Metformin ameliorates acetaminophen-induced sub-acute toxicity via antioxidant property

Tripathi, Shambhoo Sharan; Singh, Sandeep; Garg, Geetika; Kumar, Raushan; Verma, Avnish Kumar; Singh, Abhishek Kumar; Bissoyi, Akalabya; Rizvi, Syed Ibrahim

doi:10.1080/01480545.2019.1658769

Cited by 26 publications

(9 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hepatotoxicity of acetaminophen may not be attributed to its membrane interaction but to hepatocyte cellular death and mitochondrial dysfunction caused by increased reactive oxygen and nitrogen species (oxidative/nitrosative stress). Overdose administered acetaminophen is metabolized to N -acetyl- p -benzoquinone imine (NAPQI) [4], which overproduces reactive oxygen species with the subsequent induction of lipid peroxidation, increasing toxic effects in the liver and other tissues [17].…”

Section: Discussionmentioning

confidence: 99%

Acetaminophen Has Lipid Composition-Dependent Membrane Interactivity That Could Be Related to Nephrotoxicity but Not to Analgesic Activity and Hepatotoxicity

Mizogami

Tsuchiya

2022

Med Princ Pract

View full text Add to dashboard Cite

Objective: Although acetaminophen is one of the most widely used over-the-counter drugs, the mechanisms by which this classical drug exerts analgesic, hepatotoxic and nephrotoxic effects remain unclear. We hypothesized that acetaminophen might mechanistically interact with cellular membranes of nerve, liver and kidney. In order to verify this hypothesis, we studied the interactivity of acetaminophen with biomimetic lipid-bilayer membranes by comparing with its structurally-related phenacetin. Methods: Liposomal membranes were prepared with phospholipids and cholesterol to be unilamellar vesicles suspended in the buffer of pH 7.4 by mimicking the membrane lipid composition of neuronal cells, hepatocytes and nephrocytes. They were subjected to the reactions with acetaminophen and phenacetin at clinically-relevant concentrations, followed by measuring fluorescence polarization to determine their membrane interactivity to modify membrane fluidity. Results: Acetaminophen and phenacetin interacted with neuro-mimetic and hepato-mimetic membranes to increase membrane fluidity at 10–100 μM. Both drugs were more effective in fluidizing hepato-mimetic membranes than neuro-mimetic membranes. Although the membrane-interacting potency was phenacetin >> acetaminophen in neuro-mimetic and hepato-mimetic membranes, such membrane effects conflicted with their relative analgesic and hepatotoxic effects. Acetaminophen and phenacetin strongly interacted with nephro-mimetic membranes to increase membrane fluidity at 2–100 μM and 0.1–100 μM, respectively. Phenacetin interacted with nephro-mimetic membranes at 2 μM more potently than acetaminophen, which was consistent with their relative nephrotoxic effects. Conclusion: From a mechanistic point of view, the lipid composition-dependent membrane interactivity of acetaminophen correlates to nephrotoxicity but not to analgesic activity and hepatotoxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Acetaminophen Has Lipid Composition-Dependent Membrane Interactivity That Could Be Related to Nephrotoxicity but Not to Analgesic Activity and Hepatotoxicity

Mizogami

Tsuchiya

2022

Med Princ Pract

View full text Add to dashboard Cite

show abstract

“…Thus, clinical trials have suggested the usefulness of Met in the treatment of polycystic ovary syndrome, obesity, cardiovascular complications and, most importantly, in reducing the risk and mortality of cancer, especially pancreatic, liver and lung cancer [15]. In addition, several research directions have shown the protective role of Met against liver damage by toxic substances, such as acetaminophen [23] or arsenic trioxide [16], as well as in the prevention of certain liver pathologies, such as liver cirrhosis [24].…”

