Arnold N. Onyango

New hypotheses on the pathways of formation of malondialdehyde and isofurans

Malondialdehyde (MDA) is a mutagenic compound that has been widely used as a biomarker of oxidative stress. However, the nonenzymatic mechanisms of its formation are not well understood. Some lipid oxidation products were previously suggested to be MDA precursors and found to afford MDA heterolytically under acidic conditions. We predict that some of these compounds are not important MDA sources under the autoxidative conditions under which the bulk of MDA should be formed in vivo and that others require further oxidative modifications to generate MDA homolytically. Thus, we outline the likely important pathways of MDA formation in vivo. All these pathways are intense aldehyde producers, generating two other aldehydic products for every MDA molecule formed. Some of the predicted aldehydes are new and may merit further analytical and biological studies. Peracids derived from the aldehydes are proposed to participate in the formation of isofurans (which at high oxygen tensions are excellent markers of oxidative stress) as well as important bioactive epoxides such as leukotoxins. This generates interest in the biological relevance of lipid aldehyde-derived peracids. The suitability of tissue MDA determination methods is discussed based on their likelihood of involving acid-catalyzed artifactual MDA formation.

Small reactive carbonyl compounds as tissue lipid oxidation products; and the mechanisms of their formation thereby

Small reactive carbonyl compounds (RCCs) such as formaldehyde, acetaldehyde, acrolein, crotonaldehyde, glyoxal, methylglyoxal, glycolaldehyde, glycidaldehyde, and 2-butene-1,4-dial are involved in carbonyl and oxidative stress-related physiological disorders. While some evidence indicates that lipid oxidation could be an important source of these compounds in vivo, this has sometimes been doubted because the mechanisms of their formation thereby are poorly understood. Here, representative literature supporting the significant formation of these compounds during lipid oxidation under physiologically relevant conditions are highlighted, and the strengths and weaknesses of previously proposed mechanisms of their formation thereby are considered. In addition, based on the current understanding of lipid oxidation chemistry, some new pathways of their formation are suggested. The suggested pathways also generate 4-hydroxy-2-butenal, a precursor of the carcinogen furan, whose endogenous formation in tissues has hitherto not been seriously considered.

Endogenous Generation of Singlet Oxygen and Ozone in Human and Animal Tissues: Mechanisms, Biological Significance, and Influence of Dietary Components

Recent studies have shown that exposing antibodies or amino acids to singlet oxygen results in the formation of ozone (or an ozone-like oxidant) and hydrogen peroxide and that human neutrophils produce both singlet oxygen and ozone during bacterial killing. There is also mounting evidence that endogenous singlet oxygen production may be a common occurrence in cells through various mechanisms. Thus, the ozone-producing combination of singlet oxygen and amino acids might be a common cellular occurrence. This paper reviews the potential pathways of formation of singlet oxygen and ozone in vivo and also proposes some new pathways for singlet oxygen formation. Physiological consequences of the endogenous formation of these oxidants in human tissues are discussed, as well as examples of how dietary factors may promote or inhibit their generation and activity.

Different behavior of artemisinin and tetraoxane in the oxidative degradation of phospholipid

The reaction of trioxane and tetraoxane endoperoxides with unsaturated phospholipid 1 in the presence of Fe(II) was investigated in the absence of oxygen by means of tandem ESI-MS analysis. The spectral analyses for the reaction mixtures showed that artemisinin 2 with a trioxane structure gave no peak except that for the remaining intact phospholipid 1 (m/z 758.9), indicating that there was no structural change to 1. On other hand, the reaction mixture of 1 with tetraoxanes 3 and 4 afforded a number of new peaks (m/z 620-850) that were presumably assigned to oxidative degradation products originating from phospholipid 1. Since this reaction was completely inhibited by the addition of a phenolic antioxidant, the process was considered to involve some free radical species. The newly discovered marked differences in reactivity between the trioxane and the tetraoxanes possibly reflects their different anti-malarial mechanisms, and this reactivity may contribute to the classification of a number of anti-malarial endoperoxides whose mode of action is based on phospholipid oxidation.

Synthesis of Phospholipids Bearing a Conjugated Oxo-polyunsaturated Fatty Acid Residue

2-(15′-Oxo-5′,8′,11′,13′-eicosatetraenoyl)-1-stearoyl-sn-glycerol(3)phosphocholine (APC-CO) 1 and 2 and 2-(13′-oxo-9′,11′-octadecadienoyl)-1-stearoyl-sn-glycero(3)phosphocholine (LPC-CO) 3 are synthesized and an analytical system established for the determination of geometrical isomers at the 13′ position of APC-CO.

Harnessing microbiome and probiotic research in sub-Saharan Africa: recommendations from an African workshop

To augment capacity-building for microbiome and probiotic research in Africa, a workshop was held in Nairobi, Kenya, at which researchers discussed human, animal, insect, and agricultural microbiome and probiotics/prebiotics topics. Five recommendations were made to promote future basic and translational research that benefits Africans.

