Journal of Clinical Toxicology
Open Access

Involvement of the transcription factors NF-kB and Nrf2 in aldosterone induced DNA damage

4^th Global Summit on Toxicology

August 24-26, 2015 Philadelphia, USA

Nicole Schupp

Posters-Accepted Abstracts: J Clin Toxicol

Abstract :

Epidemiological studies found an increased risk for kidney cancer in hypertensive patients. These patients frequently exhibit
hyperaldosteronism, known to contribute to kidney injury, with oxidative stress playing an important role. We investigated,
in vitro and in vivo; the capacity of kidney cells to upregulate transcription factors like NF-κB and Nrf2. Aldosterone activated the
pro-survival factor NF-κB in vitro and in vivo and led to the expression of anti-apoptotic proteins like Bcl-2. The NF-κB-inhibitor
PDTC reduced DNA damage in kidney cells. Further, aldosterone activated the regulator of the antioxidative defense, Nrf2 in vitro
and in vivo and increased the expression of enzymes involved in glutathione synthesis and detoxification. The activation of the two
transcription factors was mediated by the mineralocorticoid receptor (MR) and oxidative stress. In vitro, while at 24 h of aldosterone
exposure oxidant levels remained high, a decrease in Nrf2 activation, glutathione, and target gene levels was observed. Nrf2 activation
therefore could not protect cells against oxidative DNA damage, since aldosterone-induced double strand breaks and 8-oxodG lesions
steadily rose. Administration of the Nrf2 activator sulforaphane enhanced the Nrf2 response in vitro and in vivo and thereby prevented
aldosterone-induced DNA damage. Aldosterone-induced DNA damage triggers the activation of NF-κB and Nrf2. Inhibition of NF-
κB, as well as activation of Nrf2 decrease DNA damage.