Metformin and Probiotics Interplay in Amelioration of Ethanol-Induced Oxidative Stress and Inflammatory Response in an In Vitro and In Vivo Model of Hepatic Injury
Alcohol-induced liver injury implicates inflammation and oxidative stress as important mediators. Despite rigorous research, there is still no Food and Drug Administration (FDA) approved therapies for any stage of alcoholic liver disease (ALD). Interestingly, metformin (Met) and several probiotic st...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/6636152 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832567397645549568 |
|---|---|
| author | Farhin Patel Kirti Parwani Dhara Patel Palash Mandal |
| author_facet | Farhin Patel Kirti Parwani Dhara Patel Palash Mandal |
| author_sort | Farhin Patel |
| collection | DOAJ |
| description | Alcohol-induced liver injury implicates inflammation and oxidative stress as important mediators. Despite rigorous research, there is still no Food and Drug Administration (FDA) approved therapies for any stage of alcoholic liver disease (ALD). Interestingly, metformin (Met) and several probiotic strains possess the potential of inhibiting alcoholic liver injury. Therefore, we investigated the effectiveness of combination therapy using a mixture of eight strains of lactic acid-producing bacteria, commercialized as Visbiome® (V) and Met in preventing the ethanol-induced hepatic injury using in vitro and in vivo models. Human HepG2 cells and male Wistar rats were exposed to ethanol and simultaneously treated with probiotic V or Met alone as well as in combination. Endoplasmic reticulum (ER) stress markers, inflammatory markers, lipid metabolism, reactive oxygen species (ROS) production, and oxidative stress were evaluated, using qRT-PCR, Oil red O staining, fluorimetry, and HPLC. In vitro, probiotic V and Met in combination prevented ethanol-induced cellular injury, ER stress, oxidative stress, and regulated lipid metabolism as well as inflammatory response in HepG2 cells. Probiotic V and Met also promoted macrophage polarization towards the M2 phenotype in ethanol-exposed RAW 264.7 macrophage cells. In vivo, combined administration of probiotic V and Met ameliorated the histopathological changes, inflammatory response, hepatic markers (liver enzymes), and lipid metabolism induced by ethanol. It also improved the antioxidant markers (HO-1 and Nrf-2), as seen by their protein levels in both HepG2 cells as well as liver tissue using ELISA. Hence, probiotic V may act, in addition to the Met, as an effective preventive treatment against ethanol-induced hepatic injury. |
| format | Article |
| id | doaj-art-b5ce3e8cb839476194e56eefae72a537 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-b5ce3e8cb839476194e56eefae72a5372025-02-03T01:01:34ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/66361526636152Metformin and Probiotics Interplay in Amelioration of Ethanol-Induced Oxidative Stress and Inflammatory Response in an In Vitro and In Vivo Model of Hepatic InjuryFarhin Patel0Kirti Parwani1Dhara Patel2Palash Mandal3Department of Biological Sciences, P. D. Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa, 388421 Anand, Gujarat, IndiaDepartment of Biological Sciences, P. D. Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa, 388421 Anand, Gujarat, IndiaDepartment of Biological Sciences, P. D. Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa, 388421 Anand, Gujarat, IndiaDepartment of Biological Sciences, P. D. Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa, 388421 Anand, Gujarat, IndiaAlcohol-induced liver injury implicates inflammation and oxidative stress as important mediators. Despite rigorous research, there is still no Food and Drug Administration (FDA) approved therapies for any stage of alcoholic liver disease (ALD). Interestingly, metformin (Met) and several probiotic strains possess the potential of inhibiting alcoholic liver injury. Therefore, we investigated the effectiveness of combination therapy using a mixture of eight strains of lactic acid-producing bacteria, commercialized as Visbiome® (V) and Met in preventing the ethanol-induced hepatic injury using in vitro and in vivo models. Human HepG2 cells and male Wistar rats were exposed to ethanol and simultaneously treated with probiotic V or Met alone as well as in combination. Endoplasmic reticulum (ER) stress markers, inflammatory markers, lipid metabolism, reactive oxygen species (ROS) production, and oxidative stress were evaluated, using qRT-PCR, Oil red O staining, fluorimetry, and HPLC. In vitro, probiotic V and Met in combination prevented ethanol-induced cellular injury, ER stress, oxidative stress, and regulated lipid metabolism as well as inflammatory response in HepG2 cells. Probiotic V and Met also promoted macrophage polarization towards the M2 phenotype in ethanol-exposed RAW 264.7 macrophage cells. In vivo, combined administration of probiotic V and Met ameliorated the histopathological changes, inflammatory response, hepatic markers (liver enzymes), and lipid metabolism induced by ethanol. It also improved the antioxidant markers (HO-1 and Nrf-2), as seen by their protein levels in both HepG2 cells as well as liver tissue using ELISA. Hence, probiotic V may act, in addition to the Met, as an effective preventive treatment against ethanol-induced hepatic injury.http://dx.doi.org/10.1155/2021/6636152 |
| spellingShingle | Farhin Patel Kirti Parwani Dhara Patel Palash Mandal Metformin and Probiotics Interplay in Amelioration of Ethanol-Induced Oxidative Stress and Inflammatory Response in an In Vitro and In Vivo Model of Hepatic Injury Mediators of Inflammation |
| title | Metformin and Probiotics Interplay in Amelioration of Ethanol-Induced Oxidative Stress and Inflammatory Response in an In Vitro and In Vivo Model of Hepatic Injury |
| title_full | Metformin and Probiotics Interplay in Amelioration of Ethanol-Induced Oxidative Stress and Inflammatory Response in an In Vitro and In Vivo Model of Hepatic Injury |
| title_fullStr | Metformin and Probiotics Interplay in Amelioration of Ethanol-Induced Oxidative Stress and Inflammatory Response in an In Vitro and In Vivo Model of Hepatic Injury |
| title_full_unstemmed | Metformin and Probiotics Interplay in Amelioration of Ethanol-Induced Oxidative Stress and Inflammatory Response in an In Vitro and In Vivo Model of Hepatic Injury |
| title_short | Metformin and Probiotics Interplay in Amelioration of Ethanol-Induced Oxidative Stress and Inflammatory Response in an In Vitro and In Vivo Model of Hepatic Injury |
| title_sort | metformin and probiotics interplay in amelioration of ethanol induced oxidative stress and inflammatory response in an in vitro and in vivo model of hepatic injury |
| url | http://dx.doi.org/10.1155/2021/6636152 |
| work_keys_str_mv | AT farhinpatel metforminandprobioticsinterplayinameliorationofethanolinducedoxidativestressandinflammatoryresponseinaninvitroandinvivomodelofhepaticinjury AT kirtiparwani metforminandprobioticsinterplayinameliorationofethanolinducedoxidativestressandinflammatoryresponseinaninvitroandinvivomodelofhepaticinjury AT dharapatel metforminandprobioticsinterplayinameliorationofethanolinducedoxidativestressandinflammatoryresponseinaninvitroandinvivomodelofhepaticinjury AT palashmandal metforminandprobioticsinterplayinameliorationofethanolinducedoxidativestressandinflammatoryresponseinaninvitroandinvivomodelofhepaticinjury |