Uric acid and kidney damage in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs; lupus nephritis (LN) is one of the most severe complications of SLE. In the kidneys, an intense inflammatory reaction affects the glomeruli and tubular interstitium. Uric acid has been considered a key molecule in the pathogenesis of some conditions such as metabolic syndrome, hypertension, and kidney disease as it is produced by injured cells and promotes immune-inflammatory responses. In this regard, high serum uric acid concentrations may be involved in the activation of some inflammatory pathways, associated with kidney damage in SLE. Therefore, the purpose of this article was to review the main physiological mechanisms and clinical data on the association between serum uric acid and kidney damage in SLE. Scientific evidence indicates that hyperuricemia has the potential to be an adjuvant in the development and progression of kidney manifestations in SLE. Uric acid may promote the activation of inflammatory pathways and the formation and deposition of autoantibodies in kidneys, leading to a reduction of glomerular filtration rate. Other potential mechanisms of this association include the presence of polymorphisms in the urate transporters, metabolic syndrome, use of some medications, and other situations associated with a reduced renal excretion of uric acid.

NLRP3 Inflammasome Modulation by Melatonin Supplementation in Chronic Pristane-Induced Lupus Nephritis.

Lupus nephritis (LN) is a kidney inflammatory disease caused by systemic lupus erythematosus (SLE). NLRP3 inflammasome activation is implicated in LN pathogenesis, suggesting its potential targets for LN treatment. Melatonin, an endogenous indoleamine, is considered an important multitasking molecule that has been reported to have anti-inflammatory effects by inhibiting nuclear factor-kappa B (NF-κB)-mediated inflammatory responses in vivo. This molecule has also protective effects against the activation of the inflammasomes and, in particular, the NLRP3 inflammasome. Thus, this work evaluated the effect of melatonin on morphological alteration and NLRP3 inflammasome activation in LN pristane mouse models. To evaluate the melatonin effects in these mice, we studied the renal cytoarchitecture by means of morphological analyses and immunohistochemical expression of specific markers related to oxidative stress, inflammation and inflammasome activation. Our results showed that melatonin attenuates pristane-induced LN through restoring of morphology and attenuation of oxidative stress and inflammation through a pathway that inhibited activation of NLRP3 inflammasome signaling. Our data clearly demonstrate that melatonin has protective activity on lupus nephritis in these mice that is highly associated with its effect on enhancing the Nrf2 antioxidant signaling pathway and decreasing renal NLRP3 inflammasome activation.

Protective effects of quercetin treatment in a pristane-induced mouse model of lupus nephritis.

INTRODUCTION: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus. As murine models of LN are valuable tools to better understand its pathophysiology and to search for new effective treatments, we investigated the effects of the bioflavonoid quercetin on pristane-induced LN mice through histomorphological analyses. METHODS: Immunofluorescence and biochemical assays were used to evaluate the expression of markers of inflammation (interleukin-6, IL-6; tumour necrosis factor-α, TNF-α), oxidative stress (catalase, CAT; superoxide dismutase 1, SOD1; thiobarbituric acid reactive substances, TBARS), apoptosis (Bax), and fibrosis (transforming growth factor-ß1, TGF-ß1). Glomerular and tubular ultrastructure was analysed, and tissue messenger RNA of podocin, podoplanin and α3ß1-integrin were quantified using the real-time polymerase chain reaction. RESULTS: Pristane-induced LN mice showed severe kidney injury, characterized by increased proteinuria, glomerular mesangial expansion and inflammation, high expression of the pro-fibrotic, apoptotic and prooxidant markers and reduction of antioxidants. In the kidney ultrastructure, foot process (FP) effacement, apoptotic mesangial cells and abnormal mitochondria with disrupted cristae were observed, along with suppressed tissue mRNA of podocin, podoplanin and α3ß1-integrin. Treatment with quercetin in the pristane-induced LN mice model was nephroprotective, decreasing proteinuria levels and significantly lowering tissue expression of IL-6, TNF-α, TGF-ß1, Bax and TBARS. Simultaneously, quercetin significantly increased CAT and SOD1 expressions in these mice. In addition, it was observed improvement of the kidney ultrastructure, and tissue mRNA of podocin, but not podoplanin and α3ß1-integrin, was restored to the levels found in the control mice. CONCLUSION: In conclusion, these findings provide experimental evidence of the renoprotective effects of quercetin in the pristane-induced LN mice model. We suggest that quercetin effectively ameliorates the kidney damage caused by pristane, a bioflavonoid to be further evaluated as a new therapeutic strategy in this disease.

Oral supplementation of melatonin protects against lupus nephritis renal injury in a pristane-induced lupus mouse model.

AIMS: Since lupus nephritis (LN) etiopathogenesis is not fully understood, herein we investigated the morphological basis of LN in mice induced with pristane. MAIN METHODS: To evaluate the melatonin effects in these animals, we studied the renal cytoarchitecture by means of morphological analyses, immunofluorescence expression of specific markers related to fibrosis, oxidative stress, inflammation and apoptosis. KEY FINDINGS: We observed that pristane-LN mice have serious alterations in the kidney cytoarchitecture, i.e. tubular degeneration, glomerular hypercellularity, matrix mesangial expansion and interstitial inflammation. The pristane-induced LN mice treated with melatonin exhibited a well preserved cytoarchitecture. SIGNIFICANCE: Our results document that LN etiopathogenesis is related to both tubular damage and glomerular lesions. We suggest that it is essential to take in consideration both these lesions for LN diagnosis and classification. Clearly, we show that the use of melatonin may be a possible therapeutic strategy for improvement the renal injury in this disorder.