Ursodeoxycholic acid ameliorates fructose-induced metabolic syndrome in rats.

The metabolic syndrome (MS) is characterized by insulin resistance, dyslipidemia and hypertension. It is associated with increased risk of cardiovascular diseases and type-2 diabetes. Consumption of fructose is linked to increased prevalence of MS. Ursodeoxycholic acid (UDCA) is a steroid bile acid with antioxidant, anti-inflammatory activities and has been shown to improve insulin resistance. The current study aims to investigate the effect of UDCA (150 mg/kg) on MS induced in rats by fructose administration (10%) in drinking water for 12 weeks. The effects of UDCA were compared to fenofibrate (100 mg/kg), an agonist of PPAR-α receptors. Treatment with UDCA or fenofibrate started from the 6th week after fructose administration once daily. Fructose administration resulted in significant increase in body weight, elevations of blood glucose, serum insulin, cholesterol, triglycerides, advanced glycation end products (AGEs), uric acid levels, insulin resistance index and blood pressure compared to control rats. Moreover, fructose increased oxidative stress in aortic tissues indicated by significant increases of malondialdehyde (MDA), expression of iNOS and reduction of reduced glutathione (GSH) content. These disturbances were associated with decreased eNOS expression, increased infiltration of leukocytes and loss of aortic vascular elasticity. Treatment with UDCA successfully ameliorated the deleterious effects of fructose. The protective effect of UDCA could be attributed to its ability to decrease uric acid level, improve insulin resistance and diminish oxidative stress in vascular tissues. These results might support possible clinical application of UDCA in MS patients especially those present with liver diseases, taking into account its tolerability and safety. However, further investigations on human subjects are needed before the clinical application of UDCA for this indication

Spirulina platensis Lacks Antitumor Effect against Solid Ehrlich Carcinoma in Female Mice

Spirulina is a blue-green alga used as a dietary supplement. It has been shown to possess anti-inflammatory, antioxidant, and hepatoprotective properties. This study was designed to evaluate the antitumor effect of spirulina (200 and 800 mg/kg) against a murine model of solid Ehrlich carcinoma compared to a standard chemotherapeutic drug, 5-fluorouracil (20 mg/kg). Untreated mice developed a palpable solid tumor after 13 days. Unlike fluorouracil, spirulina at the investigated two dose levels failed to exert any protective effect. In addition, spirulina did not potentiate the antitumor effect of fluorouracil when they were administered concurrently. Interestingly, their combined administration resulted in a dose-dependent increase in mortality. The present study demonstrates that spirulina lacks antitumor effect against this model of solid Ehrlich carcinoma and increased mortality when combined with fluorouracil. However, the implicated mechanism is still elusive

Histological examination of aortic sections stained with H&E (×400) on the right panel and Weigert's elastic stain (×400) on the left panel.

<p>Representative aortic sections were obtained from control rats (a); FDR (b); FDR administered UDCA 150 mg/kg (c) and FDR administered fenofibrate 100 mg/kg (d). White arrowheads point to the relatively straight elastic laminae of aorta from FDR. FDR, fructose-drinking rats; UDCA, ursodeoxycholic acid.</p

Effect of ursodeoxycholic acid (150 mg/kg, p.o.) and fenofibrate (100 mg/kg, p.o.) on gene expression of iNOS (a); eNOS (b) and XO (c) of aortic sections isolated from fructose-drinking rats.

<p>(n = 5–8). ^*P<0.05 vs. control, ^**P<0.05 vs. FDR. FDR, fructose-drinking rats; UDCA, fructose-drinking rats treated with ursodeoxycholic acid; FENO, fructose-drinking rats treated with fenofibrate. iNOS, inducible nitric oxide synthase; eNOS, endothelial nitric oxide synthase; XO, xanthine oxidase; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.</p

Effect of ursodeoxycholic acid (150 mg/kg, p.o.) and fenofibrate (100 mg/kg, p.o.) on body weight, serum parameters and blood pressure in rats administered fructose.

<p>Values are expressed as mean ± SEM (n = 5–8). <b>^a</b>Percentage change in body weight from basal value before starting the experiment. ^*P<0.05 vs. control, ^#P<0.05 vs. FDR. FDR, fructose-drinking rats; UDCA, fructose-drinking rats treated with ursodeoxycholic acid (150 mg/kg, p.o.); FENO, fructose-drinking rats treated with fenofibrate (100 mg/kg, p.o.). FBG, fasting blood glucose; HOMA-IR, homeostasis model assessment index for insulin resistance; T. CH, total cholesterol; TG, triglycerides; AGEs, advanced glycation end products; prot., protein; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure.</p><p>Effect of ursodeoxycholic acid (150 mg/kg, p.o.) and fenofibrate (100 mg/kg, p.o.) on body weight, serum parameters and blood pressure in rats administered fructose.</p