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

Abstract

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-β1, TGF-β1). Glomerular and tubular ultrastructure was analysed, and tissue messenger RNA of podocin, podoplanin and α3β1-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 α3β1-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-β1, 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 α3β1-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.

Keywords:

• Lupus nephritis
• pristane
• quercetin
• inflammation
• oxidative stress
• podocyte

Acknowledgements

We thank Luciano Pinto Guimarães for expert statistical assistance. The authors also thank Lorena Giugno for her precious technical support.

Ethics approval and consent to participate

The present study was approved by the Animal Ethics Committee of Hospital de Clínicas de Porto Alegre (HCPA, Porto Alegre, RS, Brazil) and was conducted in accordance with National Institutes of Health guidelines.

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

This study was supported by Fundo de Incentivo à Pesquisa of Hospital de Clínicas de Porto Alegre (FIPE/HCPA) and by the Federal University of Rio Grande do Sul (UFRGS), Brazil. We acknowledge the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil, for a scholarship offered to Mariane dos Santos, and for a grant provided by the CAPES-PSDE (Programa de Doutorado Sanduíche no Exterior, number 88881.134006/2016-01).