Metformin Protects Against Thioacetamide Induced Liver injury in Rats

Abstract

Potent heptatotoxic chemicals such as carbon tetrachloride and thioacetamide (TAA) are used to evaluate hepatoprotective agents. Here we sought to investigate the potential protective effect of the antidiabetic and antioxidant drug, metformin against liver injury induced by TAA. Model group rats received several injections of TAA (200 mg/kg) before being sacrificed after 10 weeks and the protective group started the treatment two weeks prior to TAA injections and continued receiving both agents, metformin and TAA until the end of the experiment, week 10. Harvested liver tissues were examined using light microscopy and liver homogenates were assayed for oxidative and anti-oxidative stress markers that are known to be modulated in liver injury. Profound damage in the hepatic tissue of the model group such as liver fibrosis and destruction of hepatic architectures were revealed, which were protected by metformin comparable to the control group. TAA augmented the oxidative stress biomarker, malondialdehyde (MDA) and ameliorated the antioxidant superoxide dismutase (SOD), which were significantly (p<0.05) protected by metformin treatment. These results indicate that metformin effectively protects against TAA-induced hepatotoxicity in a rat model.

Gallic acid and metformin co-administration reduce oxidative stress, apoptosis and inflammation via Fas/caspase-3 and NF-κB signaling pathways in thioacetamide-induced acute hepatic encephalopathy in rats

“…Additionally, TAA-induced intoxication caused innate antioxidant system impairment, as evidenced by a marked consumption of both brain and liver GSH content while an increase in their MDA content. This observation is in agreement with many earlier studies which proved the TAA-induced lipid peroxidation and oxidative stress effect [ 18 , 32 , 37 ]. In harmony with the current results, a previous study suggested that reactive oxygen species (ROS) produced by TAA induce inflammation via the activation of Nuclear factor kappa B (NF-κB), which subsequently increased the release of downstream proinflammatory mediators such as IL-6 and TNF-α [ 34 ].…”

“…Likewise, Met, an inexpensive and broadly available medicine, has been shown to protect hepatocytes from oxidative stress-induced apoptosis in previous research [ 18 ]. Our study findings agree with previous data and also found that Met significantly decreased AST, ALT, ALP, GGT, total bilirubin, and direct bilirubin levels [ 47 ].…”

“…Animals in the (GA + TAA) group received a daily oral dose of GA (100 mg/kg/day) [ 7 ] and a single TAA dose on the 25th day. Animals in the (Met + TAA) group were given a daily oral dose of Met (200 mg/kg/day) [ 18 ] and a single TAA dose on the 25th day. (GA + Met + TAA) group: animals received a daily oral dose of both GA and Met (the same doses as before)) and single TAA dose on the 25th day.…”

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

“…Among the best known substances with hepatotoxic effects are acetaminophen and ethanol [15]. There are studies that show the role of Met in the prevention of liver damage associated with the consumption of toxic substances [16][17][18].…”