Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in rats.

Rhabdomyolysis is characterized by muscle damage and leads to acute kidney injury (AKI). Clinical and experimental studies suggest that glycogen synthase kinase 3ß (GSK3ß) inhibition protects against AKI basically through its critical role in tubular epithelial cell apoptosis, inflammation and fibrosis. Treatment with a single dose of lithium, an inhibitor of GSK3ß, accelerated recovery of renal function in cisplatin and ischemic/reperfusion-induced AKI models. We aimed to evaluate the efficacy of a single dose of lithium in the treatment of rhabdomyolysis-induced AKI. Male Wistar rats were allocated to four groups: Sham, received saline 0.9% intraperitoneally (IP); lithium (Li), received a single IP injection of lithium chloride (LiCl) 80 mg/kg body weight (BW); glycerol (Gly), received a single dose of glycerol 50% 5 mL/kg BW intramuscular (IM); glycerol plus lithium (Gly+Li), received a single dose of glycerol 50% IM plus LiCl IP injected 2 hours after glycerol administration. After 24 hours, we performed inulin clearance experiments and collected blood / kidney / muscle samples. Gly rats exhibited renal function impairment accompanied by kidney injury, inflammation and alterations in signaling pathways for apoptosis and redox state balance. Gly+Li rats showed a remarkable improvement in renal function as well as kidney injury score, diminished CPK levels and an overstated decrease of renal and muscle GSK3ß protein expression. Furthermore, administration of lithium lowered the amount of macrophage infiltrate, reduced NFκB and caspase renal protein expression and increased the antioxidant component MnSOD. Lithium treatment attenuated renal dysfunction in rhabdomyolysis-associated AKI by improving inulin clearance and reducing CPK levels, inflammation, apoptosis and oxidative stress. These therapeutic effects were due to the inhibition of GSK3ß and possibly associated with a decrease in muscle injury.

The European Portuguese Posthumous Dignity Therapy Schedule of Questions: Initial development and validation.

OBJECTIVE: Dignity therapy (DT) is a brief psychotherapeutic intervention with beneficial effects in the end-of-life experience. Since it provides a continuing bond between the bereaved and their loved ones, we speculated that it could be offered as a novel bereavement intervention following the patient's death. We aimed to develop, translate, and validate the Posthumous DT Schedule of Questions (p-DT-SQ), for administration with bereaved relatives or friends. METHOD: The original DT-SQ was adapted for application with bereaved relatives or friends. It was translated and back-translated to European Portuguese and revised by an expert committee. Content validity was assessed by the Content Validity Coefficient (CVC). The instrument was tested in a sample of 50 individuals from a large Senior Residence in Lisbon (10 elderly people and 40 healthcare professionals), who assessed face validity. RESULTS: The p-DT-SQ showed very good CVC (0.94) and face validity: it was considered clear, easy to understand, reasonable in length, and not difficult to answer. Participants felt comfortable answering the p-DT-SQ and felt it could positively affect the way themselves or others would remember their loved ones, allowing an understanding of the deceased's concerns, interests, and values. SIGNIFICANCE OF RESULTS: We created and validated an adapted version of the DT-SQ to be used posthumously by bereaved family and friends. The European Portuguese version of the p-DT-SQ is clear, comprehensible, and aligned with the fundamentals of DT. While our data suggest its beneficial effects for those who are bereft, future research is needed to examine the impact of p-DT-SQ for those who are grieving.

The association between obesity and vitamin D deficiency modifies the progression of kidney disease after ischemia/reperfusion injury.

Acute kidney injury (AKI) alters renal hemodynamics, leading to tubular injury, activating pathways of inflammation, proliferation, and cell death. The initial damage caused to renal tissue after an ischemia/reperfusion (I/R) injury exerts an important role in the pathogenesis of the course of AKI, as well as in the predisposition to chronic kidney disease. Vitamin D deficiency has been considered a risk factor for kidney disease and it is associated with tubulointerstitial damage, contributing to the progression of kidney disease. Obesity is directly related to diabetes mellitus and hypertension, the main metabolic disorders responsible for the progression of kidney disease. Furthermore, the expansion of adipose tissue is described as an important factor for increased secretion of pro-inflammatory cytokines and their respective influence on the progression of kidney disease. We aimed to investigate the influence of vitamin D deficiency and obesity on the progression of renal disease in a murine model of renal I/R. Male Wistar rats underwent renal I/R surgery on day 45 and followed until day 90 of the protocol. We allocated the animals to four groups according to each diet received: standard (SD), vitamin D-depleted (VDD), high fat (HFD), or high fat vitamin D-depleted (HFDV). At the end of 90 days, we observed almost undetectable levels of vitamin D in the VDD and HFDV groups. In addition, HFD and HFDV groups presented alterations in the anthropometric and metabolic profile. The combination of vitamin D deficiency and obesity contributed to alterations of functional and hemodynamic parameters observed in the HFDV group. Moreover, this combination favored the exacerbation of the inflammatory process and the renal expression of extracellular matrix proteins and phenotypic alteration markers, resulting in an enlargement of the tubulointerstitial compartment. All these changes were associated with an increased renal expression of transforming growth factor ß and reduced expression of the vitamin D receptor. Our results show that the synergistic effect of obesity and vitamin D deficiency exacerbated the hemodynamic and morphological changes present in the evolution of renal disease induced by I/R.

