Chronic exposure to low doses of lead results in renal infiltration of immune cells, NF-kappaB activation, and overexpression of tubulointerstitial angiotensin II.
Chronic exposure to low doses of lead results in generation of reactive oxygen species, reduced nitric oxide availability, and arterial hypertension. The present studies were done to define if other conditions associated with oxidative stress, such as renal interstitial inflammation, nuclear factor-kappaB (NF-kappaB) activation, and cells expressing angiotensin II, are, in fact, features of low-dose lead exposure. Male Sprague-Dawley rats were randomly assigned to the lead group (n = 8) or the control group (n = 9). The lead group received 100 ppm lead acetate in the drinking water for 14 weeks. At the end of this period of time, rats were killed under general anesthesia, and the kidneys were harvested for studies. The lead-exposed group presented focal tubulointerstitial damage and highly significant increments in nitrotyrosine immune staining, lymphocyte and macrophage infiltration, angiotensin II-positive cells, and intranuclear positive staining for the p65 DNA-binding subunit of NF-kappaB in tubulointerstitial cells. Tubulointerstitial inflammation, cells expressing angiotensin II, and NF-kappaB activation are consequences of a 3-month low-dose exposure to lead and likely play a role in the development of hypertension and chronic lead nephropathy.
Rodríguez-Iturbe
Bernardo
B
Servicio de Nefrología, Hospital Universitario, Universidad del Zulia, Maracaibo, Venezuela. bernardori@telcel.net.ve
Sindhu
Ram K
RK
Quiroz
Yasmir
Y
Vaziri
Nosratola D
ND
D000804:Angiotensin II / Q000096:biosynthesis*; D000818:Animals; D007150:Immunohistochemistry; D007249:Inflammation; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007854:Lead / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009942:Organometallic Compounds / Q000633:toxicity*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism*
D016328:NF-kappa B; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D000804:Angiotensin II; D007854:Lead; D009569:Nitric Oxide; C008261:lead acetate