Nicotine augments glomerular injury in a rat model of acute nephritis.
OBJECTIVE
Epidemiologic studies suggest that cigarette smoke worsens the progression of renal injury in patients with glomerular diseases. The mechanisms involved have not been elucidated. These studies were designed to determine whether nicotine worsens markers of inflammation including glomerular cell proliferation and fibronectin deposition in an in vivo model of glomerular injury.


METHODS
Sprague-Dawley rats were injected with anti-Thy1 antibody and given either tap water or nicotine in the drinking water until sacrifice at day 14. Fibronectin expression was measured by Western blot and immunohistochemistry. COX-2 expression was also determined by Western blot in the kidney cortex of rats treated with nicotine and in cultured human mesangial cells treated with nicotine.


RESULTS
Anti-Thy1 antibody administration resulted in a significant increase in the number of cells per glomerulus that was further increased by the administration of nicotine. In nephritic rats, the administration of nicotine significantly increased fibronectin and COX-2 expression. In cultured human mesangial cells we also demonstrated that nicotine increases COX-2 expression and activity and that COX-2 mediates mesangial cell proliferation in response to nicotine.


CONCLUSIONS
Either in vivo or in vitro treatment with nicotine leads to activation of inflammatory mediators and hallmarks of glomerular injury, which may explain the mechanisms involved in the deleterious effects of cigarette smoking on renal disease.
VA Medical Center, Miami, Fla., USA. ejaimes@uab.edu
Edgar A
EA
Jaimes
Run-Xia
RX
Tian
Mahesh S
MS
Joshi
Leopoldo
L
Raij
D000208:Acute Disease; D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005353:Fibronectins / Q000378:metabolism; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology*; D007518:Isoantibodies / Q000494:pharmacology; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects
D005353:Fibronectins; D007518:Isoantibodies; D018722:Nicotinic Agonists; D011453:Prostaglandins; C035678:anti-Thy antibody; D009538:Nicotine; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat