Fenofibrate Prevents nicotine-induced Acute Kidney Injury: Possible Involvement of Endothelial Nitric Oxide Synthase.

OBJECTIVE

The present study investigated the possible effect of fenofibrate (peroxisome proliferator-activated receptors-α agonist) in nicotine-induced acute kidney injury (AKI) in rats.

MATERIALS AND METHODS

Nicotine (2 mg/kg/day, intraperitoneally) was administered for 4 weeks to induce AKI in rats. Lipid profile and renal oxidative stress were measured and expression of mRNA for eNOS was assessed using reverse transcription-polymerase chain reaction along with serum and renal tissue nitrite levels. Serum creatinine, blood urea nitrogen and microproteinuria were estimated along with the kidney histology, as markers of kidney function. Treatment with fenofibrate (30 mg/kg per oral, 4 weeks) was initiated 3 days before the administration of nicotine and continued for 4 weeks from the day of administration of nicotine.

RESULTS

Nicotine administered rats developed apparent AKI confirmed by elevated markers of kidney function and noticeable glomerulosclerosis and tubular cell degeneration. Nicotine decreases the expression of mRNA for eNOS, along with serum and renal tissue nitrite levels. In addition, nicotine showed significantly lipid alteration beside decrease oxidative stress, assessed in terms of increase in serum thiobarbituric acid reactive substance and a marked decrease in tissue reduced glutathione. However, fenofibrate significantly prevented the development of nicotine-AKI by reducing serum creatinine, BUN, and urinary protein, normalizing the lipid profile, reducing renal oxidative stress, increases the eNOS expression and concentration of serum and renal nitrate levels.

CONCLUSION

Fenofibrate attenuates nicotine-induced AKI, via its antihyperlipidemic and antioxidant property. Moreover, fenofibrate induced upregulation of eNOS expression additionally play key roles in the improvement of nicotine-induced AKI could be the future alternative.