Publications by authors named "J Akakpo"
Article Synopsis
- Cisplatin is a highly effective chemotherapy for treating solid tumors and bladder cancer but is limited by nephrotoxicity, especially in men due to the activation of the enzyme CYP2E1.
- Recent studies show that inhibiting CYP2E1 can protect against nephrotoxicity caused by cisplatin, and the drug 4-methylpyrazole (4MP) has been identified as a potential inhibitor.
- In preclinical mouse models, 4MP treatment significantly reduced kidney damage from cisplatin, suggesting a promising avenue for reducing nephrotoxicity in clinical settings, as patients with bladder cancer do not express CYP2E1 in their cancer cells.
Liver injury caused by acetaminophen (APAP) overdose is the leading cause of acute liver failure in western countries. The mode of APAP-induced cell death has been controversially discussed with ferroptosis emerging as a more recent hypothesis. Ferroptosis is characterized by ferrous iron-catalyzed lipid peroxidation (LPO) causing cell death, which can be prevented by the lipophilic antioxidants ferrostatin-1 and UAMC-3203.
View Article and Find Full Text PDFAcetaminophen (APAP)-induced hepatotoxicity is comprised of an injury and recovery phase. While pharmacological interventions, such as N-acetylcysteine (NAC) and 4-methylpyrazole (4-MP), prevent injury there are no therapeutics that promote recovery. JNJ-26366821 (TPOm) is a novel thrombopoietin mimetic peptide with no sequence homology to endogenous thrombopoietin (TPO).
View Article and Find Full Text PDFLiver injury and acute liver failure caused by an acetaminophen (APAP) overdose is a significant clinical problem in western countries. With the introduction of the mouse model of APAP hepatotoxicity in the 1970 s, fundamental mechanisms of cell death were discovered. This included the recognition that part of the APAP dose is metabolized by cytochrome P450 generating a reactive metabolite that is detoxified by glutathione.
View Article and Find Full Text PDFAcute kidney injury (AKI) is a common complication in acetaminophen (APAP) overdose patients and can negatively impact prognosis. Unfortunately, N-acetylcysteine, which is the standard of care for the treatment of APAP hepatotoxicity does not prevent APAP-induced AKI. We have previously demonstrated the renal metabolism of APAP and identified fomepizole (4-methylpyrazole, 4MP) as a therapeutic option to prevent APAP-induced nephrotoxicity.
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