Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice.

Irene Riezzo, Emanuela Turillazzi, Stefania Bello, Santina Cantatore, Daniela Cerretani, Marco Di Paolo, Anna Ida Fiaschi, Paola Frati, Margherita Neri, Monica Pedretti, Vittorio Fineschi

Toxicology and applied pharmacology 2014 Oct 1

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Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

Citation

Irene Riezzo, Emanuela Turillazzi, Stefania Bello, Santina Cantatore, Daniela Cerretani, Marco Di Paolo, Anna Ida Fiaschi, Paola Frati, Margherita Neri, Monica Pedretti, Vittorio Fineschi. Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice. Toxicology and applied pharmacology. 2014 Oct 1;280(1):97-106