Section: Discussionmentioning

confidence: 99%

In Vitro and In Ovo Evaluation of the Potential Hepatoprotective Effect of Metformin

et al. 2022

View full text Add to dashboard Cite

Background and Objectives: Metformin is currently the leading drug of choice for treating type 2 diabetes mellitus, being one of the most widely used drugs worldwide. The beneficial effects of Metformin, however, extend far beyond the reduction of blood glucose. Therefore, this study aimed to evaluate Metformin’s effects both in vitro and in ovo. Materials and Methods: Metformin has been tested in five different concentrations in human hepatocytes —HepaRG, in terms of cell viability, morphology, structure and number of nuclei and mitochondria, as well as the effect on cell migration. Through the application of HET-CAM, the biocompatibility and potential anti-irritant, as well as protective effects on the vascular plexus were also assessed. Results: According to the results obtained, Metformin increases cell viability without causing morphological changes to cells, mitochondria, or nuclei. Metformin displayed an anti-irritant activity rather than causing irritation at the level of the vascular plexus. Conclusions: In conclusion, Metformin enhances cell viability and proliferation and, has a protective effect on the vascular plexus. Nonetheless, more studies are required to clarify the mechanism of hepatoprotective effect of metformin.

show abstract

“…Similarly, Atteritano et al (43) demonstrated a marked increase in the SCE frequency in the MTX group in patients with rheumatoid arthritis. Another A suggested mechanism underlying the increase in CA and SCE frequencies in cultured lymphocytes treated with MTX may involve the generation of ROS induced by MTX, which potentiate cellular damage (25). Several anticancer agents, including MTX, induce cellular genotoxicity via DNA oxidation, ROS production and reducing the total antioxidant capacity (17,44).…”

Section: Discussionmentioning

confidence: 99%

“…Cheki et al (24) reported that metformin has potential protective effects against cisplatin-induced genotoxicity in rat bone marrow cells due to its antioxidant properties. Moreover, another study demonstrated that metformin exerted protective effects against acetaminophen-induced liver toxicity by reducing overall hepatic oxidative stress (25). Thus, the present study aimed to assess the potential ameliorative effects of metformin against MTX-induced genotoxicity in cultured human lymphocytes.…”

Section: Introductionmentioning

confidence: 98%

Ameliorative effect of metformin on methotrexate-induced genotoxicity: An in vitro study in human cultured lymphocytes

et al. 2021

View full text Add to dashboard Cite

Methotrexate is a folic acid antagonist that has been shown to be genotoxic to normal healthy cells. Metformin is an insulin-sensitizing agent, with multiple potential pharmacodynamic profiles. The aim of the present study was to evaluate the genotoxic effect of methotrexate on DNA and the potential ameliorative effect of metformin on chromosomal damage induced by methotrexate. The present study was performed in vitro, and the frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in human cultured lymphocytes were measured. Blood samples from five non-smoking healthy men aged 20-35 years were donated and used in the present study. Treatment of cultured blood cells with methotrexate significantly increased the number of cells with CAs (P<0.0001) and the frequency of SCEs (P<0.0001). The chromosomal injury induced by methotrexate was significantly reduced by pretreatment of the samples with metformin (P<0.0001). Importantly, the treatment of the cells with metformin alone did not affect the frequency of SCEs compared with the control group (P>0.05). Additionally, methotrexate and metformin alone, and combined, induced significant decreases in the proliferative index compared with the control group (P<0.05). In conclusion, metformin ameliorated the genotoxicity induced by methotrexate in cultured human lymphocytes.

show abstract

Metformin ameliorates acetaminophen-induced sub-acute toxicity via antioxidant property

Cited by 26 publications

References 65 publications

Acetaminophen Has Lipid Composition-Dependent Membrane Interactivity That Could Be Related to Nephrotoxicity but Not to Analgesic Activity and Hepatotoxicity

Acetaminophen Has Lipid Composition-Dependent Membrane Interactivity That Could Be Related to Nephrotoxicity but Not to Analgesic Activity and Hepatotoxicity

In Vitro and In Ovo Evaluation of the Potential Hepatoprotective Effect of Metformin

Ameliorative effect of metformin on methotrexate-induced genotoxicity: An in vitro study in human cultured lymphocytes

Contact Info

Product

Resources

About