title: Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice.
abstract: 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.
authors: Department of Forensic Pathology, University of Foggia, Foggia, Italy.
authors: Irene
authors: I
authors: Riezzo
authors: Department of Forensic Pathology, University of Foggia, Foggia, Italy.
authors: Emanuela
authors: E
authors: Turillazzi
authors: Department of Forensic Pathology, University of Foggia, Foggia, Italy.
authors: Stefania
authors: S
authors: Bello
authors: Department of Forensic Pathology, University of Foggia, Foggia, Italy.
authors: Santina
authors: S
authors: Cantatore
authors: Pharmacology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors: Daniela
authors: D
authors: Cerretani
authors: Department of Forensic Pathology, University of Pisa, Pisa, Italy.
authors: Marco
authors: M
authors: Di Paolo
authors: Pharmacology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors: Anna Ida
authors: AI
authors: Fiaschi
authors: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, University of Rome Sapienza, Viale Regina Elena 336, 00161 Rome, Italy.
authors: Paola
authors: P
authors: Frati
authors: Department of Forensic Pathology, University of Foggia, Foggia, Italy.
authors: Margherita
authors: M
authors: Neri
authors: Department of Forensic Pathology, University of Pisa, Pisa, Italy.
authors: Monica
authors: M
authors: Pedretti
authors: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, University of Rome Sapienza, Viale Regina Elena 336, 00161 Rome, Italy. Electronic address: vfinesc@tin.it.
authors: Vittorio
authors: V
authors: Fineschi
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009277:Nandrolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D000077603:Nandrolone Decanoate; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D009277:Nandrolone; D000077603:Nandrolone Decanoate
keywords: Anabolic–androgenic steroid; Apoptosis; Glutathione peroxidase; Lipoperoxidation; Malondialdehyde; Nephrotoxicity