Hepatocyte Growth Factor Reduces Free Cholesterol-Mediated Lipotoxicity in Primary Hepatocytes by Countering Oxidative Stress.

Cholesterol overload in the liver has shown toxic effects by inducing the aggravation of nonalcoholic fatty liver disease to steatohepatitis and sensitizing to damage. Although the mechanism of damage is complex, it has been demonstrated that oxidative stress plays a prominent role in the process. In addition, we have proved that hepatocyte growth factor induces an antioxidant response in hepatic cells; in the present work we aimed to figure out the protective effect of this growth factor in hepatocytes overloaded with free cholesterol. Hepatocytes from mice fed with a high-cholesterol diet were treated or not with HGF, reactive oxygen species present in cholesterol overloaded hepatocytes significantly decreased, and this effect was particularly associated with the increase in glutathione and related enzymes, such as γ-gamma glutamyl cysteine synthetase, GSH peroxidase, and GSH-S-transferase. Our data clearly indicate that HGF displays an antioxidant response by inducing the glutathione-related protection system.

Dicholesteroyl diselenide: cytotoxicity, genotoxicity and mutagenicity in the yeast Saccharomyces cerevisiae and in Chinese hamster lung fibroblasts.

The organoselenium compound, dicholesteroyl diselenide (DCDS) is a structural analogue of diphenyl diselenide (DPDS) and may be considered as a promising antioxidant drug in vivo. Nevertheless, little is known about the toxicological properties of DCDS. In the present study we evaluated the cytotoxic, genotoxic and mutagenic properties of DCDS in Chinese hamster lung fibroblasts (V79) and in strains of the yeast Saccharomyces cerevisiae, proficient and deficient in several DNA-repair pathways. The results with V79 cells show that DCDS induced cytotoxicity, GSH depletion and elevation of lipid peroxidation at lower concentrations than did DPDS. DCDS also generated single- and double-strand DNA breaks in V79 cells, both in the presence and in the absence of metabolic activation, as revealed by alkaline and neutral comet assays. Moreover, the induction of oxidative DNA base-damage was demonstrated by means of a modified comet assay with formamidopyrimidine-DNA glycosylase and endonuclease III. Treatment with DCDS also induced micronucleus formation in V79 cells as well as point and frame-shift mutations in a haploid wild-type strain of S. cerevisiae. Yeast mutants defective in base excision-repair proteins were the most sensitive to DCDS. Pre-incubation with N-acetylcysteine reduced DCDS's oxidative, genotoxic and mutagenic effects in yeast and in V79 cells. Our findings indicate that the presence of cholesteroyl substituents in DCDS results in elevation of its cytotoxic and genotoxic potential compared with that of DPDS in yeast and in V79 cells. However, due to dose-dependent contrasting behaviour of organoselenium compounds and differences in their toxicity in in vitro and in vivo systems, further studies are needed in order to establish the non-toxic concentration range for treatment in mammals.

Influência da ração com extratos naturais na qualidade e estabilidade oxidativa da carne de frangos / Influence of fed with natural extracts in the quality and stability of chicken meat

As exigências pela qualidade da carne estão cada vez maiores tanto no mercado internacional como no nacional, pois o consumidor está cada vez mais ciente dos atributos da qualidade da carne. Essas exigências provocaram mudanças e envolvem toda a cadeia produtiva, desde a formulação das dietas dos animais, criação até a transformação em carne. A oxidação dos lipídios da carne ou de um produto cárneo é o principal processo pelo qual ocorre perda de qualidade, depois da deterioração microbiana, e pode ser acelerada por fatores internos ou externos ao organismo animal diminuindo a proteção natural dos tecidos. A vitamina E (α-tocoferol) se distribui nas membranas celulares, protegendo os tecidos da oxidação iniciada pelos radicais livres, e pode ter sua concentração incrementada pela suplementação na dieta das aves. Estudos recentes apontam que compostos fenólicos presentes em óleos essenciais de especiarias como orégano, alecrim e sálvia são efetivos em preservar a estabilidade oxidativa da carne, mesmo quando fornecidos por meio da alimentação e são desejáveis por serem naturais. Este estudo teve como objetivo principal estudar os efeitos da adição de extratos de antioxidantes naturais na dieta de frangos de corte e também da suplementação com vitamina E, na qualidade e estabilidade oxidativa de sobrecoxas desses animais e de almôndegas preparadas a partir destes cortes...

Studies on the antioxidant effect and interaction of diphenyl diselenide and dicholesteroyl diselenide with hepatic delta-aminolevulinic acid dehydratase and isoforms of lactate dehydrogenase.

Studies on the interaction of dicholesteroyl diselenide (DCDS) and diphenyl diselenide (DPDS) with hepatic delta-aminolevulinic acid dehydratase (ALA-D) and different isoforms of lactate dehydrogenase (LDH) from different tissues were investigated. In addition, their antioxidant effects were tested in vitro by measuring the ability of the compounds to inhibit the formation of hepatic thiobarbituric acid reactive species (TBARS) induced by both iron (II) and sodium nitroprusside (SNP). The results show that while DPDS markedly inhibited the formation of TBARS induced by both iron (II) and SNP, DCDS did not. Also, the activities of hepatic delta-aminolevulinic acid dehydratase (ALA-D) and different isoforms of lactate dehydrogenase (LDH) were significantly inhibited by both DPDS and DCDS. Moreover, we further observed that the in vitro inhibition of different isoforms of lactate dehydrogenase by DCDS and DPDS likely involves the modification of the groups at the NAD+ binding site of the enzyme. Since organoselenides interacts with thiol groups on proteins, we conclude that the inhibition of different isoforms of lactate dehydrogenase by DPDS and DCDS possibly involves the modification of the thiol groups at the NAD+ binding site of the enzyme.