Toxicity of glyoxals – role of oxidative stress, metabolic detoxification and thiamine deficiency

2003 ◽  
Vol 31 (6) ◽  
pp. 1390-1393 ◽  
Author(s):  
N. Shangari ◽  
W.R. Bruce ◽  
R. Poon ◽  
P.J. O'Brien

Glyoxals are reactive α-oxoaldehydes that are formed endogenously from sugars, the levels of which are increased in various pathological conditions associated with hyperglycaemia and thiamine deficiency. However, the molecular cytotoxic mechanisms of glyoxal are not known. Results presented here and in the other studies cited provide a glimpse into the cytotoxicity mechanisms involved and their pathological implications. We found that glyoxal (10 μM) markedly increased the susceptibility of hepatocyte glutathione (GSH) to oxidation by hydrogen peroxide (H2O2) and markedly increased cytotoxicity by compromising the cellular antioxidant enzyme system. At higher concentrations, glyoxal was cytotoxic towards hepatocytes, which can be attributed to GSH depletion, oxidative stress and mitochondrial toxicity. Aminoguanidine or penicillamine protected the hepatocytes. Glyoxal cytotoxicity was prevented by increasing glyoxal metabolism with thiamine or NAD(P)H generators, and was increased in GSH- or thiamine-deficient hepatocytes. It was also found that feeding rats reduced thiamine levels in a diet high in simple sugars increased the number of aberrant crypt foci/colon in the absence of clinical evidence of beriberi. This was associated with decreased plasma thiamine and low erythrocyte transketolase activity. Western diets, which are frequently poor in thiamine and high in sugars, could result in increased levels of endogenous glyoxals, which in turn may lead to a predisposition to AGE (advanced glycation end-product)-related pathologies and neoplastic conditions.

2010 ◽  
Vol 56 (10) ◽  
pp. 816-821 ◽  
Author(s):  
Snowber Yousuf ◽  
Aijaz Ahmad ◽  
Amber Khan ◽  
Nikhat Manzoor ◽  
Luqman Ahmad Khan

This study was carried out to show the effect of diallyldisulphide (DADS), an important organosulphur compound found in garlic ( Allium sativum ), on antioxidant systems in Candida species. Changes in antioxidant metabolites and antioxidant activity in the presence of DADS were found in Candida albicans and Candida tropicalis . Candida cells were treated with sublethal concentrations of DADS. DADS caused a decrease in the activity of all antioxidant enzymes except catalase, resulting in oxidative stress and damaged cells. The amount of oxidative stress generated by DADS was found to be a function of its concentration. A significant decrease in superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase activities but an increase in catalase activity were observed. Increased levels of lipid peroxidation and decreased levels of glutathione were observed in treated cells. Activity of glucose-6-phosphate dehydrogenase decreased significantly following DADS treatment and could be correlated with a decrease in glutathione concentration in both Candida species. These results indicate that diallyl disulphide acts as a pro-oxidant to Candida species and hence may act as a potent antifungal in the management of candidiasis.


2009 ◽  
Vol 11 (3) ◽  
pp. 281-295 ◽  

Astrocytes are the main neural cell type responsible for the maintenance of brain homeostasis. They form highly organized anatomical domains that are interconnected into extensive networks. These features, along with the expression of a wide array of receptors, transporters, and ion channels, ideally position them to sense and dynamically modulate neuronal activity. Astrocytes cooperate with neurons on several levels, including neurotransmitter trafficking and recycling, ion homeostasis, energy metabolism, and defense against oxidative stress. The critical dependence of neurons upon their constant support confers astrocytes with intrinsic neuroprotective properties which are discussed here. Conversely, pathogenic stimuli may disturb astrocytic function, thus compromising neuronal functionality and viability. Using neuroinflammation, Alzheimer's disease, and hepatic encephalopathy as examples, we discuss how astrocytic defense mechanisms may be overwhelmed in pathological conditions, contributing to disease progression.


