Vanadyl sulphate ameliorates biomarkers of endothelial injury and coagulation and thrombosis in a rat model of hyperglycaemia.

BACKGROUND: We sought to determine whether the insulin mimicking agent, vanadyl sulphate (Van) can inhibit biomarkers of endothelial injury and coagulation and thrombosis induced by a moderate level of hyperglycaemia. MATERIAL AND METHODS: Hyperglycaemia was induced in rats by a single injection of streptozotocin (STZ, 50 mg/kg) two weeks after being fed on a high-fat diet (model group). The treatment group started Van (20 mg/kg/day) treatment one-week post STZ injection and continued on Van until being sacrificed at week 10. RESULTS: Administration of Van to the model group significantly (p < .05) ameliorated dyslipidemia and biomarkers of inflammation (TNF-α, IL-6, and hsCRP) and endothelial injury (E-selectin, P-selectin, sICAM-1, sVCAM-1, and ET-1). Van also significantly inhibited hyperglycaemia-induced blood levels of coagulation (vWF) and thrombosis (PAI-1 and fibrinogen) biomarkers. CONCLUSIONS: Vanadyl sulphate effectively suppresses hyperglycaemia-induced endothelial injury, coagulation and thrombosis, which is associated with the inhibition of inflammation and dyslipidemia.

Suppression of glomerular damage and apoptosis and biomarkers of acute kidney injury induced by acetaminophen toxicity using a combination of resveratrol and quercetin.

Acute renal failure induced by a toxic dose of acetaminophen (also known as paracetamol, or APAP) is common in both humans and experimental animal models. Glomerular ultrastructural alterations induced by APAP overdose associated with the suppression of biomarkers of kidney injury have not been investigated before. Also, we investigated whether the combined polyphenolic antioxidants and anti-inflammatory compounds, resveratrol (RES) and quercetin (QUR) can protect against APAP-induced nephrotoxicity. Rats either received a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pretreated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. APAP significantly (p < 0.05) increased blood levels of urea, creatinine, malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), which were effectively reduced by RES + QUR. In addition, APAP overdose induced the tissue expression of the apoptotic biomarker, p53, and caused profound kidney damage as demonstrated by substantial alterations to the glomerular basement membrane, podocytes, endothelial cells, widening of Bowman's space, and vacuolation of the cells lining the parietal layer, which were substantially protected by RES + QUR. Furthermore, a significant (p < 0.0001) positive correlation was observed between either glomerular basement membrane or podocyte foot processes and these parameters, urea, creatinine, MDA, and TNF-α. Thus, we conclude that APAP induces alterations to the glomerulus ultrastructure, which is protected by resveratrol plus quercetin, which also reduces blood levels of urea and creatinine, and biomarkers of oxidative stress and inflammation.