Antioxidant Effect of MnTE-2-PyP on Lung in Asthma Mice Model

Terziev, L.; Dancheva, Violeta; Shopova, Veneta; Stavreva, Galya

doi:10.1100/2012/379360

Cited by 10 publications

(3 citation statements)

References 43 publications

(50 reference statements)

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“…MnTE-2-PyP is a low-molecular-weight drug that is relatively inexpensive and easy to produce, and is a SOD mimetic that reduces superoxide levels and has previously been described as a radioprotector in different tissue types (9, 32). MnTE-2-PyP acts as an antioxidant in asthma mouse models and other nonmalignant tissues (33, 34). But in certain malignant cell types, it has been described as pro-oxidant (35, 36).…”

Section: Discussionmentioning

confidence: 99%

MnTE-2-PyP Treatment, or NOX4 Inhibition, Protects against Radiation-Induced Damage in Mouse Primary Prostate Fibroblasts by Inhibiting the TGF-Beta 1 Signaling Pathway

2017

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Prostate cancer patients who undergo radiotherapy frequently suffer from side effects caused by radiation-induced damage to normal tissues adjacent to the tumor. Exposure of these normal cells during radiation treatment can result in tissue fibrosis and cellular senescence, which ultimately leads to postirradiation-related chronic complications including urinary urgency and frequency, erectile dysfunction, urethral stricture and incontinence. Radiation-induced reactive oxygen species (ROS) have been reported as the most potent causative factor for radiation damage to normal tissue. While MnTE-2-PyP, a ROS scavenger, protects normal cells from radiation-induced damage, it does not protect cancer cells during radiation treatment. However, the mechanism by which MnTE-2-PyP provides protection from radiation-induced fibrosis has been unclear. Our current study reveals the underlying molecular mechanism of radiation protection by MnTE-2-PyP in normal mouse prostate fibroblast cells. To investigate the role of MnTE-2-PyP in normal tissue protection after irradiation, primary prostate fibroblasts from C57BL/6 mice were cultured in the presence or absence of MnTE-2-PyP and exposed to 2 Gy of X rays. We found that MnTE-2-PyP could protect primary prostate fibroblasts from radiation-induced activation, as measured by the contraction of collagen discs, and senescence, detected by beta-galactosidase staining. We observed that MnTE-2-PyP inhibited the TGF-β-mediated fibroblast activation pathway by downregulating the expression of TGF-β receptor 2, which in turn reduced the activation and/or expression of SMAD2, SMAD3 and SMAD4. As a result, SMAD2/3-mediated transcription of profibrotic markers was reduced by MnTE-2-PyP. Due to the inhibition of the TGF-β pathway, fibroblasts treated with MnTE-2-PyP could resist radiation-induced activation and senescence. NADPH oxidase 4 (NOX4) expression is upregulated after irradiation and produces ROS. As was observed with MnTE-2-PyP treatment, NOX4−/− fibroblasts were protected from radiation-induced fibroblast activation and senescence. However, NOX4−/− fibroblasts had reduced levels of active TGF-β1, which resulted in decreased TGF-β signaling. Therefore, our data suggest that reduction of ROS levels, either by MnTE-2-PyP treatment or by eliminating NOX4 activity, significantly protects normal prostate tissues from radiation-induced tissue damage, but that these approaches work on different components of the TGF-β signaling pathway. This study proposes a crucial insight into the molecular mechanism executed by MnTE-2-PyP when utilized as a radioprotector. An understanding of how this molecule works as a radioprotector will lead to a better controlled mode of treatment for post therapy complications in prostate cancer patients.

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Section: Discussionmentioning

confidence: 99%

MnTE-2-PyP Treatment, or NOX4 Inhibition, Protects against Radiation-Induced Damage in Mouse Primary Prostate Fibroblasts by Inhibiting the TGF-Beta 1 Signaling Pathway

2017

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“…In accordance with our results, Patel et al found that symptomatic asthma in adults was associated with low dietary intake of Mn [ 49 ], and the lowest intakes of Mn were associated with a more than 5 times higher risk of bronchial reactivity [ 50 ]. Several studies also revealed that Mn-related antioxidants could mitigate the effects of oxidative stress in an asthma mice model, and a Mn -porphyrin compound could suppress both epithelial thickening and mucus accumulation in the epithelium [ 51 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Association between Concentrations of Metals in Urine and Adult Asthma: A Case-Control Study in Wuhan, China