Considerações sobre a experiência em uma clínica de psicanálise na rua / Considerations about the experience in a street psychoanalysis clinic

Este artigo tem como objetivo trazer considerações sobre a experiência em uma clínica de psicanálise na rua, cujo nome é “Psicanálise na Rua”, que aconteceu no transcorrer da vida urbana da cidade de Santa Maria, Rio Grande do Sul, na Praça Saldanha Marinho. Aqui se faz uma retomada na historicidade de clínicas públicas para que possamos visualizar o percurso de outras iniciativas de clínicas públicas, em espaços públicos e abertos, e assim aproximar com a nossa atual prática clínica, levantando questionamentos, aproximando teoria e prática psicanalítica de Freud e Lacan e seus interlocutores com o acontecimento da clínica na rua. Através desse construto teórico oportunizou-se pensar formas de fazer clínica psicanalítica, e a importância de atentarmos para suas singularidades, concluindo não existir a clínica psicanalítica, mas uma clínica psicanalítica em suas singularidades.(AU)

This article aims to bring considerations about the experience in a street psychoanalysis clinic, whose name is “Psychoanalysis on the Street”, which takes place in the course of urban life in the city of Santa Maria, Rio Grande do Sul, at Praça Saldanha Marinho. Here, the historicity of public clinics is taken up again so that we can visualize the course of other initiatives of public clinics, in public and open spaces, and thus bring them closer to our current clinical practice, raising questions, bringing together Freud’s theory and psychoanalytic practice and Lacan and his interlocutors with the event of the clinic in the street. Through this theoretical construct, it was possible to think about the different ways of doing a psychoanalytic clinic, and the importance of paying attention to its singularities, concluding that there is no psychoanalytic clinic, but a psychoanalytic clinic in its singularities.(AU)

Treatment with ß-blocker nebivolol ameliorates oxidative stress and endothelial dysfunction in tenofovir-induced nephrotoxicity in rats.

Background: Tenofovir disoproxil fumarate (TDF), a widely prescribed component in antiretroviral regimens, has been associated with nephrotoxicity. Nebivolol is a third generation selective ß-1 adrenergic receptor blocker and may protect renal structure and function through the suppression of oxidative stress and enhancement of nitric oxide (NO) synthesis. We aimed to investigate whether nebivolol could be an effective therapeutic strategy to mitigate tenofovir-induced nephrotoxicity. Methods: We allocated Wistar rats to four groups: control (C), received a standard diet for 30 days; NBV, received a standard diet for 30 days added with nebivolol (100 mg/kg food) in the last 15 days; TDF, received a standard diet added with tenofovir (300 mg/kg food) for 30 days; and TDF+NBV, received a standard diet added with tenofovir for 30 days and nebivolol in the last 15 days. Results: Long-term exposure to tenofovir led to impaired renal function, induced hypertension, endothelial dysfunction and oxidative stress. Nebivolol treatment partially recovered glomerular filtration rate, improved renal injury, normalized blood pressure and attenuated renal vasoconstriction. Administration of nebivolol contributed to reductions in asymmetric dimethylarginine (ADMA) levels as well as increases in endothelial nitric oxide sintase (eNOS) accompanied by renin-angiotensin-aldosterone system downregulation and decreases in macrophage and T-cells infiltrate. Furthermore, nebivolol was responsible for the maintenance of the adequate balance of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels and it was associated with reductions in NADPH oxidase (NOX) subunits. Conclusion: Nebivolol holds multifaceted actions that promote an advantageous option to slow the progression of kidney injury in tenofovir-induced nephrotoxicity.

