-treated groups compared to the control mice. Creatinine and urea were significantly increased in arsenate treated mice and become normal in mice co-treated with different antioxidants. Liver sections of arsenate treated mice showed venous congestion, sinusoidal dilatation, mononuclear cell infiltration and periportal fibrosis. Renal sections in the same groups revealed interstitial hemorrhages, mononuclear cell infiltration, glomerulonephritis and proximal tubular necrosis. Hepato-renal histopathology was greatly reduced, particularly, in groups received combined antioxidants. The used antioxidants, therefore, exhibited potential protection against hepato-renal induced arsenic toxicity.

Compounds from Ilex paraguariensis extracts have antioxidant effects in the brains of rats subjected to chronic immobilization stress

2017 ◽  
Vol 42 (11) ◽  
pp. 1172-1178 ◽  
Author(s):  
Ana C. Colpo ◽  
Maria Eduarda de Lima ◽  
Marisol Maya-López ◽  
Hemerson Rosa ◽  
Cristina Márquez-Curiel ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Immobilization Stress ◽  
Brain Regions ◽  
Protective Role ◽  
Ilex Paraguariensis ◽  
Protective Effects ◽  
Species Formation ◽  
Lipid And Protein Oxidation ◽  
Response To Stress ◽  
Chronic Immobilization Stress

Immobilization induces oxidative damage to the brain. Ilex paraguariensis extracts (Mate) and their major natural compound, chlorogenic acid (CGA), exert protective effects against reactive oxygen species formation. Here, the effects of Mate and CGA on oxidative damage induced by chronic immobilization stress (CIS) in the cortex, hippocampus, and striatum were investigated. For CIS, animals were immobilized for 6 h every day for 21 consecutive days. Rats received Mate or CGA by intragastric gavage 30 min before every restraint session. Endpoints of oxidative stress (levels of lipid peroxidation, protein carbonylation, and reduced (GSH) and oxidized (GSSG) forms of glutathione) were evaluated following CIS. While CIS increased oxidized lipid and carbonyl levels in all brain regions, CGA (and Mate to a lesser extent) attenuated lipid and protein oxidation as compared with control groups. GSH/GSSG balance showed a tendency to increase in all regions in response to stress and antioxidants. Taken together, our results support a protective role of dietary antioxidants against the neuronal consequences of stress.

scholarly journals Protective Effects of 6,7,4′-Trihydroxyflavanone on Hypoxia-Induced Neurotoxicity by Enhancement of HO-1 through Nrf2 Signaling Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 341 ◽  
Author(s):  
Hyun-Su Lee ◽  
Gil-Saeng Jeong
Keyword(s):  
Signaling Pathway ◽  
Neurodegenerative Disorders ◽  
Nuclear Translocation ◽  
Protoporphyrin Ix ◽  
Protective Role ◽  
Osteoclast Formation ◽  
Protective Effects ◽  
Protein Levels ◽  
Nrf2 Signaling Pathway ◽  
Pre Treatment

Since hypoxia-induced neurotoxicity is one of the major causes of neurodegenerative disorders, including the Alzheimer’s disease, continuous efforts to find a novel antioxidant from natural products are required for public health. 6,7,4′-trihydroxyflavanone (THF), isolated from Dalbergia odorifera, has been shown to inhibit osteoclast formation and have an antibacterial activity. However, no evidence has reported whether THF has a protective role against hypoxia-induced neurotoxicity. In this study, we found that THF is not cytotoxic, but pre-treatment with THF has a cytoprotective effect on CoCl2-induced hypoxia by restoring the expression of anti-apoptotic proteins in SH-SY5y cells. In addition, pre-treatment with THF suppressed CoCl2-induced hypoxia-related genes including HIF1α, p53, VEGF, and GLUT1 at the mRNA and protein levels. Pre-treatment with THF also attenuated the oxidative stress occurred by CoCl2-induced hypoxia by preserving antioxidant proteins, including SOD and CAT. We revealed that treatment with THF promotes HO-1 expression through Nrf2 nuclear translocation. An inhibitor assay using tin protoporphyrin IX (SnPP) confirmed that the enhancement of HO-1 by pre-treatment with THF protects SH-SY5y cells from CoCl2-induced neurotoxicity under hypoxic conditions. Our results demonstrate the advantageous effects of THF against hypoxia-induced neurotoxicity through the HO-1/Nrf2 signaling pathway and provide a therapeutic insight for neurodegenerative disorders.

scholarly journals Protective Effects of Statins Administration in European and North American Patients Infected with COVID-19: A Meta-analysis

2021 ◽  
Author(s):  
Mairi Pucci ◽  
Diletta Onorato ◽  
Giovanni Carpene ◽  
Brandon Michael Henry ◽  
Fabian Sanchis-Gomar ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Statin Therapy ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Protective Role ◽  
Favorable Effect ◽  
Current Evidence ◽  
Severe Illness ◽  
Protective Effects ◽  
Time Data

AbstractSevere acute respiratory syndrome coronavirus 2 has spread rapidly throughout the world, becoming an overwhelming global health emergency. The array of injuries caused by this virus is broad and not limited to the respiratory system, but encompassing also extensive endothelial and systemic tissue damage. Since statins effectively improve endothelial function, these drugs may have beneficial effects in patients with coronavirus disease 2019 (COVID-19). Therefore, this investigation aimed to provide an updated overview on the interplay between statins and COVID-19, with particular focus on their potentially protective role against progression toward severe or critical illness and death. A systematic electronic search was performed in Scopus and PubMed up to present time. Data on statins use and COVID-19 outcomes especially in studies performed in Europe and North America were extracted and pooled. A total of seven studies met our inclusion criteria, totaling 2,398 patients (1,075 taking statins, i.e., 44.8%). Overall, statin usage in Western patients hospitalized with COVID-19 was associated with nearly 40% lower odds of progressing toward severe illness or death (odds ratio: 0.59; 95% confidence interval: 0.35–0.99). After excluding studies in which statin therapy was started during hospital admission, the beneficial effect of these drugs was magnified (odds ratio: 0.51; 95% confidence interval: 0.41–0.64). In conclusion, although randomized trials would be necessary to confirm these preliminary findings, current evidence would support a favorable effect of statins as adjuvant therapy in patients with COVID-19. Irrespective of these considerations, suspension of statin therapy seems highly unadvisable in COVID-19 patients.

