Metformin Inhibits ROS/TNF-α Axis-Mediated Chronic Kidney Disease Induced by TA A Independent of Leukocyte Infiltration in Association with the Inhibition of Kidney Injury Biomarkers

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Fahaid Al-Hashem


The toxic effects of thioacetamide (TAA) and carbon tetrachloride on the human body are well recognized. In this study, we examined whether TAA intoxication can induce kidney leukocyte infiltration (measured as leukocyte common antigen CD45) associated with the augmentation of the reactive oxygen species (ROS)/tumor necrosis factor-alpha (TNF-α) axis, as well as biomarkers of kidney injury with and without metformin treatment. Rats were either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed after 10 weeks (experimental group) or were pre-treated with metformin (200 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment, at week 10 (protective group). Using basic histology staining, immunohistochemistry methods, and blood chemistry analysis, we observed profound kidney tissue injury such as glomerular and tubular damage in the experimental group, which were substantially ameliorated by metformin. Metformin also significantly (p<0.05) inhibited TAA-induced ROS, TNF-α, urea, and creatinine in harvested kidney homogenates and blood samples. In addition, a significant (p<0.0001) positive correlation between kidney tubular epithelial cell injury and the serum levels of biomarkers of oxidative stress, inflammation, and kidney injury was observed. However, TAA caused no significant (p>0.05) increase in kidney expression of CD45 positive immunostaining cells. In conclusion, we found that TAA induces kidney injury in association with the augmentation of ROS/TNF-α axis, independent of leukocyte infiltration, which is protected by metformin.

KEY WORDS: Thioacetamide; Kidney injury; ROS; Inflammation; CD45; Metformin.

How to cite this article

AL-HASHEM, F. Metformin Inhibits ROS/TNF-α axis-mediated chronic kidney disease induced by TAA independent of leukocyte infiltration in association with the inhibition of kidney injury biomarkers. Int. J. Morphol., 41(4):1191-1197, 2023.