Interaction of Antimycobacterial Drugs with the Anti-<i>Mycobacterium avium</i>Complex Effects of Antimicrobial Effectors, Reactive Oxygen Intermediates, Reactive Nitrogen Intermediates, and Free Fatty Acids Produced by Macrophages

Sano, Keisuke; Tomioka, Haruaki; Sato, Katsumasa; Sano, Chiaki; Kawauchi, Hideyuki; Cai, Shanshan; Shimizu, Toshiaki

doi:10.1128/aac.48.6.2132-2139.2004

Cited by 10 publications

(5 citation statements)

References 35 publications

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“…Resident macrophages have some capacity to undergo a respiratory burst, but immunologic activation of macrophages substantially augments this process [ 14 ]. The antimicrobial activity of ROIs has been demonstrated by a variety of approaches and has been most strongly implicated in host defenses against intracellular pathogens such as Listeria monocytogenes , Mycobacterium avium and Francisella tularensis [ 15 – 18 ]. Infection with L .…”

Section: Introductionmentioning

confidence: 99%

The role of reactive oxygen intermediates in the intracellular fate of Leptospira interrogans in the macrophages of different hosts

Zhang

et al. 2017

PLoS ONE

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Section: Introductionmentioning

confidence: 99%

The role of reactive oxygen intermediates in the intracellular fate of Leptospira interrogans in the macrophages of different hosts

Zhang

et al. 2017

PLoS ONE

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“…Oxidative stress in the hepatocyte results in altered mitochondrial permeability and induces apoptosis[4]. Therefore, antioxidants could serve as possible drugs against INH- and RIF-induced hepatic toxic injury[5,6]. …”

Section: Introductionmentioning

confidence: 99%

Naringenin protects against isoniazid- and rifampicin-induced apoptosis in hepatic injury

Wang¹,

Fan²,

Zhang³

et al. 2016

WJG

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AIMTo explore the protective effects and mechanisms of naringenin (NRG) on hepatic injury induced by isoniazid (INH) and rifampicin (RIF).METHODSMale mice were randomly divided into four groups and treated for 14 d as follows: normal control group was administered intragastrically with normal saline solution alone; model group was administered intragastrically with INH (100 mg/kg) and RIF (100 mg/kg); low- and high-dosage NRG pretreatment groups were administered intragastrically with different doses of NRG (50 or 100 mg/kg) 2 h before INH and RIF challenge. Mice were killed 16 h after the last dose of drug treatment to determine activity of serum transaminases. Oxidative stress was evaluated by measuring hepatic glutathione (GSH) and superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Histopathological changes in hepatic tissue were observed under the optical microscope. Hepatocyte apoptosis was measured by TUNEL assay and caspase-3 activation. Expression of Bcl-2 and Bax in liver was determined by western blot.RESULTSBoth low- and high-dosage NRG pretreatment obviously alleviated serum levels of alanine aminotransferase and aspartate aminotransferase, liver index, hepatic MDA content, and increased hepatic GSH content and SOD activity compared with the INH and RIF-treated group (44.71 ± 8.15 U/L, 38.22 ± 6.64 U/L vs 58.15 ± 10.54 U/L; 98.36 ± 14.78 U/L, 92.41 ± 13.59 U/L vs 133.05 ± 19.36 U/L; 5.34% ± 0.26%, 4.93% ± 0.25% vs 5.71% ± 0.28%; 2.76 ± 0.67 nmol/mgprot, 2.64 ± 0.64 nmol/mgprot vs 4.49 ± 1.12 nmol/mgprot; 5.91 ± 1.31 mg/gprot, 6.42 ± 1.42 mg/gprot vs 3.11 ± 0.73 mg/gprot; 137.31 ± 24.62 U/mgprot, 148.83 ± 26.75 U/mgprot vs 102.34 ± 19.22 U/mgprot; all P < 0.01 or 0.05). Histopathological evaluation showed obvious necrosis and inflammatory cell infiltration in liver of mice administered INH and RIF; however, mice pretreated with NRG showed minor hepatic injury. In addition, INH and RIF resulted in hepatocyte apoptosis, and NRG pretreatment dramatically suppressed INH- and RIF-induced hepatocytes apoptosis. Furthermore, NRG-mediated anti-apoptotic effects seemed to be in connection with its regulation of Bax and Bcl-2 protein expression in hepatic tissue.CONCLUSIONNRG might attenuate INH- and RIF-induced hepatic injury via suppression of oxidative stress and hepatocyte apoptosis.

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“…Currently, new CFZ analogs are being tested for treatment of Mycobacterium avium infections associated with AIDS and for multidrugresistant tuberculosis (3)(4)(5)(6). Although primarily antimycobacterial, experimental evidence suggests a broader based activity toward Gram-positive bacteria (7,8) and strains of yeast (9).…”

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Reduction of Clofazimine by Mycobacterial Type 2 NADH:Quinone Oxidoreductase

Yano¹,

Kassovska-Bratinova²,

Teh³

et al. 2011

Journal of Biological Chemistry

288

162

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The mechanism of action of clofazimine (CFZ), an antimycobacterial drug with a long history, is not well understood. The present study describes a redox cycling pathway that involves the enzymatic reduction of CFZ by NDH-2, the primary respiratory chain NADH:quinone oxidoreductase of mycobacteria and nonenzymatic oxidation of reduced CFZ by O 2 yielding CFZ and reactive oxygen species (ROS). This pathway was demonstrated using isolated membranes and purified recombinant NDH-2. The reduction and oxidation of CFZ was measured spectrally, and the production of ROS was measured using a coupled assay system with Amplex Red. Supporting the ROS-based killing mechanism, bacteria grown in the presence of antioxidants are more resistant to CFZ. CFZ-mediated increase in NADH oxidation and ROS production were not observed in membranes from three different Gram-negative bacteria but was observed in Staphylococcus aureus and Saccharomyces cerevisiae, which is consistent with the known antimicrobial specificity of CFZ. A more soluble analog of CFZ, KS6, was synthesized and was shown to have the same activities as CFZ. These studies describe a pathway for a continuous and high rate of reactive oxygen species production in Mycobacterium smegmatis treated with CFZ and a CFZ analog as well as evidence that cell death produced by these agents are related to the production of these radical species.

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Interaction of Antimycobacterial Drugs with the Anti-Mycobacterium aviumComplex Effects of Antimicrobial Effectors, Reactive Oxygen Intermediates, Reactive Nitrogen Intermediates, and Free Fatty Acids Produced by Macrophages

Cited by 10 publications

References 35 publications

The role of reactive oxygen intermediates in the intracellular fate of Leptospira interrogans in the macrophages of different hosts

The role of reactive oxygen intermediates in the intracellular fate of Leptospira interrogans in the macrophages of different hosts

Naringenin protects against isoniazid- and rifampicin-induced apoptosis in hepatic injury

Reduction of Clofazimine by Mycobacterial Type 2 NADH:Quinone Oxidoreductase

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