Huang¹,

Xie

Cui³

et al. 2016

PLoS ONE

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BackgroundSeveral metals have been reported to be associated with childhood asthma. However, the results on relationships between metals and risk of childhood asthma are inconclusive, and the research on adult asthma in the Chinese general population is rare.ObjectivesTo investigate potential associations between levels of urinary metals and adult asthma.MethodsA case-control study of 551 adult asthma cases and 551 gender- and age-matched controls was conducted in Wuhan, China. Demographic information was obtained, and lung function was assessed. The urinary concentrations of 22 metals were measured by inductively coupled plasma mass spectrometry.ResultsAfter adjusting for other metalsand other covariates, urinary cadmium, molybdenum, chromium, copper, uranium and selenium were positively associated with asthma, with odds ratios (95% CI) of 1.69 (1.00, 2.85), 3.76 (2.30, 6.16), 4.89 (3.04, 7.89), 6.06 (3.27, 11.21), 6.99 (4.37, 11.19) and 9.17 (4.16, 20.21), respectively. By contrast, urinary lead, barium, iron, zinc, nickel, manganese and rubidium were negatively associated with asthma, with odds ratios (95% CI) of 0.48 (0.29, 0.80), 0.44 (0.27, 0.71), 0.41 (0.26, 0.64), 0.40 (0.24, 0.66), 0.30 (0.22, 0.41), 0.23 (0.14, 0.39) and 0.07 (0.03, 0.15), respectively. When comparing urinary metals in different subgroups of cases with those in matched controls, the associations of above 13 metals with asthma prevalence were nearly the same.ConclusionsOur results suggested that asthma prevalence in the Chinese adults was positively associated with urinary chromium, chromium, selenium, molybdenum, cadmium, and uranium, and negatively associated with urinary manganese, iron, nickel, zinc, rubidium, barium and lead. Additional research with larger populations in different regions is required to support our findings.

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“…Some biomolecules are also considered biologically active and clinically significant antioxidants, for example, transferrin, ferritin, lactoferrin, ceruloplasmin, hemopexin, haptoglobin, and uric acid. Antioxidative, that is, favorable effect of selected antioxidants, was studied in vivo by, for example, Terziev et al [ 1 ], Nguyen-Deroche et al [ 2 ] and Meira de-Faria et al [ 3 ], and in vitro by Gondoin et al [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Decrease in the Antioxidant Capacity in Beverages Containing Tea Extracts during Storage

Nekvapil

Kopřiva

Boudný

et al. 2012

The Scientific World Journal

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The aim of this work was to determine antioxidant capacity of beverages containing black, white, and green tea extracts using the photochemiluminescence method, and to monitor its changes based on the storage temperature and time. Samples were stored at two different temperatures (refrigerated at 4°C and laboratory temperature 22°C), analyzed after opening of the original package, and consequently after 4 and 7 days. Results of the antioxidant capacity are expressed as the standard equivalents, that is, ascorbic acid in mmol/L. The highest mean value of the antioxidant capacity was found after opening of the original package in fruit-juice-enriched samples and totaled 9.793 mmol/L. This group revealed significant dependence (P < 0.05) not only on the storage time, but also temperature. In samples without added fruit juices containing preservatives the value was 0.428 mmol/L. This group showed significant dependence (P < 0.05) on the decrease of antioxidant capacity only when based on the storage time. Samples without fruit juices or preservatives showed significant decrease in the antioxidant capacity (P < 0.05) after 4 days of storage based on the storage time. The dependence on temperature was revealed only after 7 days of storage.

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Antioxidant Effect of MnTE-2-PyP on Lung in Asthma Mice Model

Cited by 10 publications

References 43 publications

MnTE-2-PyP Treatment, or NOX4 Inhibition, Protects against Radiation-Induced Damage in Mouse Primary Prostate Fibroblasts by Inhibiting the TGF-Beta 1 Signaling Pathway

MnTE-2-PyP Treatment, or NOX4 Inhibition, Protects against Radiation-Induced Damage in Mouse Primary Prostate Fibroblasts by Inhibiting the TGF-Beta 1 Signaling Pathway

Association between Concentrations of Metals in Urine and Adult Asthma: A Case-Control Study in Wuhan, China

Decrease in the Antioxidant Capacity in Beverages Containing Tea Extracts during Storage

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