Pyrazinamide enhances lipid peroxidation and antioxidant levels to induce liver injury in rat models through PI3k/Akt inhibition.
Abstract
Pyrazinamide (PZA) is an anti-tuberculosis drug known to causes liver injury. phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling protects against liver injury by promoting cellular antioxidant defenses and reducing intracellular reactive oxygen species (ROS) and lipid peroxidation. The regulatory mechanisms and functions of PI3K/Akt signaling during the hepatotoxicity of PZA are however not fully understood. Rats were administered PZA or/and the PI3K activator (740Y-P) for 7 days. The levels of serum parameters were examined via standard enzymatic techniques and the pathological status of the liver was confirmed by H & E staining. The levels of lipid peroxidation and antioxidant production were determined using commercial kits. Liver apoptosis was assessed by TUNEL staining. The expression of apoptosis-related proteins and PI3K/Akt signaling were assessed by western blot analysis. PZA treatment significantly increased serum alanine transaminase, aspartate transaminase, gamma-glutamyl transpeptidase and tall bilirubin leading to liver damage in rats. PZA also facilitated lipid peroxidation and suppressed antioxidant defenses. PZA led to apoptotic induction in rat liver cells through the downregulation of Bcl-2 a...Continue Reading
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