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Acute kidney injury (AKI) results in significant mortality, chronic kidney disease, and numerous other complications. Additionally, AKI imposes a substantial burden on patients, societies, and healthcare systems. Unfortunately, there are currently no clinically approved pharmacotherapies for the prevention or treatment of AKI. The present management approach primarily centers on mitigating risk factors to prevent AKI and providing supportive care following its diagnosis. Tamoxifen (TAM) is the oldest and most widely prescribed selective estrogen receptor modulator for breast cancer. Our research has revealed that mice subjected to preconditioning with TAM experienced a reduced severity of AKI.
Ischemia-reperfusion injury (IRI) was employed as the AKI model. In the in vivo setting, TAM was administered prior to the onset of AKI. Renal function was assessed, and the proliferation and apoptosis of tubular cells were examined. Additionally, we delved into the impact of TAM using mouse renal proximal tubular epithelial cells (MRPTEpiC), with a particular focus on oxidative stress.
We noticed that kidneys administered with TAM displayed an early rosy appearance, indicating improved renal perfusion after IRI compared to those without TAM. Furthermore, the expression of estrogen receptor α and β on tubular cells increased after IRI-AKI. Plasma levels of blood urea nitrogen and creatinine were lower in the TAM group in comparison to the non-TAM group. Our findings also indicated that mice treated with TAM had fewer apoptotic and more proliferative tubular cells. In vitro, MRPTEpiC cells treated with TAM exhibited a higher oxygen radical absorbance capacity.
Figure. TAM reduced IRI-AKI severity and increased estrogen receptor expression on tubular cell (A) Bar charts showed the plasma levels of BUN and Cre. Data were expressed as mean + SEM. **P<0.01 (B) Representative images showed increased estrogen receptor expression on tubular cell with after TAM treatment. Original magnification, ×400.
TAM has the potential to mitigate the severity of IRI-AKI by reducing tubular cell apoptosis. Mice subjected to TAM preconditioning demonstrated increased proliferation of tubular cells, attributed to its superior antioxidative stress properties. Consequently, TAM appears to be a promising therapeutic agent for the prevention of AKI.