Optimal Nitrate Supplementation in Phaeodactylum tricornutum Culture Medium Increases Biomass and Fucoxanthin Production.

Phaeodactylum tricornutum is a model diatom with numerous potential applications in the industry, including the production of high-value carotenoid pigments such as fucoxanthin. This compound is a potent antioxidant currently extracted mainly from brown macroalgae. Fucoxanthin exhibits several biological properties with well-known beneficial effects in the treatment and prevention of lifestyle-related diseases. P. tricornutum offers a valuable alternative to macroalgae for fucoxanthin production as it has a specific productivity that is 10-fold higher as compared with macroalgae. However, production processes still need to be optimised to become a cost-effective alternative. In this work, we investigated the optimal supplementation of nitrate in a cultivation medium that is currently used for P. tricornutum and how this nitrate concentration affects cell growth and fucoxanthin production. It has previously been shown that the addition of sodium nitrate increases productivity, but optimal conditions were not accurately determined. In this report, we observed that the continuous increase in nitrate concentration did not lead to an increase in biomass and fucoxanthin content, but there was rather a window of optimal values of nitrate that led to maximum growth and pigment production. These results are discussed considering both the scale up for industrial production and the profitability of the process, as well as the implications in the cell's metabolism and effects in fucoxanthin production.

Detection and Stabilization of a Previously Unknown Two-Dimensional (Pseudo)polymorph using Lateral Nanoconfinement.

We report on the detection and stabilization of a previously unknown two-dimensional (2D) pseudopolymorph of an alkoxy isophthalic acid using lateral nanoconfinement. The self-assembled molecular networks formed by the isophthalic acid derivative were studied at the interface between covalently modified graphite and an organic solvent. When self-assembled on graphite with moderate surface coverage of covalently bound aryl groups, a previously unknown metastable pseudopolymorph was detected. This pseudopolymorph, which was presumably "trapped" in between the surface bound aryl groups, underwent a time-dependent phase transition to the stable polymorph typically observed on pristine graphite. The stabilization of the pseudopolymorph was then achieved by using an alternative nanoconfinement strategy, where the domains of the pseudopolymorph could be formed and stabilized by restricting the self-assembly in nanometer-sized shallow compartments produced by STM-based nanolithography carried out on a graphite surface with a high density of covalently bound aryl groups. These experimental results are supported by molecular mechanics and molecular dynamics simulations, which not only provide important insight into the relative stabilities of the different structures, but also shed light onto the mechanism of the formation and stabilization of the pseudopolymorph under nanoscopic lateral confinement.

The Restoration of Vitamin D Levels Slows the Progression of Renal Ischemic Injury in Rats Previously Deficient in Vitamin D.

Chronic kidney disease (CKD) remains a global public health problem. The initial damage after ischemia/reperfusion (I/R) injury plays an important role in the pathogenesis of acute kidney injury (AKI) and predisposition to CKD. Several studies have been showing that nontraditional risk factors such as AKI and hypovitaminosis D could also be involved in CKD progression. Vitamin D deficiency (VDD) is associated with hemodynamic changes, activation of inflammatory pathways and renal disease progression (RDP) following I/R-AKI. Strategies for prevention and/or slowing RDP have been determined and the sufficiency of vitamin D has been emerging as a renoprotective factor in many diseases. Therefore, we investigated the effect of the restoration of vitamin D levels in the progression of I/R injury (IRI) in rats previously deficient in vitamin D. On day 30, male Wistar rats were submitted to bilateral 45 min IRI and divided into three groups: IRI, standard diet for 120 days; VDD+IRI, vitamin D-free diet for 120 days; and VDD+IRI+R, vitamin D-free diet in the first 30 days and just after I/R, we reintroduced the standard diet in the last 90 days. After the 120-day protocol, VDD+IRI+R rats presented an improvement in the renal function and renal protein handling followed by a smaller fractional interstitial area. Furthermore, those animals exhibited a reestablishment regarding the hemodynamic parameters and plasma levels of aldosterone, urea and PTH. In addition, the restoration of vitamin D levels reestablished the amount of MCP1 and the renal expressions of CD68+ and CD3+ cells in the VDD+IRI+R rats. Also, VDD+IRI+R rats showed a restoration regarding the amount of collagen type III and renal expressions of fibronectin, vimentin and α-SMA. Such changes were also accompanied by a reestablishment on the renal expression of VDR, Klotho, JG12, and TGF-ß1. Our findings indicate that the restoration of vitamin D levels not only improved the renal function and hemodynamics but also reduced the inflammation and fibrosis lesions observed in I/R-AKI associated with VDD. Thus, monitoring of vitamin D status as well as its replacement in the early stages of kidney injury may be a therapeutic alternative in the mitigation of renal disease progression.

