group mice drank tap water which contains 0.28 mg/250 ml boric acid. After a 5 day period, gene expression levels for UCP1, UCP2, and UCP3 in the white adipose tissue (WAT), brown adi-pose tissue (BAT) and skeletal muscle tissue (SMT) and total body weight changes were analyzed.
Results: Real time PCR analysis revealed no significant change in UCP3 expressions but UCP2 in WAT (p: 0.0317), BAT (p: 0.014), and SMT (p: 0.0159) and UCP1 in BAT (p: 0.026) were overexpressed in the boric acid group. In addition, mice in the boric acid group lost body weight (mean 28.1%) while mice in the control group experienced no weight loss but, a slight weight gain (mean 0.09%, p< 0.001).
Conclusion: Oral boric acid intake causes overexpression of thermogenic proteins in the adipose and skeletal muscle tissues. Increasing thermogenesis through UCP protein pathway results in the accelerated lipolysis and body weight loss.
Reference
1. E. Aysan, F. Sahin, D. Telci, M.E. Yalvac, S.H. Emre, C. Karaca, M. Muslumanoglu ‘Body weight reducing effect of oral boric acid intake’ Int J Med Sci., 653–8 pp, 2011.
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Sodium tungstate decreases the progression
of renal damage through inhibition of fibrosis
in diabetic rat kidney
P. Silva, K. Jaramillo, D. Carpio, M. Perez and A. Yanez Universidad Austral de Chile, Valdivia, Chile
Diabetes mellitus is a condition in which the metabolism of car-bohydrates, lipids and proteins are inadequately regulated by insulin. One of their complications is diabetic nephropathy, where pathological accumulation of extracellular matrix proteins and renal fibrosis are the fundamental mechanisms by which this disease progresses to end-stage renal failure. In this study, we evaluate the progression of renal damage in long term streptozo-tocin-induced diabetic rats through anatomopathological and biochemical analysis and we evaluated the effect of sodium tung-state (NaW) on the diabetic nephropathy. The anatomopatholog-ical analysis showed glomerullar damage since 4 months of diabetes and increases constantly to 8 months. At the final stage we found damage in glomerulli by observing increased glomerul-lar sclerosis (16%). Moreover, tubuglomerul-lar damage is the first to appear beginning in the second month of induction of diabetes. Surprisingly, sodium tungstate reduced the progression of nephropathy on early and long-treated diabetic rats. In addition, we evaluated the expression of several markers of fibrosis in the progression of this pathology. We observe that the increase in the protein levels of type IV-collagen and a-SMA produced by renal damage were reverted by treatment with sodium tungstate. Our results indicate that damage progression in diabetic nephrop-athy is guided by a process involving fibrosis and sodium tung-state treatment is able to reverse this process and slow down the progression of kidney damage (FONDECYT 1131033).
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Sodium tungstate attenuates fibrosis through
suppression of transforming growth factor-
b1/
Smad3 in diabetic nephropathy
K. Jaramillo, D. Mansilla, A. Cumian, M. Perez, D. Carpio, R. Burgos and A. Yanez
Universidad Austral de Chile, Valdivia, Chile
Diabetes mellitus induces significant complications in human patients, among these diabetic nephropathy (DN). Sodium tung-state (Na2WO4) has been described as a potent
normoglicemian-te by exerting an insulin mimetic action. In the present study, we sought to investigate the effect of Na2WO4 and its mechanism of action on renal glomerular and tubulointerstitial fibrosis in strep-tozotocin-induced diabetic rats, an animal model of type I diabe-tes mellitus. After 4 months of diabediabe-tes, kidney damage was characterized by biochemical and anatomic pathology. The ultra-structural alterations were evaluated by electron microscopy. Pro-tein analyses were performed by Western blot and immunostaining. The diabetic condition of rats was associated with an increase in collagen anda-smooth muscle actin accumu-lation in the kidney, which was significantly reduced by Na2WO4. The transforming growth factor (TGF)-b1 and phos-pho-Smad3 proteins were significantly higher in STZ animals compared with control animals. This increase in TGF-b1 expres-sion and Smad3 phosphorylation was greatly attenuated by Na2WO4 in the diabetic kidneys. Taken together, Na2WO4 sup-pressed TGF-b1/Smad3 signaling pathways and reduced glomer-ular and tubulointerstitial fibrosis in diabetic STZ animals. We observed decrease fibrosis and inhibition of the kidney damage detected by large decrease of the accumulation of collagen sug-gesting that this drug could be effective treatment to prevent renal fibrosis in advanced stages of diabetic nephropathy. (CON-ICYT 24110230).
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Post-translational modulation of hydrogen
peroxidation enzymes by streptozotocin
induced diabetes and antioxidants
G. Sadi, D. Bozan and H. B. Yildiz
Karamanoglu Mehmetbey University, Karaman, Turkey
Present study investigated the changes in gene and protein expres-sions as well as catalytic activities of catalase and glutathione per-oxidase by diabetes and antioxidants. Total protein, catalase and glutathione peroxidase phosphorylation levels were also determined. According to results; phosphoprotein profiles of diabetic and anti-oxidant treated rats were modified and total protein phosphoryla-tion was increased by diabetes and vitamin C. As parallel with mRNA, total catalase protein amount and activity were also decreased in diabetes and both antioxidants elevated this reduction towards the control levels. Unlike total catalase, phospho catalase levels were further suppressed by diabetes and antioxidant treat-ments. Moreover, diabetes and antioxidants did not change the un-phospho and un-phospho glutathione peroxidase protein levels. Findings revealed that suppression of catalase activity in diabetes were at the level of gene expression and its activity was further modulated by a post-translational mechanism mostly via phosphor-ylation with diabetes and antioxidants mainly with vitamin C.
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Metabolic aspects of toxication and
detoxication of the anticancer agent ellipticine
determining its pharmacological efficiencies
M. Stiborova
Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic
The anti-tumor therapeutic ellipticine is a prodrug, whose phar-macological efficiency is dictated by its cytochrome P450 (CYP) and/or peroxidase-mediated activation in target tissues. The CYP1A1-mediated ellipticine metabolites 9-hydroxy- and 7-hy-droxyellipticine and the product of ellipticine oxidation by perox-idases, the ellipticine dimer, are the ellipticine detoxication metabolites. In contrast, two carbenium ions, ellipticine-13-ylium and ellipticine-12-ylium, derived from two activation ellipticine
300 FEBS Journal 280 (Suppl. 1) (2013) 3–617
ª 2013 The Authors. FEBS Journal ª 2013 FEBS
