Acinar adipose tissue infiltration in salivary gland biopsy is associated with kynurenines-Interferon-γ pathway inflammation biomarkers.

OBJECTIVES: Assess if kynurenines metabolites are biomarkers of damage at labial salivary gland biopsy (LSGB). METHODS: This is a cross-sectional study including 99 patients with primary Sjögren's syndrome (AECG 2002 or ACR/EULAR 2017). Kynurenines were measured in plasma using liquid chromatography-tandem mass spectrometry. RESULTS: 95.9% were females, 51±12 years. Most had focal lymphocytic sialadenitis with focus score ≥1 (73.7%, n=73/99). The majority had mild to severe acinar atrophy (70.4%, n=57/81) and adipose infiltration (51.2%, n=39/80). Individuals with adipose infiltration were older (53.49±12.33 vs. 47.51±11.29 years, p=0.016), showed higher frequency of glandular dysfunction and higher kynurenines levels. Schirmer's test ≤ 5 mm/5min was found in 69.2% of individuals with adipose infiltration compared to 41% without (p=0.012) and unstimulated whole salivary flow (UWSF) was found in 87.2% compared to 70% without adipose infiltration (p=0.063). Additionally, individuals with adipose infiltration showed higher kynurenines metabolites compared with those without: quinolinic acid (503.35±193.30 vs. 427.35±285.76 nmol/L, p=0.029), kynurenine (1.99±0.6, 54 vs. 1.61±0.46 µmol/L, p=0.006), kynurenine/tryptophan ratio (KTR) (0.030±0.09 vs. 0.025±0.01, p=0.031) and anthranilic acid (03±4.96 vs. 16.46±5.24 nmol/L, p=0.022). CONCLUSIONS: Kynurenines are biomarkers of greater adipose infiltration in LSGB and glandular dysfunction suggesting that activation of interferon-γ pathway is involved in the salivary and lacrimal glands damage.

Renoprotective, anti-oxidative and anti-apoptotic effects of oral low-dose quercetin in the C57BL/6J model of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease in diabetic patients. Increasing evidence from studies in the rodents has suggested that this disease is associated with increased oxidative stress due to hyperglycemia. In the present study, we evaluated the renoprotective, anti-oxidative and anti-apoptotic effects of the flavonoid quercetin in C57BL/6J model of DN. METHODS: DN was induced by streptozotocin (STZ, 100 mg/kg/day, for 3 days) in adult C57BL/6J mice. Six weeks later, mice were divided into the following groups: diabetic mice treated with quercetin (DQ, 10 mg/kg/day, 4 weeks), diabetic mice treated with vehicle (DV) or non-treated non-diabetic (ND) mice. RESULTS: Quercetin treatment caused a reduction in polyuria (~45%) and glycemia (~35%), abolished the hypertriglyceridemia and had significant effects on renal function including, decreased proteinuria and high plasma levels of uric acid, urea and creatinine, which were accompanied by beneficial effects on the structural changes of the kidney including glomerulosclerosis. Flow cytometry showed a decrease in oxidative stress and apoptosis in DN mice. CONCLUSION: Taken together, these data show that quercetin effectively attenuated STZ-induced cytotoxicity in renal tissue. This study provides convincing experimental evidence and perspectives on the renoprotective effects of quercetin in diabetic mice and outlines a novel therapeutic strategy for this flavonoid in the treatment of DN.