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.

Neurobehavioral effects of L-carnitine and its ability to modulate genotoxicity and oxidative stress biomarkers in mice.

L-Carnitine, a natural vitamin-like compound supplied to the body by biosynthesis and dietary sources, has been shown to exert beneficial effects in disorders affecting cardiovascular, urinary, and nervous systems. However, the paucity of data on its effects does not guarantee the safe use of L-carnitine as a nutritional supplement, and further pre-clinical studies are required to assess toxicological aspects. The present study evaluated the effects of L-carnitine (10, 50 or, 100 mg/kg) in mice, in the open field test. Also, lipoperoxidation was assessed measuring thiobarbituric acid reactive substances (TBARS) and genotoxic/antigenotoxic activities were evaluated using the comet assay in several tissues. L-Carnitine 50 mg/kg impaired exploration, though with no effects on habituation to a novel environment. L-Carnitine increased TBARS in the brain and liver tissues, but it did not induce genotoxicity in any tissue. In ex vivo comet assay, a decrease in DNA damage in the blood and liver tissues was observed, while the opposite occurred in the brain tissue. In conclusion, L-carnitine may increase lipid peroxidation, though without inducing genotoxic effects, protect DNA against endogenous and induced oxidative damages in blood and liver; however, L-carnitine impaired exploratory behavior and increased the vulnerability of the brain tissue to oxidative stress, suggesting that the excessive consumption of L-carnitine may promote deleterious effects on the central nervous system.