Nicotine worsens the severity of nephropathy in diabetic mice: Implications for the progression of kidney disease in smokers

Ping Hua, Wenguang Feng, Shaonin Ji, Leopoldo Raij, Edgar A. Jaimes

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Epidemiological studies have established the role of cigarette smoking as a risk factor in the progression of chronic kidney disease, including diabetic nephropathy. We have previously reported that nicotine promotes mesangial cell proliferation and hypertrophy via activation of nonneuronal nicotinic acetylcholine receptors and that nicotine worsens renal injury in a model of acute glomerulonephritis (Jaimes E, Tian RX, Raij L. Am J Physiol Heart Circ Physiol 292: H76-H82, 2007; Jaimes EA, Tian RX, Joshi M, Raij L. Am J Nephrol 29: 319-326, 2009). These studies were designed to test the hypothesis that nicotine worsens renal injury in db/db mice, a well-established model of diabetic nephropathy, and that reactive oxygen species play an important as mediators of these effects. For these studies, nicotine (100 μg/ml) was administered in the drinking water to control and db/db mice for 10 wk. Blood pressure was measured by the tail-cuff method, and urine was collected for proteinuria. At death, kidneys were collected for histology and molecular biology. The administration of nicotine did not result in significant changes in blood pressure or blood glucose and resulted in cotinine levels similar to those found in the plasma of smokers. In diabetic mice, the administration of nicotine significantly increased urinary protein excretion (1-fold), glomerular hypertrophy, and mesangial area (∼20%). These changes were accompanied by significant increases in NADPH oxidase 4 (∼30%) and increased nitrotyrosine and Akt expression. In vitro, we determined that nicotine has additive effects to high glucose on reactive oxygen species generation and Akt phosphorylation in human mesangial cells. These findings unveil novel mechanisms that may result in the development of novel strategies in the treatment and prevention of diabetic nephropathy in smokers.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume299
Issue number4
DOIs
StatePublished - Oct 1 2010

Fingerprint

Kidney Diseases
Diabetic Nephropathies
Nicotine
Mesangial Cells
Kidney
Hypertrophy
Reactive Oxygen Species
Blood Pressure
Cotinine
NADPH Oxidase
Wounds and Injuries
Nicotinic Receptors
Glomerulonephritis
Chronic Renal Insufficiency
Proteinuria
Drinking Water
Blood Glucose
Tail
Epidemiologic Studies
Molecular Biology

Keywords

  • Reactive oxygen species
  • Tobacco

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Nicotine worsens the severity of nephropathy in diabetic mice : Implications for the progression of kidney disease in smokers. / Hua, Ping; Feng, Wenguang; Ji, Shaonin; Raij, Leopoldo; Jaimes, Edgar A.

In: American Journal of Physiology - Renal Physiology, Vol. 299, No. 4, 01.10.2010.

Research output: Contribution to journalArticle

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