Leptin, a circulating hormone secreted mainly from adipose tissues, possesses 
protective effects on many cell types. Serum leptin concentration increases in 
patients with chronic renal failure and those undergoing maintenance dialysis. 
Gentamicin, a widely used antibiotic for the treatment of bacterial infection, 
can cause nephrotoxicity. In the present study, we intended to investigate the 
influence of leptin on apoptotic pathways and its mechanism in rat renal tubular 
cells treated with gentamicin. By using Annexin V-FITC/propidium iodide double 
staining, we found that leptin expressed a dose-dependent protective effect 
against gentamicin-induced apoptosis in rat renal tubular cells (NRK-52E) within 
24h. Pretreatment of the cells with 50 or 100 ng/ml of leptin induced Bcl-2 and 
Bcl-x(L), increased the phosphorylation of Bad, and decreased the cleaved 
caspase-3 and caspase-9 in gentamicin-treated NRK-52E cells. Leptin also 
suppressed the activation of the transcription factor NF-κB and upregulated Akt 
activation in gentamicin-treated NRK-52E cells. We found that leptin activated 
the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling 
pathway as demonstrated by the suppression of the anti-apoptotic effect of 
leptin by wortmannin. The treatment of wortmannin suppressed the leptin-induced 
phospho-Akt, Bcl-2, phospho-Bad as well as Bcl-x(L), and recovered the 
leptin-reduced cleaved caspase-3 and caspase-9. Based on our results, we 
suggested that leptin can attenuate gentamicin-induced apoptotic injury in rat 
renal tubular cells through PI3K/Akt signaling pathway.