"Truly holistic?" Differences in documenting physical and psychosocial needs and hope in Portuguese palliative patients.

OBJECTIVE: Palliative care (PC) aims to improve patients' and families' quality of life through an approach that relieves physical, psychosocial, and spiritual suffering, although the latter continues to be under-assessed and under-treated. This study aimed to describe the prevalence of physical, psychosocial, and hope assessments documented by a PC team in the first PC consultation. METHOD: The retrospective descriptive analysis of all first PC consultations registered in our anonymized database (December 2018-January 2020), searching for written documentation regarding (1) Edmonton Symptom Assessment Scale (ESAS) physical subscale (pain, tiredness, nausea, drowsiness, appetite, shortness of breath, constipation, insomnia, and well-being), (2) the single question "Are you depressed?" (SQD), (3) the question "Do you feel anxious?" (SQA), (4) feeling a burden, (5) hope-related concerns, (6) the dignity question (DQ), and (7) will to live (WtL). RESULTS: Of the 174 total of patients anonymously registered in our database, 141 PC home patients were considered for analysis; 63% were male, average age was 70 years, the majority had malignancies (82%), with a mean performance status of 52%. Evidence of written documentation was (1) ESAS pain (96%), tiredness (89%), nausea (89%), drowsiness (79%), appetite (89%), shortness of breath (82%), constipation (74%), insomnia (72%), and well-being (52%); (2) the SQD (39%); (3) the SQA (11%); (4) burden (26%); (5) hope (11%); (6) the DQ (33%); and (7) WtL (33%).Significant differences were found between the frequencies of all documented items of the ESAS physical subscale (29%), and all documented psychosocial items (SQD + SQA + burden + DQ) (1%), hope (11%), and WtL (33%) (p = 0.0000; p = 0.0005; p = 0.0181, respectively). SIGNIFICANCE OF RESULTS: There were differences between documentation of psychosocial, hope, and physical assessments after the first PC consultation, with the latter being much more frequent. Further research using multicenter data is now required to help identify barriers in assessing and documenting non-physical domains of end-of-life experience.

Acute kidney injury induced by glycerol is worsened by orchiectomy and attenuated by testosterone replacement.

Although several studies have demonstrated that the male gender represents an independent risk factor for renal disease, evidence shows that androgens exert renal protective actions. The findings are controversial and no studies have evaluated the effects of orchiectomy and testosterone replacement on glycerol-induced renal injury. Male Wistar rats were submitted to orchiectomy or sham surgery and divided into four groups: SC, sham control rats injected with NaCl; SG, sham rats injected with glycerol; OG, orchiectomized rats injected with glycerol; OGT, orchiectomized rats injected with glycerol and testosterone. Testosterone was administered daily for 14 days in the OGT group. After 11 days of testosterone replacement in the OGT group, SC rats were submitted to a saline injection, while SG, OG and OGT rats received glycerol. All rats were euthanized three days after injections. OG rats presented higher serum creatinine and urea, and sodium excretion, compared to SC and SG, while testosterone attenuated these changes. Acute tubular necrosis was also mitigated by testosterone. Renal immunostaining for macrophages, lymphocytes and NF-κB was higher in OG compared to SC and SG. In addition, renal interleukin-1ß, Caspase 3 and AT1 gene expression was higher in OG rats compared to SG. Testosterone attenuated these alterations, except the NF-κB immunostaining. The renal NO was lower in OG rats compared to SG. Only the OG rats presented decreases in serum NO and renal HO-1, and increased TNF-α, angiotensinogen and AT1 expression compared to SC. We conclude that orchiectomy worsened glycerol-induced kidney injury, while testosterone attenuated this renal damage.

The Blockade of TACE-Dependent EGF Receptor Activation by Losartan-Erlotinib Combination Attenuates Renal Fibrosis Formation in 5/6-Nephrectomized Rats Under Vitamin D Deficiency.

