1. Nicotine augments glomerular injury in a rat model of acute nephritis.
- Author
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Jaimes EA, Tian RX, Joshi MS, and Raij L
- Subjects
- Acute Disease, Animals, Cell Count, Cell Division drug effects, Cyclooxygenase 2 metabolism, Disease Models, Animal, Disease Progression, Fibronectins metabolism, Glomerulonephritis metabolism, Isoantibodies pharmacology, Mesangial Cells metabolism, Prostaglandins metabolism, Rats, Rats, Sprague-Dawley, Smoking adverse effects, Glomerulonephritis pathology, Mesangial Cells drug effects, Mesangial Cells pathology, Nicotine toxicity, Nicotinic Agonists toxicity
- Abstract
Background/aims: 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., Conclusion: 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.
- Published
- 2009
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