The contralateral kidney presents with impaired mitochondrial functions and disrupted redox homeostasis after 14 days of unilateral ureteral obstruction in mice.

In unilateral ureteral obstruction (UUO), both oxidative stress and mitochondrial dysfunction are related to cell death. The aim of this study has been to characterize profiles of enzyme antioxidant activities and mitochondrial functioning of the contralateral (CL) compared to UUO and Sham (false-operated) kidneys of Balb/c mice. Kidneys were resected 14 days after obstruction for immunohistochemical and cortical mitochondrial functioning assays. Antioxidant enzymes activities were investigated in mitochondria and cytosol. Oxygen consumption (QO2) and formation of O2 reactive species (ROS) were assessed with pyruvate plus malate or succinate as the respiratory substrates. QO2 decreased in CL and UUO in all states using substrates for complex II, whereas it was affected only in UUO when substrates for complex I were used. Progressive decrease in mitochondrial ROS formation-in the forward and reverse pathway at complex I-correlates well with the inhibition of QO2 and, therefore, with decreased electron transfer at the level of complexes upstream of cytochrome c oxidase. CL and UUO transmembrane potential responses to ADP were impaired with succinate. Intense Ca2+-induced swelling was elicited in CL and UUO mitochondria. Important and selective differences exist in CL antioxidant enzymes with respect to either Sham or UUO kidneys: CL kidneys had increased mitochondrial glutathione peroxidase and cytosolic catalase activities, indicative of compensatory responses in the face of an early altered ROS homeostasis (as detected by 4-hydroxynonenal), and of a significant tendency to apoptosis. In CL and UUO, upregulation of nuclear (erythroid-derived 2)-like 2 transcription factor (Nrf2), as well as of cytoplasmic and nuclear Kelch-like ECH-associated protein 1 (Keap1) in opposition to decreased heme oxygenase-1 (HO-1), suggest impairment of the Nrf2/Keap1/HO-1 system. It is concluded that chronic obstruction impairs mitochondrial function in CL and UUO, preferentially affecting complex II.

The anabolic androgenic steroid nandrolone decanoate disrupts redox homeostasis in liver, heart and kidney of male Wistar rats.

The abuse of anabolic androgenic steroids (AAS) may cause side effects in several tissues. Oxidative stress is linked to the pathophysiology of most of these alterations, being involved in fibrosis, cellular proliferation, tumorigenesis, amongst others. Thus, the aim of this study was to determine the impact of supraphysiological doses of nandrolone decanoate (DECA) on the redox balance of liver, heart and kidney. Wistar male rats were treated with intramuscular injections of vehicle or DECA (1 mg.100 g(-1) body weight) once a week for 8 weeks. The activity and mRNA levels of NADPH Oxidase (NOX), and the activity of catalase, glutathione peroxidase (GPx) and total superoxide dismutase (SOD), as well as the reduced thiol and carbonyl residue proteins, were measured in liver, heart and kidney. DECA treatment increased NOX activity in heart and liver, but NOX2 mRNA levels were only increased in heart. Liver catalase and SOD activities were decreased in the DECA-treated group, but only catalase activity was decreased in the kidney. No differences were detected in GPx activity. Thiol residues were decreased in the liver and kidney of treated animals in comparison to the control group, while carbonyl residues were increased in the kidney after the treatment. Taken together, our results show that chronically administered DECA is able to disrupt the cellular redox balance, leading to an oxidative stress state.

Nandrolone decanoate inhibits gluconeogenesis and decreases fasting glucose in Wistar male rats.

The use of anabolic-androgenic steroids to improve physical performance or appearance has increased notably. The doses used are 10- to 100- fold higher than the therapeutic dose (TD), and this abuse can cause several side effects. Glucose metabolism is significantly affected by anabolic-androgenic steroid abuse, but studies about glycemic regulation during fasting are scarce. There are some evidences showing that testosterone can antagonize glucocorticoids action, which are crucial to glucose production during fasting. Thus, the aim of this study was to determine the impact of supraphysiological doses (SDs) of nandrolone decanoate (DECA) on rat glucose metabolism during fasting. Male Wistar rats were treated with i.m. injections of vehicle, a low TD (0.016 mg/100 g b.w.-TD group) or a high SD (1 mg/100 g b.w.-SD group) of DECA, once a week for 8 weeks. After 12 h fasting, we evaluated glucose and pyruvate tolerance tests, liver glycogen content, serum levels of gluconeogenic substrates, insulin and corticosterone, glucose uptake and hexokinase (HK) activity in skeletal muscle, and the adrenal catecholamine content. SD group had increased serum insulin levels and a blunted response to insulin regarding glucose uptake in skeletal muscle. Fasting serum glucose decreased significantly in SD group, as well as the pyruvate tolerance test and liver glycogen content. Moreover, serum levels of glycerol were increased in SD group. Our data indicate that SDs of DECA exert effects on different regulatory points of glucose metabolism, resulting in defective gluconeogenesis and decreased skeletal muscle glucose uptake in response to insulin.