Chronic kidney disease (CKD) has been considered a major public health issue. In addition to cardiovascular diseases and infections, hypovitaminosis D has been considered a non-traditional aggravating factor for CKD progression. Interstitial fibrosis is a hallmark of CKD strongly correlated with deterioration of renal function. Transforming growth factor ß (TGF-ß) is the major regulatory profibrotic cytokine in CKD. Many injurious stimuli converge on the TGF-ß pathway, which has context-dependent pleiotropic effects and interacts with several related renal fibrosis formation (RFF) pathways. Epidermal growth factor receptor (EGFR) is critically involved in CKD progression, exerting a pathogenic role in RFF associated with TGF-ß-related fibrogenesis. Among others, EGFR pathway can be activated by a disintegrin and a metalloproteinase known as tumor necrosis factor α-converting enzyme (TACE). Currently no effective therapy is available to completely arrest RFF and slow the progression of CKD. Therefore, we investigated the effects of a double treatment with losartan potassium (L), an AT1R antagonist, and the tyrosine kinase inhibitor erlotinib (E) on the alternative pathway of RFF related to TACE-dependent EGFR activation in 5/6-nephrectomized rats under vitamin D deficiency (D). During the 90-day protocol, male Wistar rats under D, were submitted to 5/6 nephrectomy (N) on day 30 and randomized into four groups: N+D, no treatment; N+D+L, received losartan (50 mg/kg/day); N+D+E, received erlotinib (6 mg/kg/day); N+D+L+E received losartan+erlotinib treatment. N+D+L+E data demonstrated that the double treatment with losartan+erlotinib not only blocked the TACE-dependent EGF receptor activation but also prevented the expression of TGF-ß, protecting against RFF. This renoprotection by losartan+erlotinib was corroborated by a lower expression of ECM proteins and markers of phenotypic alteration as well as a lesser inflammatory cell infiltrate. Although erlotinib alone has been emerging as a renoprotective drug, its association with losartan should be considered as a potential therapeutic strategy on the modulation of RFF.

Vitamin D deficiency is a potential risk factor for lipid Amphotericin B nephrotoxicity.

Invasive fungal infections (IFI) is a worldwide serious health problem and Amphotericin B (AmB) has been considered the drug of choice for IFI treatment. Despite its efficacy, clinical use of AmB has been associated with renal toxicity. Some lines of evidence have shown that an extemporaneous lipid emulsion preparation of AmB (AmB/LE) was able to attenuate nephrotoxicity, presenting similar benefits at a lower cost. Studies have been demonstrating that hypovitaminosis D may hasten the progression of kidney disease and reflect on a worse prognosis in cases of drug-induced nephrotoxicity. In view of the high worldwide incidence of hypovitaminosis D, the aim of this study was to investigate whether vitamin D deficiency may induce AmB/LE-related nephrotoxicity. Wistar rats were divided into four groups: control, received a standard diet for 34 days; AmB/LE, received a standard diet for 34 days and AmB/LE (5 mg/kg/day) intraperitoneally in the last 4 days; VDD, received a vitamin D-free diet for 34 days; and VDD+AmB/LE, received a vitamin D-free diet for 34 days and AmB/LE as described. At the end of the protocol, animals were euthanized and blood, urine and renal tissue samples were collected in order to evaluate AmB/LE effects on renal function and morphology. Association of AmB/LE and vitamin D deficiency led to diminished glomerular filtration rate and increased tubular injury, evidenced by reduced renal protein expression of NaPi-IIa and TRPM6 leading to hyperphosphaturia / hypermagnesuria. VDD+AmB/LE rats also presented alterations in the PTH-Klotho-FGF-23 signaling axis, urinary concentrating defect and hypertension, probably due to an inappropriate activation of the renin-angiotensin-aldosterone system. Hence, it is important to monitor vitamin D levels in AmB/LE treated patients, since vitamin D deficiency induces AmB/LE nephrotoxicity.

Preventive effect of exercise training on diabetic kidney disease in ovariectomized rats with type 1 diabetes.

IMPACT STATEMENT: To date, no studies have been found evaluating the effects of physical exercise on renal function and structure changes in ovariectomized rats with type 1 diabetes. Therefore, this work emerges with an important tool for strengthening and expanding innovative research on exercise with potential for the prevention of renal diseases in ovariectomized diabetic rats, and future development of studies that seek to increase scientific knowledge about the beneficial effects of physical exercise on renal diseases in humans.

Phase selectivity triggered by nanoconfinement: the impact of corral dimensions.

By using a novel protocol to spatially confine molecules in well-defined small 2D areas, the so-called nanocorrals, we show using scanning tunneling microscopy (STM) how this kind of confinement affects self-assembled molecular network (SAMN) formation at a liquid-solid interface. The 2D lateral confinement, imposed by the size of the nanocorrals, has a clear impact on the phase selectivity of a molecule that can form both low-density and high-density SAMNs, the high-density phase being promoted by the confinement.