Anti-inflammatory and prolonged protective effects of Artemisia herba-alba extracts via glutathione metabolism reinforcement

2021 ◽  
Vol 142 ◽  
pp. 206-215
Author(s):  
Nadjet Bouchara ◽  
François Senejoux ◽  
Didier Fraisse ◽  
Catherine Felgines ◽  
Florence Caldéfie-Chezet ◽  
...  
Keyword(s):  
Glutathione Metabolism ◽  
Protective Effects ◽  
Anti Inflammatory

scholarly journals Prostaglandin E2Receptor Antagonist with Antimicrobial Activity against Methicillin-ResistantStaphylococcus aureus

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Mélanie A. C. Ikeh ◽  
Paul L. Fidel ◽  
Mairi C. Noverr
Keyword(s):  
Antimicrobial Activity ◽  
Receptor Antagonist ◽  
Enzyme Inhibitors ◽  
Lethal Dose ◽  
Prostaglandin E ◽  
Protective Effects ◽  
Physiological Concentration ◽  
Content Type ◽  
Abdominal Infections

ABSTRACTPolymicrobial intra-abdominal infections (IAI) involvingCandida albicansandStaphylococcus aureusare associated with severe morbidity and mortality (∼80%). Our laboratory discovered that the immunomodulatory eicosanoid prostaglandin E2(PGE2) plays a key role in the lethal inflammatory response during polymicrobial IAI using a mouse model of infection. In studies designed to uncover key PGE2biosynthesis/signaling components involved in the response, selective eicosanoid enzyme inhibitors and receptor antagonists were selected and prescreened for antimicrobial activity againstC. albicansorS. aureus. Unexpectedly, we found that the EP4receptor antagonist L-161,982 had direct growth-inhibitory effects onS. aureusin vitroat the physiological concentration required to block the PGE2interaction with EP4. This antimicrobial activity was observed with methicillin-sensitiveS. aureusand methicillin-resistantS. aureus(MRSA) strains, with the MIC and minimum bactericidal concentration values for planktonic cells being 50 μg/ml and 100 μg/ml, respectively. In addition, L-161,982 inhibitedS. aureusbiofilm formation and had activity against preformed mature biofilms. More importantly, treatment of mice with L-161,982 following intraperitoneal inoculation with a lethal dose of MRSA significantly reduced the bioburden and enhanced survival. Furthermore, L-161,982 protected mice against the synergistic lethality induced by coinfection withC. albicansandS. aureus. The antimicrobial activity of L-161,982 is independent of EP4receptor inhibitory activity; an alternative EP4receptor antagonist exerted no antimicrobial or protective effects. Taken together, these findings demonstrate that L-161,982 has potent antimicrobial activity against MRSA and may represent a significant therapeutic alternative in improving the prognosis of mono- or polymicrobial infections involving MRSA.

scholarly journals N-Acetylcysteine Reduces the Pro-Oxidant and Inflammatory Responses during Pancreatitis and Pancreas Tumorigenesis

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1107
Author(s):  
Marie-Albane Minati ◽  
Maxime Libert ◽  
Hajar Dahou ◽  
Patrick Jacquemin ◽  
Mohamad Assi
Keyword(s):  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Glutathione Metabolism ◽  
Protective Effects ◽  
Wild Type ◽  
Kras Mutations ◽  
Oxidative Damages ◽  
Factor Α

Pancreatitis, an inflammation of the pancreas, appears to be a main driver of pancreatic cancer when combined with Kras mutations. In this context, the exact redox mechanisms are not clearly elucidated. Herein, we treated mice expressing a KrasG12D mutation in pancreatic acinar cells with cerulein to induce acute pancreatitis. In the presence of KrasG12D, pancreatitis triggered significantly greater redox unbalance and oxidative damages compared to control mice expressing wild-type Kras alleles. Further analyses identified the disruption in glutathione metabolism as the main redox event occurring during pancreatitis. Compared to the wild-type background, KrasG12D-bearing mice showed a greater responsiveness to treatment with a thiol-containing compound, N-acetylcysteine (NAC). Notably, NAC treatment increased the pancreatic glutathione pool, reduced systemic markers related to pancreatic and liver damages, limited the extent of pancreatic edema and fibrosis as well as reduced systemic and pancreatic oxidative damages. The protective effects of NAC were, at least, partly due to a decrease in the production of tumor necrosis factor-α (TNF-α) by acinar cells, which was concomitant with the inhibition of NF-κB(p65) nuclear translocation. Our data provide a rationale to use thiol-containing compounds as an adjuvant therapy to alleviate the severity of inflammation during pancreatitis and pancreatic tumorigenesis.

ROBUST ESTIMATION OF THE MEDIAN LETHAL DOSE

2002 ◽  
Vol 12 (2) ◽  
pp. 137-147 ◽  
Author(s):  
G. E. Kelly ◽  
J. K. Lindsey
Keyword(s):  
Robust Estimation ◽  
Lethal Dose ◽  
Median Lethal Dose

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

2009 ◽  
Vol 25 (3) ◽  
pp. 183-188 ◽  
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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