Active involvement of catalase during hemolytic crises of favism

Abstract

The endemic occurrence of favism in certain Mediterranean regions provided an investigative opportunity for testing in vivo the validity of claims as to the role of catalase in protecting human erythrocytes against peroxidative injury. Reduced activity of catalase was found in the erythrocytes of six boys who were deficient in erythrocytic glucose- 6-phosphate dehydrogenase (G6PD) and who were studied while suffering hemolysis after ingesting fava beans. Activity of catalase was further reduced when their red blood cells were incubated with aminotriazole. In contrast, minimal reduction of catalase activity was found, both with and without incubation with aminotriazole, in erythrocytes of a G6PD-deficient boy who had ingested fava beans 7 days earlier and in erythrocytes of seven G6PD-deficient men with a past history of favism. These results confirmed earlier studies in vitro indicating that catalase is a major disposer of hydrogen peroxide in human erythrocytes and, like the glutathione peroxidase/reductase pathway, is dependent on the availability of reduced nicotinamide adenine dinucleotide phosphate (NADPH). The effect of divicine on purified catalase and on the catalase of intact G6PD-deficient erythrocytes was similar to the previously demonstrated effect on catalase of a known system for generating hydrogen peroxide. This effect of divicine strengthens earlier arguments that divicine is the toxic peroxidative component of fava beans.

G6PD deficiency: a classic example of pharmacogenetics with on‐going clinical implications

“…First, with other drugs the precise chemical mechanism whereby they cause oxidative damage is not fully understood: for rasburicase – a genetically engineered form of the enzyme urate oxidase – we know instead that, like all other oxidases, one of the products of the enzyme reaction is hydrogen peroxide, of which one molecule is produced stoichiometrically for every molecule of uric acid that is catabolized. In normal cells, hydrogen peroxide is promptly degraded by either glutathione peroxidase (GSHPX) or catalase, but in red cells of G6PD-deficient subjects, GSHPX activity is impaired because GSH is in short supply (Fig 4 ), and catalase may also be impaired because the intracellular NADPH concentration is low (Gaetani et al , 1994 , 1996 ). Second, presumably as a result of this mechanism, in G6PD-deficient subjects rasburicase causes both AHA and acute methaemoglobinaemia – the latter can reach levels of up to 20%, much higher than that seen with other drugs.…”

Embryonic catalase protects against endogenous and phenytoin‐enhanced DNA oxidation and embryopathies in acatalasemic and human catalase‐expressing mice

“…Numerous studies have demonstrated a protective role for exogenous forms of catalase against reactive oxygen species (ROS)-mediated damage, including ischemic-reperfusion injury (5)(6)(7), cold injury (8), and favism (9). A potential protective role for embryonic catalase has been suggested by studies in murine embryo culture, where the addition of exogenous catalase enhanced embryonic antioxidative activity and protected against DNA oxidation and embryopathies initiated by the ROS-initiating antiepileptic drug sodium diphenylhydantoin (phenytoin; ref.…”

Predicting the Kinetic Properties Associated with Redox Imbalance after Oxidative Crisis in G6PD-Deficient Erythrocytes: A Simulation Study

“…The increase in CAT and GSHpx activity in conditions where oxidative stress is sufficiently increased has also been shown in experimental data [ 34 , 36 ]. Furthermore, CAT has been recognized to have a predominant role in the removal of ROS [ 37 ], which explains the relatively high activation of CAT seen in our simulation results. Although oxidative stress-induced changes were present in the levels of all metabolites and antioxidant enzyme activity, initial levels were restored shortly after the perturbation, supporting previous observations implying that RBC metabolism is not dramatically affected by the deficiency of G6PD enzyme activity [ 38 ].…”