Vitamin D Deficiency Aggravates the Renal Features of Moderate Chronic Kidney Disease in 5/6 Nephrectomized Rats.

The pathogenesis of chronic kidney disease (CKD) involves a very complex interaction between hemodynamic and inflammatory processes, leading to glomerular/vascular sclerosis, and fibrosis formation with subsequent evolution to end-stage of renal disease. Despite efforts to minimize the progression of CKD, its incidence and prevalence continue to increase. Besides cardiovascular diseases and infections, several studies demonstrate that vitamin D status could be considered as a non-traditional risk factor for the progression of CKD. Therefore, we investigated the effects of vitamin D deficiency (VDD) in the course of moderate CKD in 5/6 nephrectomized rats (Nx). Adult male Wistar rats underwent Sham surgery or Nx and were subdivided into the following four groups: Sham, receiving standard diet (Sham); Sham VDD, receiving vitamin D-free diet (VDD); Nx, receiving standard diet (Nx); and VDD+Nx, receiving vitamin D-free diet (VDD+Nx). Sham or Nx surgeries were performed 30 days after standard or vitamin D-free diets administration. After validation of vitamin D depletion, we considered only Nx and VDD+Nx groups for the following studies. Sixty days after surgeries, VDD+Nx rats exhibited hypertension, a greater decline in renal function and plasma FGF-23 levels, renal hypertrophy, as well as higher plasma levels of PTH and aldosterone. In addition, those animals presented more significant chronic tubulointerstitial changes (cortical interstitial expansion/inflammation/fibrosis), higher expression of collagen IV, fibronectin and α-smooth muscle actin, and lower expressions of JG12 and M2 macrophages. Also, VDD+Nx rats had greater infiltration of inflammatory cells (M1 macrophages and T-cells). Such changes were accompanied by higher expression of TGF-ß1 and angiotensinogen and decreased expression of VDR and Klotho protein. Our observations indicate that vitamin D deficiency impairs the renal function and worsens the renovascular and morphological changes, aggravating the features of moderate CKD in 5/6 nephrectomized rats.

Biasing Enantiomorph Formation via Geometric Confinement: Nanocorrals for Chiral Induction at the Liquid-Solid Interface.

Nanocorrals created by scanning probe lithography on covalently modified graphite surfaces are used to induce a chiral bias in the enantiomorphic assembly of a prochiral molecule at the liquid/graphite interface. By controlling the orientation of the nanocorrals with respect to the underlying graphite surface, the nanocorral handedness can be freely chosen and thus a chiral bias in molecular self-assembly is created at an achiral surface solely by the scanning probe lithography process.

Previous Exercise Training Reduces Markers of Renal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Female Rats.

The aim of this study is to evaluate the effects of regular moderate exercise training initiated previously or after induction of diabetes mellitus on renal oxidative stress and inflammation in STZ-induced diabetic female rats. For this purpose, Wistar rats were divided into five groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD), trained diabetic (TD), and previously trained diabetic (PTD). Only the PTD group was submitted to treadmill running for 4 weeks previously to DM induction with streptozotocin (40 mg/kg, i.v). After confirming diabetes, the PTD, TD, and TC groups were submitted to eight weeks of exercise training. At the end of the training protocol, we evaluated the following: glycosuria, body weight gain, plasma, renal and urinary levels of nitric oxide and thiobarbituric acid reactive substances, renal glutathione, and immunolocalization of lymphocytes, macrophages, and nuclear factor-kappa B (NF-κB/p65) in the renal cortex. The results showed that exercise training reduced glycosuria, renal TBARS levels, and the number of immune cells in the renal tissue of the TD and PTD groups. Of note, only previous exercise increased weight gain and urinary/renal NO levels and reduced NF-κB (p65) immunostaining in the renal cortex of the PTD group. In conclusion, our study shows that exercise training, especially when initiated previously to diabetes induction, promotes protective effects in diabetic kidney by reduction of renal oxidative stress and inflammation markers in female Wistar rats.

Correction: Ecstasy induces reactive oxygen species, kidney water absorption and rhabdomyolysis in normal rats. Effect of N-acetylcysteine and Allopurinol in oxidative stress and muscle fiber damage.

[This corrects the article DOI: 10.1371/journal.pone.0179199.].