Erythropoietin mitigated thioacetamide-induced renal injury via JAK2/STAT5 and AMPK pathway

Abstract

The kidney flushes out toxic substances and metabolic waste products, and homeostasis is maintained owing to the kidney efforts. Unfortunately, kidney disease is one of the illnesses with a poor prognosis and a high death rate. The current investigation was set out to assess erythropoietin (EPO) potential therapeutic benefits against thioacetamide (TAA)-induced kidney injury in rats. EPO treatment improved kidney functions, ameliorated serum urea, creatinine, and malondialdehyde, increased renal levels of reduced glutathione, and slowed the rise of JAK2, STAT5, AMPK, and their phosphorylated forms induced by TAA. EPO treatment also greatly suppressed JAK2, Phosphatidylinositol 3-kinases, and The Protein Kinase R-like ER Kinase gene expressions and mitigated the histopathological alterations brought on by TAA toxicity. EPO antioxidant and anti-inflammatory properties protected TAA-damaged kidneys. EPO regulates AMPK, JAK2/STAT5, and pro-inflammatory mediator synthesis.

Nrf2/HO‐1, NF‐κB and PI3K/Akt signalling pathways decipher the therapeutic mechanism of pitavastatin in early phase liver fibrosis in rats

“…This could be attributed to inherent individual variability in the degree of lipid peroxidation induced by TAA administration. Importantly, despite the variability, pitavastatin treatment at both doses still significantly reduced MDA levels compared to the TAA group 35,37,50,51 . The lack of dose‐dependent difference in MDA suppression between the two pitavastatin doses could suggest a potential ceiling effect on lipid peroxidation inhibition even at the lower 0.4 mg/kg dose.…”

“…Moreover, it provided a reliable means to histologically induce substantial bridging fibrosis while mitigating the risk of increased animal mortality associated with more prolonged exposures. This model was studied previously in studies 27,37,50,51,60 …”

“…Importantly, despite the variability, pitavastatin treatment at both doses still significantly reduced MDA levels compared to the TAA group. 35 , 37 , 50 , 51 The lack of dose‐dependent difference in MDA suppression between the two pitavastatin doses could suggest a potential ceiling effect on lipid peroxidation inhibition even at the lower 0.4 mg/kg dose. However, further studies with larger sample sizes may be warranted to fully evaluate the dose–response relationship.…”

Renoprotective Effect of Pitavastatin against TAA-Induced Renal Injury: Involvement of the miR-93/PTEN/AKT/mTOR Pathway

“…TAA is converted in vivo to the free radical derivatives TAA sulfoxide and TAA-S, Sdioxide. Tis causes enhanced lipid peroxidation, which leads to the generation of reactive oxygen species (ROS), which causes damage to the liver [38][39][40][41]. Te metabolites produced can afect amine lipids and proteins, increasing systemic oxidative stress, releasing cytokines, and altering kidney function since they are dispersed laterally throughout various organs, including the liver, kidney, adrenals, bone marrow, and other tissues [42][43][44].…”