Alpha-linolenic acid based nano-suspension protect against lipopolysaccharides induced mastitis by inhibiting NFκBp65, HIF-1α, and mitochondria-mediated apoptotic pathway in albino Wistar rats
Copyright © 2019 Elsevier Inc. All rights reserved..
The purpose of this study was to investigate the therapeutic effects and underlying mechanism of alpha-linolenic acid based intra-mammary nano-suspension (ALA-NS) on both in vitro antimicrobial and in vivo activity. The ALA-NS formulated and optimized for parameters like particle size, zeta potential, polydispersity index, sedimentation volume, and stability studies. In vitro, our results showed that ALA-NS (F1 and F2) have the higher zone of inhibition and lower minimum inhibitory concentration (MIC) value than ALA and cefotaxime alone against mastitis-causing pathogens. In vivo, our results showed that ALA-NS (F1 and F2) restored the altered oxidative biomarkers (superoxide dismutase, catalase, glutathione, TBARs, and protein carbonyl) along with histopathological changes in lipopolysaccharides (LPS) treated rats. Western blot results indicated that ALA-NS (F1 and F2) inhibited LPS induced inflammatory proteins (NFκBp65, COX, LOX, and IFN-γ) in rat mammary epithelial cells. ALA-NS (F1 and F2) also suppressed the hypoxia inducible factor-1α (HIF-1α) and upregulated prolyl-hydroxylase (PHD-2), sterol regulatory element binding protein (SREBP-1c), and fatty acid synthase (FASN) protein expression. In addition, ALA-NS upregulated the pro-apoptotic (BAX and BAD) and downregulated anti-apoptotic (BCL-2 and BCL-XL) proteins expression in rat mammary epithelial tissue. In conclusion, we found that ALA-NS (F1 and F2) have in vitro antimicrobial activity and protective effects on LPS-induced mastitis in rats.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:377 |
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| Enthalten in: |
Toxicology and applied pharmacology - 377(2019) vom: 15. Aug., Seite 114628 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yadav, Rajnish Kumar [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.05.2020 Date Revised 19.05.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.taap.2019.114628 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM29823744X |
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| 100 | 1 | |a Yadav, Rajnish Kumar |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Alpha-linolenic acid based nano-suspension protect against lipopolysaccharides induced mastitis by inhibiting NFκBp65, HIF-1α, and mitochondria-mediated apoptotic pathway in albino Wistar rats |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 Elsevier Inc. All rights reserved. | ||
| 520 | |a The purpose of this study was to investigate the therapeutic effects and underlying mechanism of alpha-linolenic acid based intra-mammary nano-suspension (ALA-NS) on both in vitro antimicrobial and in vivo activity. The ALA-NS formulated and optimized for parameters like particle size, zeta potential, polydispersity index, sedimentation volume, and stability studies. In vitro, our results showed that ALA-NS (F1 and F2) have the higher zone of inhibition and lower minimum inhibitory concentration (MIC) value than ALA and cefotaxime alone against mastitis-causing pathogens. In vivo, our results showed that ALA-NS (F1 and F2) restored the altered oxidative biomarkers (superoxide dismutase, catalase, glutathione, TBARs, and protein carbonyl) along with histopathological changes in lipopolysaccharides (LPS) treated rats. Western blot results indicated that ALA-NS (F1 and F2) inhibited LPS induced inflammatory proteins (NFκBp65, COX, LOX, and IFN-γ) in rat mammary epithelial cells. ALA-NS (F1 and F2) also suppressed the hypoxia inducible factor-1α (HIF-1α) and upregulated prolyl-hydroxylase (PHD-2), sterol regulatory element binding protein (SREBP-1c), and fatty acid synthase (FASN) protein expression. In addition, ALA-NS upregulated the pro-apoptotic (BAX and BAD) and downregulated anti-apoptotic (BCL-2 and BCL-XL) proteins expression in rat mammary epithelial tissue. In conclusion, we found that ALA-NS (F1 and F2) have in vitro antimicrobial activity and protective effects on LPS-induced mastitis in rats | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Alpha-linolenic acid | |
| 650 | 4 | |a Hypoxia | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Lipopolysaccharides | |
| 650 | 4 | |a Mastitis | |
| 650 | 7 | |a Anti-Infective Agents |2 NLM | |
| 650 | 7 | |a Apoptosis Regulatory Proteins |2 NLM | |
| 650 | 7 | |a Hif1a protein, rat |2 NLM | |
| 650 | 7 | |a Hypoxia-Inducible Factor 1, alpha Subunit |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a Suspensions |2 NLM | |
| 650 | 7 | |a Transcription Factor RelA |2 NLM | |
| 650 | 7 | |a alpha-Linolenic Acid |2 NLM | |
| 650 | 7 | |a 0RBV727H71 |2 NLM | |
| 700 | 1 | |a Tripathi, Chandra Bhusan |e verfasserin |4 aut | |
| 700 | 1 | |a Saraf, Shubhini A |e verfasserin |4 aut | |
| 700 | 1 | |a Ansari, Mohd Nazam |e verfasserin |4 aut | |
| 700 | 1 | |a Saeedan, Abdulaziz S |e verfasserin |4 aut | |
| 700 | 1 | |a Aldosary, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Rajinikanth, Paruvathanahalli S |e verfasserin |4 aut | |
| 700 | 1 | |a Kaithwas, Gaurav |e verfasserin |4 aut | |
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