Assessment of antioxidant activity of metformin in ethanol induced liver damage in Sprague Dawley rats

Borole, Kanchan Dnyanesh; Padalkar, Pradnya Hemant; Swami, Ravi

doi:10.18203/2319-2003.ijbcp20160739

Cited by 4 publications

(5 citation statements)

References 8 publications

(12 reference statements)

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“…A major mechanism that could explain the metabolic benefits of metformin is through the activation of AMP-activated protein kinase (AMPK) [ 18 ]. Improving insulin sensitivity, anti-inflammatory effects, reduction of TNF-α, inducible nitric oxide synthase (iNOS), interleukin1β, and antioxidant effects have been also suggested [ 13 , 19 , 20 , 21 ]. The apparent explanation of these results could suggest that the modification of gut microbiota by metformin is not a key player in the prevention of NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Detection and Quantification of Some Ethanol-Producing Bacterial Strains in the Gut of Mouse Model of Non-Alcoholic Fatty Liver Disease: Role of Metformin

et al. 2023

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Ethanol-producing dysbiotic gut microbiota could accelerate the progress of non-alcoholic fatty liver disease (NAFLD). Metformin demonstrated some benefits in NAFLD. In the present study, we tested the ability of metformin to modify ethanol-producing gut bacterial strains and, consequently, retard the progress of NAFLD. This 12-week study included forty mice divided into four groups (n = 10); normal diet, Western diet, Western diet with intraperitoneal metformin, and Western diet with oral metformin. Oral metformin has a slight advantage over intraperitoneal metformin in ameliorating the Western diet–induced changes in liver function tests and serum levels of different cytokines (IL-1β, IL-6, IL-17, and TNF-α). Changes in liver histology, fibrosis, lipid content, Ki67, and TNF-α were all corrected as well. Faecal ethanol contents were increased by the Western diet but did not improve after treatment with metformin although the numbers of ethanol-producing Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) were decreased by oral metformin. Metformin did not affect bacterial ethanol production. It does not seem that modification of ethanol-producing K. pneumoniae and E. coli bacterial strains by metformin could have a significant impact on the therapeutic potentials of metformin in this experimental model of NAFLD.

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Section: Discussionmentioning

confidence: 99%

Detection and Quantification of Some Ethanol-Producing Bacterial Strains in the Gut of Mouse Model of Non-Alcoholic Fatty Liver Disease: Role of Metformin

et al. 2023

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“…Metformin has a direct scavenging impact on ROS, which helps to restore the antioxidant system and reduce stress [18] . Several previous studies have been focused on the antioxidant effect of metformin in lowering oxidative damage markers such as Rizk et al (2018) [10] , Kelly et al (2015) [9] , Al-Hashem et al (2018) [19] and Borole et al (2016) [11] , have found metformin inhibits mitochondrial complex I, which may play an important role in the generation of cellular ROS, resulting in increased lipid peroxidation and raised MDA levels. It is widely understood that MDA/nmol/ml Groups blocking this complex with metformin reduced ROS production [20], [21] and consequent lipid peroxidation, resulting in decreased MDA and elevated GSH levels.…”

Section: Discussionmentioning

confidence: 99%

“…group 1: negative control: rats were given 1 ml of distilled water by oral gavage for 30 days, group 2: rats received metformin (250 mg/kg/day for 30 days) via oral gavage, group 3: rats received V.A (400 mg/kg) starting from the 22nd day of the experiment for eight days to induce hepatotoxicity by intraperitoneal route, groups 4: animals were received metformin orally via gavage at doses of 250 mg/kg/day for 30 days and valproic acid (400 mg/kg) starting from the 22nd day of the experiment for 8 days by intraperitoneal route. The doses of metformin were chosen according to human equation dose and previous studies [11] , and V.A dose determination depended on a preliminary study.…”