Carotenoid profiling of the leaves of selected African eggplant accessions subjected to drought stress

Abstract African eggplants (Solanum aethiopicum and S. macrocarpon) are among the most economically important and valuable vegetable and fruit crops. They are a major source of biologically active nutritional substances and metabolites which are essential for plant growth, development, stress adaptation and defense. Among these metabolites are the carotenoids which act as accessory pigments for photosynthesis and precursor to plant hormones. Though African eggplants are known to be resistant to various abiotic stresses, the effect of these stresses on secondary metabolites has not been well defined. The objective of this study was to establish the effect of drought stress on carotenoid profiles of nineteen African eggplant accessions selected based on leaf and fruit morphological traits. Stress was achieved by limiting irrigation and maintaining the wilting state of the crops. Fresh leaves were sampled at different maturity stages; before stress, 2 weeks and 4 weeks after stress for carotenoid analysis. The fresh harvested leaf tissues were immediately frozen in liquid nitrogen and ground. Analysis was carried out using a Dionex HPLC machine coupled to Photo Array Detector and Chromeleon software package (Thermo Fisher Scientific Inc, Waltham, Massachusetts, USA). Major carotenoids viz;. Xanthophylls (neoxanthin, violaxanthin, zeaxanthin and lutein) and carotenes (β–carotene and α–carotene), phytofluene, lycopene, phytoene as well as chlorophylls (chlorophyll‐b and Chlorophyll‐a) were targeted. The carotenoids increased with maturity stage of the crop. Although the stressed crops reported significantly decreased amount of carotenes, chlorophylls, neoxanthin and violaxanthin, the concentration of zeaxanthin increased with stress whereas lutein had no significant change. Chlorophyll‐a was significantly high in all the control accessions. Two accessions reported significantly higher contents of carotenoids as compared to the other accessions. The results of this study indicate that water stress has significant impact on the concentration of some carotenoids and photosynthetic pigments. This will definitely add value to the study of stress tolerance in crops.

Alternatives to the 'water oxidation pathway' of biological ozone formation.

Recent studies have shown that ozone (O3) is endogenously generated in living tissues, where it makes both positive and negative physiological contributions. A pathway for the formation of both O3 and hydrogen peroxide (H2O2) was previously proposed, beginning with the antibody or amino acid-catalyzed oxidation of water by singlet oxygen (1O2) to form hydrogen trioxide (H2O3) as a key intermediate. A key pillar of this hypothesis is that some of the H2O2 molecules incorporate water-derived oxygen atoms. However, H2O3 decomposes extremely readily in water to form 1O2 and water, rather than O3 and H2O2. This article highlights key literature indicating that the oxidation of organic molecules such as the amino acids methionine, tryptophan, histidine, and cysteine by 1O2 is involved in ozone formation. Based on this, an alternative hypothesis for ozone formation is developed involving a further reaction of singlet oxygen with various oxidized organic intermediates. H2O2 having water-derived oxygen atoms is subsequently formed during ozone decomposition in water by known reactions.

The Contribution of Singlet Oxygen to Insulin Resistance

Insulin resistance contributes to the development of diabetes and cardiovascular dysfunctions. Recent studies showed that elevated singlet oxygen-mediated lipid peroxidation precedes and predicts diet-induced insulin resistance (IR), and neutrophils were suggested to be responsible for such singlet oxygen production. This review highlights literature suggesting that insulin-responsive cells such as endothelial cells, hepatocytes, adipocytes, and myocytes also produce singlet oxygen, which contributes to insulin resistance, for example, by generating bioactive aldehydes, inducing endoplasmic reticulum (ER) stress, and modifying mitochondrial DNA. In these cells, nutrient overload leads to the activation of Toll-like receptor 4 and other receptors, leading to the production of both peroxynitrite and hydrogen peroxide, which react to produce singlet oxygen. Cytochrome P450 2E1 and cytochrome c also contribute to singlet oxygen formation in the ER and mitochondria, respectively. Endothelial cell-derived singlet oxygen is suggested to mediate the formation of oxidized low-density lipoprotein which perpetuates IR, partly through neutrophil recruitment to adipose tissue. New singlet oxygen-involving pathways for the formation of IR-inducing bioactive aldehydes such as 4-hydroperoxy-(or hydroxy or oxo)-2-nonenal, malondialdehyde, and cholesterol secosterol A are proposed. Strategies against IR should target the singlet oxygen-producing pathways, singlet oxygen quenching, and singlet oxygen-induced cellular responses.

A non-radical mechanism for the rearrangement of linoleic acid dihydroperoxides

A non-radical mechanism for the rearrangement of the 10,13-dihydroperoxide of linoleic acid to the 8,13-dihydroperoxide is proposed, and different pathways for the formation of 4-hydroperoxy-2-nonenalvia a dioxetanyl radical are speculated (the mechanism of formation of 4-hydroperoxy-2-nonenal is of great interest since it is a precursor of the highly bioactive 4-hydroxy-2-nonenal and 4-oxo-2-nonenal).