Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis
Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the colorectal area that demonstrates a dramatically increasing incidence worldwide. This study provides novel insights into the capacity of the exogenous β-hydroxybutyrate and ketogenic diet (KD) consumption to alleviate dextran...
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1239025/full |
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| author | Rasha Abdelhady Sameh Saber Mustafa Ahmed Abdel-Reheim Mustafa Ahmed Abdel-Reheim Mohannad Mohammad S. Alamri Jaber Alfaifi Masoud I. E. Adam Lobna A. Saleh Lobna A. Saleh Azza I. Farag Elsayed A. Elmorsy Elsayed A. Elmorsy Hend S. El-Wakeel Hend S. El-Wakeel Ahmed S. Doghish Ahmed S. Doghish Mohamed E. Shaker Sara H. Hazem Heba A. Ramadan Rabab S. Hamad Rabab S. Hamad Osama A. Mohammed Osama A. Mohammed |
| author_facet | Rasha Abdelhady Sameh Saber Mustafa Ahmed Abdel-Reheim Mustafa Ahmed Abdel-Reheim Mohannad Mohammad S. Alamri Jaber Alfaifi Masoud I. E. Adam Lobna A. Saleh Lobna A. Saleh Azza I. Farag Elsayed A. Elmorsy Elsayed A. Elmorsy Hend S. El-Wakeel Hend S. El-Wakeel Ahmed S. Doghish Ahmed S. Doghish Mohamed E. Shaker Sara H. Hazem Heba A. Ramadan Rabab S. Hamad Rabab S. Hamad Osama A. Mohammed Osama A. Mohammed |
| author_sort | Rasha Abdelhady |
| collection | DOAJ |
| description | Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the colorectal area that demonstrates a dramatically increasing incidence worldwide. This study provides novel insights into the capacity of the exogenous β-hydroxybutyrate and ketogenic diet (KD) consumption to alleviate dextran sodium sulfate (DSS)-induced UC in rats. Remarkably, both interventions attenuated disease activity and colon weight-to-length ratio, and improved macro and microstructures of the damaged colon. Importantly, both β-hydroxybutyrate and KD curbed the DSS-induced aberrant NLRP3 inflammasome activation as observed in mRNA and protein expression analysis. Additionally, inhibition of the NLRP3/NGSDMD-mediated pyroptosis was detected in response to both regimens. In parallel, these modalities attenuated caspase-1 and its associated consequences of IL-1β and IL-18 overproduction. They also mitigated apoptosis as indicated by the inactivation of caspase-3. The anti-inflammatory effects of BHB and KD were confirmed by the reported decline in the levels of inflammatory markers including MPO, NFκB, IL-6, and TNF-α. Moreover, these interventions exhibited antioxidative properties by reducing ROS production and improving antioxidative enzymes. Their effectiveness in mitigating UC was also evident in the renovation of normal intestinal epithelial barrier function, as shown by correcting the discrepancies in the levels of tight junction proteins ZO-1, OCLN, and CLDN5. Furthermore, their effects on the intestinal microbiota homeostasis were investigated. In terms of autophagy, exogenous β-hydroxybutyrate upregulated BECN-1 and downregulated p62, which may account for its superiority over KD in attenuating colonic damage. In conclusion, this study provides experimental evidence supporting the potential therapeutic use of β-hydroxybutyrate or β-hydroxybutyrate-boosting regimens in UC. |
| first_indexed | 2024-03-11T20:54:03Z |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-25T00:13:36Z |
| publishDate | 2023-09-01 |
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| spelling | doaj.art-963d754da07e445b9102ebb7075ec4312024-03-13T09:04:56ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-09-011410.3389/fphar.2023.12390251239025Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosisRasha Abdelhady0Sameh Saber1Mustafa Ahmed Abdel-Reheim2Mustafa Ahmed Abdel-Reheim3Mohannad Mohammad S. Alamri4Jaber Alfaifi5Masoud I. E. Adam6Lobna A. Saleh7Lobna A. Saleh8Azza I. Farag9Elsayed A. Elmorsy10Elsayed A. Elmorsy11Hend S. El-Wakeel12Hend S. El-Wakeel13Ahmed S. Doghish14Ahmed S. Doghish15Mohamed E. Shaker16Sara H. Hazem17Heba A. Ramadan18Rabab S. Hamad19Rabab S. Hamad20Osama A. Mohammed21Osama A. Mohammed22Pharmacology and Toxicology Department, Faculty of Pharmacy, Fayoum University, Fayoum, EgyptDepartment of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, EgyptDepartment of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, EgyptDepartment of Family Medicine, College of Medicine, University of Bisha, Bisha, Saudi ArabiaDepartment of Child Health, College of Medicine, University of Bisha, Bisha, Saudi ArabiaDepartment of Medical Education and Internal Medicine, College of Medicine, University of Bisha, Bisha, Saudi