Section: Treatments and Animal Groupingmentioning

confidence: 99%

“…It is widely known that inhibiting this complex with metformin lowered ROS production and lipid peroxidation, resulting in lowers MDA and higher GSH levels [8] , [9] . The metformin has been found to protect against hepatotoxicity caused by methotrexate [10] , ethanol [11] , and other chemicals. However, the hepatoprotective effect of metformin on V.A-induced hepatic injury has not been explored.…”

Section: Introductionmentioning

confidence: 99%

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Antioxidative effect of metformin on valproic acid induced hepatoxicity in male rats

Numan

Mohamed

Ali

2022

AJPS

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Metformin is 1,1-dimethylbiguanide hydrochloride, is the first-line therapy for type 2 diabetes. Additionally, several studies focused on the role of metformin in antioxidant activities for the treatment of hepatic disorders. The experimentally -based result on valproic acid's liver injury, a front-line medicine for the treatment of epilepsy, attracted a lot of interest. As a result, the effect of metformin on valproic acid-induced redox disturbances in rat hepatic tissue was studied. metformin at 250 mg/kg dose was administered via oral gavage for 30 days, and valproic acid at a dose of 400 mg/kg was administered by intraperitoneal route starting from the twenty-second day of the experiment, for eight days to induce hepatotoxicity. Treatment with metformin reduced valproic acid-enhancing alanine aminotransferase, aspartate aminotransferase activities. Tissue levels of malondialdehyde in the liver tissue of valproic acid-treated rats significantly increased (P-value < 0.05) whereas glutathione decreased. The coadministration of metformin with valproic acid significantly decreased the malondialdehyde levels and increased glutathione levels (P-value < 0.05). Finally, metformin protected rats from valproic acid-induced hepatotoxicity, improved antioxidant status, and reduced hepatic oxidative stress.

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“…Thereby, metformin reduced the risk of cancer in diabetic patients compared to those using other anti‐diabetic drugs . Studies suggest that liver protection by metformin is mediated through reduction in oxidative stress …”

Section: Introductionmentioning

confidence: 99%

Metformin modulates cardiac endothelial dysfunction, oxidative stress and inflammation in irradiated rats: A new perspective of an antidiabetic drug

Karam

Radwan

2019

Clin Exp Pharma Physio

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Cardiovascular disease is one of the most pivotal disorders after radiotherapy. The aim of this study investigates the possible protective effect of metformin against gamma radiation‐induced heart damage in male rats. Group 1 (control) received saline, group 2 was whole body gamma‐irradiated 5 Gy, group 3 was orally administered metformin 50 mg/kg/day for 2 weeks, group 4 received metformin 50 mg/kg/day for 1 week, then exposed to whole‐body gamma radiation at a dose of 5 Gy and continued with metformin for further 1 week. The results revealed that the administration of metformin to irradiated rats significantly ameliorated the changes in cardiac biomarkers (LDH and CK‐MB) compared with irradiated group. Heart catalase and SOD activities showed normal level when compared with the irradiated group. Also, NF‐κB, IL‐6 and TNF‐ α levels were markedly decreased compared with the corresponding values of irradiated group. Consequently, metformin reduced E‐selectin as well ICAM and VCAM‐1. These results confirmed by histopathological examination. In conclusion, concomitant administration of metformin during radiotherapy acts as a potent heart protector from oxidative stress, inflammatory mediators and endothelial dysfunction induced damages. Results thus hold a great promise for a new implication of an antidiabetic drug (metformin) as adjunct to radiotherapy.

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Assessment of antioxidant activity of metformin in ethanol induced liver damage in Sprague Dawley rats

Cited by 4 publications

References 8 publications

Detection and Quantification of Some Ethanol-Producing Bacterial Strains in the Gut of Mouse Model of Non-Alcoholic Fatty Liver Disease: Role of Metformin

Detection and Quantification of Some Ethanol-Producing Bacterial Strains in the Gut of Mouse Model of Non-Alcoholic Fatty Liver Disease: Role of Metformin

Antioxidative effect of metformin on valproic acid induced hepatoxicity in male rats

Metformin modulates cardiac endothelial dysfunction, oxidative stress and inflammation in irradiated rats: A new perspective of an antidiabetic drug

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