The prostate after administration of anabolic androgenic steroids: a morphometrical study in rats.

PURPOSE: Many adverse effects have been associated with abuse of anabolic-androgenic steroids (AAS), including disorders of the urogenital tract. The objective of this study is to analyze the morphological modifications in the prostate ventral lobe of pubertal and adult rats chronically treated with AAS, using morphometric methods. MATERIALS AND METHODS: We studied 39 male Wistar rats weighing between 400 g and 550 g. The rats were divided into four groups: (a) control rats, with 105 days of age (C105) (n = 7); (b) control rats with 65 days of age (C65) (n = 9), injected only with the vehicle (peanut oil); (c) treated rats, with 105 days of age (T105) (n = 10) and (d) treated rats with 65 days of age (T65) (n = 13). The treated rats were injected with nandrolone decanoate at a dose of 10 mg.Kg-1 body weight. The steroid hormone and the vehicle were administered by intramuscular injection once a week for eight weeks. The rats were killed at 161 days of age (C105 and T105) and 121 days of age (C65 and T65) and the ventral prostate lobe was dissected and processed for histology. The height of the acinar epithelium, the surface densities of the lumen, epithelium and stroma were observed with X400 magnification using an Olympus light microscope coupled to a Sony CCD video camera, and the images transferred to a Sony monitor KX14-CP1. The selected histological areas were then quantified using the M42 test-grid system on the digitized fields. The data were analyzed with the Graphpad software. To compare the quantitative data in both groups (controls and treated) and the outcomes, Student's t-test was used (p < 0.05 was considered significant). RESULTS: The weight (p < 0.001) and volume (p = 0.004) of the prostate ventral lobe showed differences between C65 and T65 groups and between C105 and T105 groups. The epithelium height showed no difference between groups C65 and T65 (p = 0.8509), but the T105 group showed an increase of 32% compared to C105 (p = 0.0089). Concerning the lumen, surface density presented no difference between C65 and T65 (p = 0.9031) and a decrease of 19% for T105 compared to C105 (p = 0.0061). There was no difference in epithelium surface density between C65 and T65 (p = 0.7375), but it was 51% higher (p = 0.0065) in T105 compared with C105. Regarding stroma surface density, there were no differences between C65 and T65 or between C105 and T105. Finally, there was no difference in collagen pattern between C105 and T105, but T65 showed a predominance of collagen fibers compared to C65. CONCLUSION: The use of anabolic androgenic steroids in rats promotes structural changes in the prostate. We observed structural changes in the weight, volume and epithelium height of the prostate ventral lobe and a predominance of collagen fibers.

The prostate after administration of anabolic androgenic steroids: a morphometrical study in rats

Purpose Many adverse effects have been associated with abuse of anabolic-androgenic steroids (AAS), including disorders of the urogenital tract. The objective of this study is to analyze the morphological modifications in the prostate ventral lobe of pubertal and adult rats chronically treated with AAS, using morphometric methods. Materials and Methods: We studied 39 male Wistar rats weighing between 400 g and 550 g. The rats were divided into four groups: (a) control rats, with 105 days of age (C105) (n = 7); (b) control rats with 65 days of age (C65) (n = 9), injected only with the vehicle (peanut oil); (c) treated rats, with 105 days of age (T105) (n = 10) and (d) treated rats with 65 days of age (T65) (n = 13). The treated rats were injected with nandrolone decanoate at a dose of 10 mg.Kg-1 body weight. The steroid hormone and the vehicle were administered by intramuscular injection once a week for eight weeks. The rats were killed at 161 days of age (C105 and T105) and 121 days of age (C65 and T65) and the ventral prostate lobe was dissected and processed for histology. The height of the acinar epithelium, the surface densities of the lumen, epithelium and stroma were observed with X400 magnification using an Olympus light microscope coupled to a Sony CCD video camera, and the images transferred to a Sony monitor KX14-CP1. The selected histological areas were then quantified using the M42 test-grid system on the digitized fields. The data were analyzed with the Graphpad software. To compare the quantitative data in both groups (controls and treated) and the outcomes, Student's t-test was used (p < 0.05 was considered significant). Results: The weight (p < 0.001) and volume (p = 0.004) of the prostate ventral lobe showed differences between C65 and T65 groups and between C105 and T105 groups. The epithelium height showed no difference between groups C65 and T65 (p = 0.8509), but the T105 group showed an increase of 32% compared ...