Peroxidases: a role in the metabolism and side effects of drugs

Tafazoli, Shahrzad; O’Brien, Peter J.

doi:10.1016/s1359-6446(05)03394-5

Cited by 72 publications

(28 citation statements)

References 69 publications

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“…Antioxidant enzymes, including SOD and CAT, may either directly detoxify the ROS produced or facilitate antioxidant reactions using GSH as a reducing agent (26). CAT is responsible for the decomposition of peroxides in a cell (27). In the present study, disturbances in the balance between the ROS levels and expression of antioxidant defenses were indicated and LUT was revealed to efficiently resolve this imbalance.…”

Section: Discussionmentioning

confidence: 63%

Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of liver cancer

2016

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Abstract. Liver cancer is one of the leading causes of cancer-associated mortality worldwide. Due to changes in lifestyle and daily exposure to various chemicals, which may lead to chemical intoxication, liver cancer has become a prominent disease in humans. Chemical-induced carcinogenesis in experimental animals has become a reliable model for the investigation of liver cancer-associated biological alterations that may mimic human hepatic cancer. Liver cancer in BALB/c mice was induced by administering diethylnitrosamine (DN) in drinking water for 6 weeks. Luteolin (LUT) is a flavone that is found in the leaves of the majority of spice-associated plants. In the present study, 20 µg/kg of body weight LUT was administered intraperitoneally every alternate day to treat the DN-induced liver cancer in mice. LUT improved the host system by modifying the levels of α-fetoprotein, enzymatic antioxidants, such as superoxide dismutase and catalase, marker enzymes, such as AST and ALT, and lipid peroxides in the plasma or liver tissue. LUT also reduced the levels of glutathione and the inflammatory cytokines interleukin-2 and interferon-γ in the plasma or liver tissue. These findings augmented the treatment against liver cancer and supported the effective anticancer activity of LUT against DN-induced liver carcinogenesis in mice.

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Section: Discussionmentioning

confidence: 63%

Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of liver cancer

2016

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“…It is possibly most important within phagosomes during bacterial killing because superoxide is continuously available to the enzyme. It is also likely to be involved in drug metabolism because a wide variety of drugs interact with neutrophils to promote adverse effects (50,51).…”

Section: Discussionmentioning

confidence: 99%

Superoxide-dependent Oxidation of Melatonin by Myeloperoxidase

Ximenes

Silva

Rodrigues

et al. 2005

Journal of Biological Chemistry

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Myeloperoxidase uses hydrogen peroxide to oxidize numerous substrates to hypohalous acids or reactive free radicals. Here we show that neutrophils oxidize melatonin to N 1 -acetyl-N 2 -formyl-5-methoxykynuramine (AFMK) in a reaction that is catalyzed by myeloperoxidase. Production of AFMK was highly dependent on superoxide but not hydrogen peroxide. It did not require hypochlorous acid, singlet oxygen, or hydroxyl radical. Purified myeloperoxidase and a superoxide-generating system oxidized melatonin to AFMK and a dimer. The dimer would result from coupling of melatonin radicals. Oxidation of melatonin was partially inhibited by catalase or superoxide dismutase. Formation of AFMK was almost completely eliminated by superoxide dismutase but weakly inhibited by catalase. In contrast, production of melatonin dimer was enhanced by superoxide dismutase and blocked by catalase. We propose that myeloperoxidase uses superoxide to oxidize melatonin by two distinct pathways. One pathway involves the classical peroxidation mechanism in which hydrogen peroxide is used to oxidize melatonin to radicals. Superoxide adds to these radicals to form an unstable peroxide that decays to AFMK. In the other pathway, myeloperoxidase uses superoxide to insert dioxygen into melatonin to form AFMK. This novel activity expands the types of oxidative reactions myeloperoxidase can catalyze. It should be relevant to the way neutrophils use superoxide to kill bacteria and how they metabolize xenobiotics.Catalysis of hypochlorous acid production is the accepted physiological function of myeloperoxidase (MPO) 2 (1, 2). This heme enzyme is the major protein in neutrophils and is also present in monocytes, macrophages, microglia (3), and neurons (4, 5). It reacts with hydrogen peroxide to form the redox intermediate compound I, which oxidizes chloride to hypochlorous acid with coincident regeneration of the native enzyme (Reactions 1 and 2). HOCl indicates hypochlorous acid.Myeloperoxidase also promotes the oxidation of numerous substrates (RH) to free radical intermediates via the classical peroxidase cycle involving compound I and compound II (Reactions 3 and 4).Klebanoff (6) was the first to show that myeloperoxidase has potent antimicrobial activity because of its ability to generate hypochlorous acid. He proposed that myeloperoxidase produces hypochlorous acid inside phagosomes where it reacts with and kills ingested bacteria. However, during microbial killing myeloperoxidase functions in the presence of a high flux of superoxide (7). Superoxide reacts rapidly with native enzyme to produce oxymyeloperoxidase or compound III (Reaction 5; k 5 ϭ 2 ϫ 10 6 M Ϫ1 s Ϫ1 (8)), which is the dominant form of myeloperoxidase in stimulated neutrophils (9). Reactions of superoxide with myeloperoxidase are likely to be important in host defense because it has been demonstrated that superoxide enhances myeloperoxidasedependent killing of Staphylococcus aureus by isolated human neutrophils (10). The nature of this interaction has yet to be revealed.Compound II...

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“…(135,136) A number of drugs and xenobiotics induce adverse biological effects, including agranulocytosis, hepatotoxicity and cancer, which have been associated with their metabolism by heme peroxidases. (136,137) …”

Section: Reactions Of Hypohalous Acidsmentioning

confidence: 99%

Myeloperoxidase-derived oxidation: mechanisms of biological damage and its prevention

Davies

2010

J. Clin. Biochem. Nutr.

346

228

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There is considerable interest in the role that mammalian heme peroxidase enzymes, primarily myeloperoxidase, eosinophil peroxidase and lactoperoxidase, may play in a wide range of human pathologies. This has been sparked by rapid developments in our understanding of the basic biochemistry of these enzymes, a greater understanding of the basic chemistry and biochemistry of the oxidants formed by these species, the development of biomarkers that can be used damage induced by these oxidants in vivo, and the recent identification of a number of compounds that show promise as inhibitors of these enzymes. Such compounds offer the possibility of modulating damage in a number of human pathologies. This reviews recent developments in our understanding of the biochemistry of myeloperoxidase, the oxidants that this enzyme generates, and the use of inhibitors to inhibit such damage.

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Peroxidases: a role in the metabolism and side effects of drugs

Cited by 72 publications

References 69 publications

Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of liver cancer

Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of liver cancer

Superoxide-dependent Oxidation of Melatonin by Myeloperoxidase

Myeloperoxidase-derived oxidation: mechanisms of biological damage and its prevention

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