Apoptosis modulated by oxidative stress and inflammation during obstructive nephropathy

WALTER MANUCHA; PATRICIA G. VALLES

Inflammation & Allergy - Drug Targets

Bentham Science Publishers

Lugar: San Francisco, CA; Año: 2012 vol. 11 p. 303 - 312

1871-5281

Kidney apoptosis and fibrosis are an inevitable outcome of all kinds of progressive chronic kidney disease where congenital obstructive nephropathy is the primary cause of end-stage renal disease in children, and is also a major cause of renal failure in adults. The injured tubular cells linked to interstitial macrophages, and myofibroblasts produce cytokines and growth factors that promote an inflammatory state in the kidney, induce tubular cell apoptosis, and facilitate the accumulation of extracellular matrix. Angiotensin II plays a central role in the renal fibrogenesis at a very early stage leading to a rapid progression in chronic kidney disease. The increasing levels of angiotensin II induce pro-inflammatory cytokines, NF-êB activation, adhesion molecules, chemokines, growth factors, and oxidative stress. Furthermore, growing evidences report that angiotensin II (a pro-inflammatory hormone) increases mitochondrial oxidative stress regulating apoptosis induction. In addition, direct and indirect renin-angiotensin system blockade produce similar changes on these oxidative inflammatory disorders. Finally, this review summarizes our understanding about possible mechanisms that contribute with apoptosis modulated by inflammation and/or oxidative stress during obstructive nephropathy. The new concept of anti-inflammatory tools regulating mitochondrial oxidative stress will directly affect the inflammatory process and apoptosis. This idea could have attractive consequences in the treatment of renal and other inflammatory pathologies.