2021 ◽  
Vol 17 ◽  
Author(s):  
Joseph A. Adeyemi ◽  
Victor O. Ukwenya ◽  
Olatunbosun K. Arowolo ◽  
Christian C. Olise

: Increased applications of pesticides mainly in agriculture and public health has resulted in increased chances of human exposure to pesticides. Chronic exposure to pesticides has been implicated in several human diseases including cardiovascular diseases. Cardiovascular diseases are broadly used for various heart pathological conditions including defect blood vessels, and they include myocardial infarction, atherosclerosis, stroke, cardiomyopathy, coronary heart disease etc. In this review, the association between human exposure to pesticides and development of cardiovascular diseases was discussed using epidemiological and laboratory data. The toxicokinetics of pesticides in humans was reviewed, as well as the risk factors for cardiovascular diseases. The important role of oxidative stress, and principally the induction of reactive oxygen species as the signaling molecules for various signaling pathways involved in pesticidesinduced cardiovascular disease was discussed.


2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Min Hee Choi ◽  
Jin Rong Ow ◽  
Nai-Di Yang ◽  
Reshma Taneja

Oxidative stress is a loss of balance between the production of reactive oxygen species during cellular metabolism and the mechanisms that clear these species to maintain cellular redox homeostasis. Increased oxidative stress has been associated with muscular dystrophy, and many studies have proposed mechanisms that bridge these two pathological conditions at the molecular level. In this review, the evidence indicating a causal role of oxidative stress in the pathogenesis of various muscular dystrophies is revisited. In particular, the mediation of cellular redox status in dystrophic muscle by NF-κB pathway, autophagy, telomere shortening, and epigenetic regulation are discussed. Lastly, the current stance of targeting these pathways using antioxidant therapies in preclinical and clinical trials is examined.


2020 ◽  
Vol 11 ◽  
Author(s):  
Jun Song ◽  
Leslie CampbellPalmer ◽  
Mindy Vinqvist-Tymchuk ◽  
Sherry Fillmore ◽  
Charles Forney ◽  
...  

To investigate the strawberry antioxidant defense system during fruit ripening, a targeted quantitative proteomic approach using multiple reaction monitoring (MRM) was developed to investigate targeted proteins in the antioxidant enzyme system in strawberry fruit. We investigated 46 proteins and isoforms with 73 identified peptides which may be involved in this antioxidant enzyme system. Among the proteins that changed during ripening, aldo/keto reductase (AKR), superoxide dismutase (SOD) and glutathione transferase (GT) increased significantly, while dehydroascorbate reductase, 2-Cys peroxiredoxin, catalase (CAT), 1-Cys peroxiredoxin and L-ascorbate peroxidase (APX) decreased significantly. These results suggest that fruit ripening of strawberry activates the enzymes of an SOD/glutathione metabolism system. The methodologies used in this study will be useful for systematically characterizing the role of antioxidant enzymes in fruit ripening of other plants.


Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 105
Author(s):  
Francesco Sabbatino ◽  
Valeria Conti ◽  
Luigi Liguori ◽  
Giovanna Polcaro ◽  
Graziamaria Corbi ◽  
...  

Reactive oxygen species (ROS) are molecules involved in signal transduction pathways with both beneficial and detrimental effects on human cells. ROS are generated by many cellular processes including mitochondrial respiration, metabolism and enzymatic activities. In physiological conditions, ROS levels are well-balanced by antioxidative detoxification systems. In contrast, in pathological conditions such as cardiovascular, neurological and cancer diseases, ROS production exceeds the antioxidative detoxification capacity of cells, leading to cellular damages and death. In this review, we will first describe the biology and mechanisms of ROS mediated oxidative stress in cardiovascular disease. Second, we will review the role of oxidative stress mediated by oncological treatments in inducing cardiovascular disease. Lastly, we will discuss the strategies that potentially counteract the oxidative stress in order to fight the onset and progression of cardiovascular disease, including that induced by oncological treatments.


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