Minocycline and Doxycycline, But Not Tetracycline, Mitigate Liver and Kidney Injury After Hemorrhagic Shock/Resuscitation

Kholmukhamedov, Andaleb; Czerny, C.; Hu, Jian; Schwartz, Justin; Zhong, Zhi; Lemasters, John J.

doi:10.1097/shk.0000000000000213

Cited by 23 publications

(10 citation statements)

References 39 publications

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“…Significant weight loss as a consequence of fat loss and muscle wasting, indicative of cachexia, was seen in our TET-induced OSM in MDA TO/OSM xenograft mouse model. TET alone does not appear to have any effect on kidney function [ 51 ]. Interestingly, TET has been shown to actually reduce tumor cell growth and aggressiveness [ 52 ], but this effect was not seen in our studies.…”

Section: Discussionmentioning

confidence: 99%

OSM potentiates preintravasation events, increases CTC counts, and promotes breast cancer metastasis to the lung

et al. 2018

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BackgroundSystemic and chronic inflammatory conditions in patients with breast cancer have been associated with reduced patient survival and increased breast cancer aggressiveness. This paper characterizes the role of an inflammatory cytokine, oncostatin M (OSM), in the preintravasation aspects of breast cancer metastasis.MethodsOSM expression levels in human breast cancer tissue samples were assessed using tissue microarrays, and expression patterns based on clinical stage were assessed. To determine the in vivo role of OSM in breast cancer metastasis to the lung, we used three orthotopic breast cancer mouse models, including a syngeneic 4T1.2 mouse mammary cancer model, the MDA-MB-231 human breast cancer xenograft model, and an OSM-knockout (OSM-KO) mouse model. Progression of metastatic disease was tracked by magnetic resonance imaging and bioluminescence imaging. Endpoint analysis included circulating tumor cell (CTC) counts, lung metastatic burden analysis by qPCR, and ex vivo bioluminescence imaging.ResultsUsing tissue microarrays, we found that tumor cell OSM was expressed at the highest levels in ductal carcinoma in situ. This finding suggests that OSM may function during the earlier steps of breast cancer metastasis. In mice bearing MDA-MB-231-Luc2 xenograft tumors, peritumoral injection of recombinant human OSM not only increased metastases to the lung and decreased survival but also increased CTC numbers. To our knowledge, this is the first time that a gp130 family inflammatory cytokine has been shown to directly affect CTC numbers. Using a 4T1.2 syngeneic mouse model of breast cancer, we found that mice bearing 4T1.2-shOSM tumors with knocked down tumor expression of OSM had reduced CTCs, decreased lung metastatic burden, and increased survival compared with mice bearing control tumors. CTC numbers were further reduced in OSM-KO mice bearing the same tumors, demonstrating the importance of both paracrine- and autocrine-produced OSM in this process. In vitro studies further supported the hypothesis that OSM promotes preintravasation aspects of cancer metastasis, because OSM induced both 4T1.2 tumor cell detachment and migration.ConclusionsCollectively, our findings suggest that OSM plays a crucial role in the early steps of metastatic breast cancer progression, resulting in increased CTCs and lung metastases as well as reduced survival. Therefore, early therapeutic inhibition of OSM in patients with breast cancer may prevent breast cancer metastasis.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-0971-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

OSM potentiates preintravasation events, increases CTC counts, and promotes breast cancer metastasis to the lung

et al. 2018

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“…Doxycycline as another tetracycline antibiotics exhibited renoprotective effects by decreasing levels of IL-1β, TNF-α and MMP-2 in renal tissue against IRI induced by abdominal compartment syndrome (ACS) (Ihtiyar et al, 2011). Both minocycline and doxycycline were effective in mitigating liver and kidney injury to improve survival in the mouse model of hemorrhagic shock/resuscitation (Kholmukhamedov et al, 2014). …”

Section: Chemical Renoprotectantsmentioning

confidence: 99%

Renoprotective approaches and strategies in acute kidney injury

Yang

Song

et al. 2016

Pharmacology & Therapeutics

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Acute kidney injury (AKI) is a major renal disease associated with a high mortality rate and increasing prevalence. Decades of research has suggested numerous chemical and biological agents with beneficial effects in AKI. In addition, cell therapy and molecular targeting have been explored for reducing kidney tissue damage and promoting kidney repair or recovery from AKI. Mechanistically, these approaches may mitigate oxidative stress, inflammation, cell death, and mitochondrial and other organellar damage, or activate cytoprotective mechanisms such as autophagy and pro-survival factors. However, none of these findings has been successfully translated into clinical treatment of AKI. In this review, we analyze these findings and propose experimental strategies for the identification of renoprotective agents or methods with clinical potential. Moreover, we propose the consideration of combination therapy by targeting multiple targets in AKI.

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“…TETRA prevented Ca 2+ uptake by mitochondria and then inhibited the inducement of mitochondrial permeability transmission by Ca 2+ . 33 …”

Section: Discussionmentioning

confidence: 99%

Potential adverse effects of ciprofloxacin and tetracycline on ARPE-19 cell lines

et al. 2020

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BackgroundWe aim to determine the possible adverse effects of ciprofloxacin (CPFX) and tetracycline (TETRA), as examples of bactericidal and bacteriostatic agents, respectively, on cultured human retinal pigment epithelial cells (ARPE-19).MethodsCells were treated with 30, 60 and 120 µg/mL of CPFX and TETRA. Cell metabolism was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. JC-1 dye (5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide) assay was conducted to measure the mitochondrial membrane potential (MMP). The level of reactive oxygen species (ROS) was measured using the -2’,7’-dichlorodihydrofluorescein diacetate assay (H2DCFDA). Quantitative real-time PCR was performed to analyse the gene expression levels associated with apoptosis (BAX, BCL2-L13, BCL2, Caspase 3, Caspase 7 and Caspase 9), inflammatory (interleukin-1β (IL-1β), IL-6, IL-33, transforming growth factor-α (TGF-α), TGF-β1 and TGF-β2) and antioxidant pathways (SOD2, SOD3, GPX3 and NOX4), along with the mitochondrial DNA (mtDNA) copy numbers.ResultsResults illustrated that while all three concentrations of CPFX decreased cellular viability of ARPE-19 during all incubation periods, the 120 µg/mL TETRA resulted in increased cellular viability. At 48 and 72 hours, levels of MMP and ROS decreased significantly with each antibiotic. BAX, BCL2-L13, CASP-7, CASP-9, SOD2 and GPX3 genes overexpressed by either antibiotics. There was higher expression of IL-6 and IL-1B with TETRA treatment. The level of mtDNA decreased using both treatments.ConclusionsClinically relevant concentrations of CPFX and TETRA have detrimental impacts on ARPE-19 cell lines in vitro, including upregulation of genes related to apoptosis, inflammation and antioxidant pathways. Additional studies are warranted to investigate if these harmful effects might be seen in retinal degeneration models in vivo.

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Minocycline and Doxycycline, But Not Tetracycline, Mitigate Liver and Kidney Injury After Hemorrhagic Shock/Resuscitation

Cited by 23 publications

References 39 publications

OSM potentiates preintravasation events, increases CTC counts, and promotes breast cancer metastasis to the lung

OSM potentiates preintravasation events, increases CTC counts, and promotes breast cancer metastasis to the lung

Renoprotective approaches and strategies in acute kidney injury

Potential adverse effects of ciprofloxacin and tetracycline on ARPE-19 cell lines

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