Differences in glyoxal and methylglyoxal metabolism determine cellular susceptibility to protein carbonylation and cytotoxicity

Protective effects of ferulic acid and related polyphenols against glyoxal- or methylglyoxal-induced cytotoxicity and oxidative stress in isolated rat hepatocytes

“…GO or MGO increased cytotoxicity, ROS formation, DNA oxidation, protein carbonylation, and decreased mitochondrial membrane potential (MMP) in a concentration and time dependent manner in isolated rat hepatocytes [1,3,8]. Glyoxalase I was found to be the main detoxification enzyme for MGO while it played a very minor role in detoxifying GO [12].…”

“…Moreover, GO and MGO can also be metabolized by aldehyde dehydrogenase (ALDH2). GO metabolism relied on ALDH2 whereas glyoxalase I played a more important role than ALDH2 in MGO's detoxification [3,13,14]. Additional hydrogen peroxide (H 2 O 2 ) from either endogenous catalase inhibition or from an exogenous source such as glucose/glucose oxidase (a non-toxic H 2 O 2 generating system) increased GO formation from glycolaldehyde and also promoted radical formation from GO and possibly from MGO [3].…”

“…GO metabolism relied on ALDH2 whereas glyoxalase I played a more important role than ALDH2 in MGO's detoxification [3,13,14]. Additional hydrogen peroxide (H 2 O 2 ) from either endogenous catalase inhibition or from an exogenous source such as glucose/glucose oxidase (a non-toxic H 2 O 2 generating system) increased GO formation from glycolaldehyde and also promoted radical formation from GO and possibly from MGO [3]. Our laboratory previously demonstrated that fructose-induced hepatotoxicity increased more than 100-fold in the presence of a non-toxic concentration of H 2 O 2 so as to mimic H 2 O 2 levels formed by NADPH oxidase (NOX) released by activated immune cells such as neutrophils, eosinophils, and macrophages during an acute episode of inflammation [15,16].…”

“…These reactive dicarbonyls (GO and MGO) can be formed through the oxidation of commonly used reducing sugars e.g., fructose under chronic hyperglycemic conditions. Moreover, endogenous MGO can also be formed from the triose phosphate intermediates of glycolysis [3,4]. Abnormal glucose metabolism often leads to glucose intolerance and hyperglycemia in diabetes mellitus patients.…”

The Postulated Hepatotoxic Metabolite of Methimazole Causes Mitochondrial Dysfunction and Energy Metabolism Disturbances in Liver

“…14,16,40 Glyoxal is a well-known mitochondrial toxin. [43][44][45] It has been reported that a part of methimazole hepatotoxicity might be mediated by glyoxal. 46 Hence, methimazole metabolites might synergistically disturb hepatocytes mitochondrial function (Figure 7).…”