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Alogliptin: a novel approach against cyclophosphamide-induced hepatic injury via modulating SIRT1/FoxO1 pathway. | LitMetric

AI Article Synopsis

  • Cyclophosphamide (CP) is a powerful chemotherapy drug used to treat cancer and other conditions but can cause significant liver damage (hepatotoxicity) due to oxidative stress and cell death.
  • The study explored the potential protective effects of alogliptin (Alo), a DPP-IV inhibitor, on liver injury caused by CP, focusing on its ability to enhance the PI3K/Akt/SIRT1 signaling pathway.
  • Results showed that Alo significantly reduced liver damage by lowering liver enzyme levels, increasing protective proteins, and reducing apoptosis, indicating its promise as a treatment to mitigate chemotherapy-induced liver injury.

Article Abstract

Cyclophosphamide (CP) is one of the most potent alkylating agents and is widely used in the treatment of numerous neoplastic conditions, autoimmune diseases and following organ transplantation. Due to its ability to induce oxidative stress and subsequent apoptosis, CP is affiliated with many adverse effects with special emphasis on the highly prevalent hepatotoxicity. Dipeptidyl peptidase 4 (DDP-IV) inhibitors are being rediscovered for new biological effects due to their ability to target multiple pathways, among which is the phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) axis. This could offer protection to multiple organs against reactive oxygen species (ROS) through modulating sirtuin 1 (SIRT1) expression and, in turn, inactivation of forkhead box transcription factor of the O class 1 (FoxO1), thus inhibiting apoptosis. Accordingly, the current study aimed to investigate the potential therapeutic benefit of alogliptin (Alo), a DPP-IV inhibitor, against CP-induced hepatotoxicity through enhancing PI3K/Akt/SIRT1 pathway. Forty male Wistar rats were randomly divided into four groups. The CP-treated group received a single dose of CP (200 mg/kg; i.p.). The Alo-treated group received Alo (20 mg/kg; p.o.) for 7 days with single CP injection on Day 2. Alo successfully reduced hepatic injury as witnessed through decreased liver function enzymes, increased phospho (p)-PI3K, p-Akt, superoxide dismutase (SOD) levels, SIRT1 expression, p-FoxO1 and anti-apoptotic B-cell lymphoma 2 (Bcl-2). This resulted in decreased apoptosis, as witnessed through decreased caspase-3 levels and improved histopathological picture. In conclusion, the current study succeeded to elaborate, for the first time, the promising impact of Alo in ameliorating chemotherapy-induced liver injury.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467234PMC
http://dx.doi.org/10.1093/toxres/tfaa059DOI Listing

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