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Objectives: N-acetylcysteine (NAC) is used in Sjögren's disease (SjD) based on limited evidence. The aim of this study was to assess the efficacy of NAC for relieving dryness symptoms in SjD., Methods: In this placebo-controlled double-blind trial, 60 adult SjD females (with low disease activity) were randomised to receive NAC (1,200 mg/day orally) or placebo. At baseline (D0), 30 days (D30) and 90 days (D90), all participants underwent the following evaluations: EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Ocular Surface Disease Index (OSDI), Xerostomia Inventory (XI), Leicester Cough Questionnaire (LCQ), unstimulated/stimulated salivary flow, Schirmer's test, and plasma levels of thiobarbituric acid reactive substances (TBARS), glutathione and NAC., Results: At inclusion, both groups were balanced for age, ethnicity, disease duration, ESSPRI, OSDI, XI, Schirmer's test, salivary flow, ESSDAI and topical/systemic treatments (p>0.05). No significant differences were observed between NAC and placebo groups on D30 and D90 regarding ESSPRI, XI, OSDI, LCQ, Schirmer's test, stimulated salivary flow, ESSDAI and topical/systemic treatments (p>0.05). Unstimulated salivary flow was significantly higher in the placebo group on D90 (p=0.018). NAC blood concentrations were significantly higher in the NAC group on D30 (p=0.018) and D90 (p<0.001), however, no differences were found in TBARS and glutathione. Further analysis showed decrease≥1 in ESSPRI in the NAC compared with placebo group on D30 (p=0.045), a result not found on D90 (p=0.696)., Conclusions: NAC is recommended as a rescue therapy for SjD. However, our well-designed study provides novel evidence demonstrating its inefficacy for improving dryness symptoms or reducing oxidative stress., Clinicaltrials: gov-NCT04793646.

Rhabdomyolysis is characterized by muscle damage and leads to acute kidney injury (AKI). Clinical and experimental studies suggest that glycogen synthase kinase 3β (GSK3β) 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 GSK3β, 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 GSK3β 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 GSK3β and possibly associated with a decrease in muscle injury., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shimizu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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 β 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bernardo, Canale, Nascimento, Shimizu, Seguro, de Bragança and Volpini.)