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.

The effect of n-3/n-6 polyunsaturated fatty acids on acute reflux esophagitis in rats.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) play various roles in inflammation. However, the effect of PUFAs in the development of reflux esophagitis (RE) is unclear. This study is to investigate the potential effect of n-3/n-6 PUFAs on acute RE in rats along with the underlying protective mechanisms. METHODS: Forty Sprague Dawley rats were randomly divided into four groups (n = 10 in each group). RE model was established by pyloric clip and section ligation. Fish oil- and soybean oil-based fatty emulsion (n-3 and n-6 groups), or normal saline (control and sham operation groups) was injected intraperitoneally 2 h prior to surgery and 24 h postoperatively (2 mL/kg, respectively). The expressions of interleukin (IL)-1ß, IL-8, IL-6 and myeloid differentiation primary response gene 88 (MyD88) in esophageal tissues were evaluated by Western blot and immunohistochemistry after 72 h. The malondialdehyde (MDA) and superoxide dismutase (SOD) expression in the esophageal tissues were determined to assess the oxidative stress. RESULTS: The mildest macroscopic/microscopic esophagitis was found in the n-3 group (P < 0.05). The expression of IL-1ß, IL-8, IL-6 and MyD88 were increased in all RE groups, while the lowest and highest expression were found in n-3 and n-6 group, respectively (P < 0.05). The MDA levels were increased in all groups (P < 0.05), in an ascending trend from n-3, n-6 groups to control group. The lowest and highest SOD levels were found in the control and n-3 group, respectively (P < 0.05). CONCLUSION: n-3 PUFAs may reduce acute RE in rats, which may be due to inhibition of the MyD88-NF-kB pathway and limit oxidative damage.