ArabiaDepartment of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, EgyptDepartment of Pharmacology and Toxicology, Collage of Pharmacy, Taif University, Taif, Saudi Arabia0Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig, Egypt1Department of Pharmacology and Therapeutics, Qassim College of Medicine, Qassim University, Buraydah, Saudi Arabia2Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt3Physiology Department, Benha Faculty of Medicine, Benha University, Banha, Egypt4Physiology Department, Al-baha Faculty of Medicine, Al-baha University, Al-Baha, Saudi Arabia5Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Cairo, Egypt6Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt7Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia8Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt9Department of Microbiology and Immunology, Faculty of Pharmacy, Delta University for Science and Technology, Al Mansurah, Egypt0Biological Sciences Department, College of Science, King Faisal University, Al Ahsa, Saudi Arabia1Central Laboratory, Theodor Bilharz Research Institute, Giza, EgyptDepartment of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt2Department of Clinical Pharmacology, College of Medicine, University of Bisha, Bisha, Saudi ArabiaUlcerative colitis (UC) is a chronic relapsing inflammatory disease of the colorectal area that demonstrates a dramatically increasing incidence worldwide. This study provides novel insights into the capacity of the exogenous β-hydroxybutyrate and ketogenic diet (KD) consumption to alleviate dextran sodium sulfate (DSS)-induced UC in rats. Remarkably, both interventions attenuated disease activity and colon weight-to-length ratio, and improved macro and microstructures of the damaged colon. Importantly, both β-hydroxybutyrate and KD curbed the DSS-induced aberrant NLRP3 inflammasome activation as observed in mRNA and protein expression analysis. Additionally, inhibition of the NLRP3/NGSDMD-mediated pyroptosis was detected in response to both regimens. In parallel, these modalities attenuated caspase-1 and its associated consequences of IL-1β and IL-18 overproduction. They also mitigated apoptosis as indicated by the inactivation of caspase-3. The anti-inflammatory effects of BHB and KD were confirmed by the reported decline in the levels of inflammatory markers including MPO, NFκB, IL-6, and TNF-α. Moreover, these interventions exhibited antioxidative properties by reducing ROS production and improving antioxidative enzymes. Their effectiveness in mitigating UC was also evident in the renovation of normal intestinal epithelial barrier function, as shown by correcting the discrepancies in the levels of tight junction proteins ZO-1, OCLN, and CLDN5. Furthermore, their effects on the intestinal microbiota homeostasis were investigated. In terms of autophagy, exogenous β-hydroxybutyrate upregulated BECN-1 and downregulated p62, which may account for its superiority over KD in attenuating colonic damage. In conclusion, this study provides experimental evidence supporting the potential therapeutic use of β-hydroxybutyrate or β-hydroxybutyrate-boosting regimens in UC.https://www.frontiersin.org/articles/10.3389/fphar.2023.1239025/fullulcerative colitisβ-hydroxybutyrateNLRP3 inflammasomeapoptosispyroptosis |
| spellingShingle | Rasha Abdelhady Sameh Saber Mustafa Ahmed Abdel-Reheim Mustafa Ahmed Abdel-Reheim Mohannad Mohammad S. Alamri Jaber Alfaifi Masoud I. E. Adam Lobna A. Saleh Lobna A. Saleh Azza I. Farag Elsayed A. Elmorsy Elsayed A. Elmorsy Hend S. El-Wakeel Hend S. El-Wakeel Ahmed S. Doghish Ahmed S. Doghish Mohamed E. Shaker Sara H. Hazem Heba A. Ramadan Rabab S. Hamad Rabab S. Hamad Osama A. Mohammed Osama A. Mohammed Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis Frontiers in Pharmacology ulcerative colitis β-hydroxybutyrate NLRP3 inflammasome apoptosis pyroptosis |
| title | Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis |
| title_full | Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis |
| title_fullStr | Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis |
| title_full_unstemmed | Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis |
| title_short | Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis |
| title_sort | unveiling the therapeutic potential of exogenous β hydroxybutyrate for chronic colitis in rats novel insights on autophagy apoptosis and pyroptosis |
| topic | ulcerative colitis β-hydroxybutyrate NLRP3 inflammasome apoptosis pyroptosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1239025/full |
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