NDLI: Up-regulation of nuclear related factor 2 (NRF2) and antioxidant responsive elements by metformin protects hepatocytes against the acetaminophen toxicity

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Up-regulation of nuclear related factor 2 (NRF2) and antioxidant responsive elements by metformin protects hepatocytes against the acetaminophen toxicity

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Toxicology Research Vol - 3 Issue - 4

Toxicology Research Vol - 3 Issue - 3

Toxicology Research Vol - 3 Issue - 2

Toxicology Research Vol - 3 Issue - 1

Toxicology Research Vol -2

Toxicology Research Vol -1

Up-regulation of nuclear related factor 2 (NRF2) and antioxidant responsive elements by metformin protects hepatocytes against the acetaminophen toxicity

Content Provider	Royal Society of Chemistry (RSC)
Author	Saraswathy, Mini Ramachandran, Rajesh
Copyright Year	2014
Abstract	The inadequacy to replace acetaminophen (APAP) with a more effective analgesic continues its use in therapeutic interventions, upholding the risk of hepatotoxicity. Depletion of glutathione reserves by a metabolic intermediate of acetaminophen, N-acetyl-p-benzoquinone imine (NAPQI), is the major reason. The current study presents the combinatorial effect of metformin, a biguanide, in ameliorating the APAP toxicity. HepG2 cells were used for in vitro studies and MTT and LDH leakage assays were used for viability assessment. 10 μM of metformin improved the cell viability and membrane integrity of cells treated with a high concentration (20 mM) of acetaminophen. Intracellular antioxidant enzymes and reduced glutathione were significantly increased in cells co-administrated with metformin and acetaminophen. A decrease in apoptosis induction and ROS generation was evident by fluorescent microscopy analysis. Flow cytometry showed a quantitative improvement in cell viability. RT–PCR analysis showed an increased expression of Nrf2 genes along with inhibition of BACH 1 in cells treated with metformin and acetaminophen. The expression of the genes encoding antioxidant responsive elements such as glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione cysteine synthase (GCS) was exponentially increased which possibly leads to increased glutathione synthesis and hepatoprotection. Overall results provide new insights regarding pharmacological potential of metformin as a hepatoprotective agent against the toxicity of acetaminophen.
Starting Page	350
Ending Page	358
Page Count	9
File Format	HTM / HTML PDF
ISSN	2045452X
Volume Number	3
Issue Number	5
Journal	Toxicology Research
DOI	10.1039/c4tx00032c
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	APAP Metabolic intermediate Glutathione peroxidase Flow cytometry Reactive oxygen species Hepatoprotection Lactate dehydrogenase MTT Antioxidant LDH Paracetamol Analgesic Microscopy Glutathione reductase Cysteine synthase BACH Metformin Biguanide NAPQI Combinatorics Hepatotoxicity Glutathione Apoptosis NFE2L2
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Toxicology

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