Regulation of Antioxidant Enzymes in Lung after Oxidant Injury

Quinlan, T.; Spivack, S.; Mossman, Brooke T.

doi:10.2307/3431823

Cited by 45 publications

(51 citation statements)

References 46 publications

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“…GST is another antioxidant enzyme, which contributes in cellular defense against ROS generation during oxidative stress of different tissues including lung (Day, 2008;Quinlan et al, 1994). As indicated in Table 1, a significant suppression occurs in GST activity of mice subjected to bleomycin exposure (48%).…”

Section: Discussionmentioning

confidence: 99%

Silymarin alleviates bleomycin-induced pulmonary toxicity and lipid peroxidation in mice

Razavi-Azarkhiavi

Aliomrani

Solgi

et al. 2014

Pharmaceutical Biology

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Context: The application of bleomycin is limited due to its side effects including lung toxicity. Silymarin is a flavonoid complex isolated from milk thistle [Silybum marianum L. (Asteraceae)] which has been identified as an antioxidant and anti-inflammatory compound.Objective: This study evaluates the effect of silymarin on oxidative and inflammatory parameters in the lungs of mice exposed to bleomycin. Materials and methods: BALB/c mice were divided into four groups of control, bleomycin (1.5 U/kg), bleomycin plus silymarin (50 and 100 mg/kg). After bleomycin administration, mice received 10 d intraperitoneal silymarin treatment. On 10th day, blood and lung samples were collected for measurement of oxidative and inflammatory factors. Results: Silymarin led to a decrease in lung lipid peroxidation (0.19 and 0.17 nmol/mg protein) in bleomycin-injected animals. Glutathione-S-transferase (GST) which was inhibited by bleomycin (32.4 nmol/min/mg protein) induced by higher dose of silymarin (41 nmol/min/mg protein). Silymarin caused an elevation in glutathione (GSH): 2.6 and 3.1 mmol/g lung compare with bleomycin-injected animals 1.8 mmol/g lung. Catalase (CAT) was increased due to high dose of silymarin (65.7 mmol/min/ml protein) compare with bleomycin treated-mice. Myeloperoxidase (MPO) which was induced due to bleomycin (p50.05) reduced again by high dose of silymarin (0.51 U/min/mg protein). Bleomycin led to an increase in TNF-a and interleukin-6 (IL-6) (7.9 and 11.8 pg/ml). These parameters were reduced by silymarin (p50.05). Conclusions: Silymarin attenuated bleomycin induced-pulmonary toxicity. This protective effect may be due to the ability of silymarin in keeping oxidant-antioxidant balance and regulating of inflammatory mediator release.

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Section: Discussionmentioning

confidence: 99%

Silymarin alleviates bleomycin-induced pulmonary toxicity and lipid peroxidation in mice

Razavi-Azarkhiavi

Aliomrani

Solgi

et al. 2014

Pharmaceutical Biology

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“…These conflicting findings might also indicate that measurements of the antioxidant status in whole blood might not be sensitive enough to detect cellular adaptive protection. Various animal experiments have shown an increase in antioxidant enzymes after hyperoxia (27) but only a few studies have investigated the effects of HBO. In experiments with rats and guinea pigs, exposure to HBO had marked effects on antioxidant enzymes in brain and lung (28).…”

Section: Discussionmentioning

confidence: 99%

Adaptive protection against the induction of oxidative DNA damage after hyperbaric oxygen treatment

Rothfuß

Dennog²,

Speit

1998

Carcinogenesis

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Hyperbaric oxygen (HBO) treatment (i.e. exposure to 100% oxygen at a pressure of 2.5 ATA for a total of three 20 min periods) of human subjects caused clear and reproducible DNA effects in the comet assay with leukocytes. Interestingly, DNA damage was detected only after the first treatment and not after further treatments under the same conditions, indicating an increase in antioxidant defences. We now demonstrate that blood taken 24 h after HBO treatment is well protected against the in vitro induction of DNA damage by hydrogen peroxide (H 2 O 2 ). H 2 O 2 treatment caused a significant induction of DNA effects in the comet assay and chromosome breakage in the micronucleus test in the blood of volunteers before HBO. The same treatment did not cause genotoxic effects 24 h after HBO. This protective effect lasted for at least 1 week. Experiments with isolated lymphocytes gave similar results, indicating that the adaptive response is a cellular effect. The cells were not comparably protected against the genotoxic effects of γ-irradiation, suggesting increased scavenging of reactive oxygen species distant from nuclear DNA.

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“…The ability of the antioxidants to inhibit Akt activation by bleomycin indicates the role of ROS in this process. Bleomycin-induced lung fibrosis has been reported to be associated with increased ROS production (37,38). To test whether ROS might mediate the fibrogenic effect of bleomycin through PI3K/Akt/HIF1a/VEGF signaling, we evaluated the effect of antioxidants on bleomycin-induced HIF-1a and VEGF activation.…”

Section: Requirement Of Ros For Bleomycin-induced Pi3k/akt Activationmentioning

confidence: 99%

Phosphatidylinositol-3-Kinase/Akt Regulates Bleomycin-Induced Fibroblast Proliferation and Collagen Production

Azad²,

Wang³

et al. 2010

Am J Respir Cell Mol Biol

110

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Abnormal repair and dysregulated angiogenesis have been implicated in the pathogenesis of pulmonary fibrosis, but the underlying mechanisms of regulation are not well understood. The present study investigated the role of phosphatidylinositol-3-kinase (PI3K)/ Akt in fibrogenesis of human lung fibroblasts and its regulation by reactive oxygen species (ROS). Exposure of lung fibroblasts to bleomycin, a known inducer of fibrosis, resulted in rapid activation of PI3K/Akt and a parallel increase in fibroblast proliferation and collagen production, characteristics of lung fibrosis. Bleomycin had no significant effect on total Akt protein expression but induced phosphorylation of the protein at threonine 308 and serine 473 positions. Inhibition of this phosphorylation by PI3K inhibitors or by dominant-negative Akt (T308A/S473A) expression abrogated the effects of bleomycin on fibroblast proliferation and collagen production, suggesting the role of PI3K/Akt in the fibrogenic process. Activation of PI3K/Akt by bleomycin also led to transcriptional activation and protein expression of hypoxia-inducible factor-1a (HIF-1a) and vascular endothelial growth factor, which contributed to the fibroproliferative and collagen-inducing effects of bleomycin. The fibrogenic effects of bleomycin were dependent on ROS generation, particularly superoxide anion and hydrogen peroxide, which were induced by bleomycin. Inhibition of ROS generation by antioxidant enzymes, catalase and superoxide dismutase mimetic MnTBAP, abrogated the fibrogenic effects of bleomycin as well as its induction of PI3K/Akt and HIF-1a activation. Together, our results indicate a novel role of PI3K/Akt in fibrogenesis of human lung fibroblasts and its regulation by ROS, which could be exploited for the treatment of pulmonary fibrosis and related disorders.

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Regulation of Antioxidant Enzymes in Lung after Oxidant Injury

Cited by 45 publications

References 46 publications

Silymarin alleviates bleomycin-induced pulmonary toxicity and lipid peroxidation in mice

Silymarin alleviates bleomycin-induced pulmonary toxicity and lipid peroxidation in mice

Adaptive protection against the induction of oxidative DNA damage after hyperbaric oxygen treatment

Phosphatidylinositol-3-Kinase/Akt Regulates Bleomycin-Induced Fibroblast Proliferation and Collagen Production

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