Hyperlipidemia-induced lipotoxicity and immune activation in rats are prevented by curcumin and rutin.

We assessed the effects of curcumin, rutin, and the association of rutin and curcumin in organs of hyperlipidemic rats. Rutin and curcumin have notable antioxidant and anti-inflammatory actions, so we hypothesized that their association would enhance their beneficial effects. Hyperlipidemia results in lipotoxicity and affects several organs. Lipotoxicity is not only an outcome of lipid accumulation in non-adipose tissues but also a result of the hyperlipidemia-associated inflammation and oxidative stress. Wistar rats were treated with rutin and curcumin for 30 days before the induction of acute hyperlipidemia by Poloxamer-407. After 36 h, the animals were euthanized for collection of blood and organs. Untreated hyperlipidemic rats showed higher uric acid and albumin levels in the serum and increased spleen size and ADA activity. Rutin, curcumin and the association reduced the spleen size by 20% and ADA activity by 23, 28, and 27%, respectively. Rats pretreated with rutin showed reduced lipid damage in the liver (40%) and the kidney (44%), and the protein damage was also reduced in the liver (75%). The lipid damage was decreased by 40% in the liver, and 56% in the kidney of rats pretreated with curcumin. The association reduced lipid damage by 50% and 36%, and protein damage by 77% and 64% in the liver and kidney, respectively. Rutin better prevented the decrease in the antioxidant defenses, increasing SOD by 34%, CAT by 246% and GST by 84% in the liver, as well as SOD by 119% and GST by 190% in the kidney. Also, analyses of blood and spleen parameters of untreated and pretreated non-hyperlipidemic rats showed no signs of immunotoxicity. Despite showing protective effects, the association did not perform better than the isolated compounds. Here, we showed that rutin and/or curcumin reestablished the immune homeostasis and redox balance disrupted by hyperlipidemia in peripheral organs of rats.

Effects of diphenyl diselenide diet on a model of mercury poisoning.

This work investigated the preventive effect of diphenyl diselenide [(PhSe)2] against the toxic effects of mercury in silver catfish (Rhamdia quelen). The animals were treated during 30 consecutive days with a (PhSe)2 supplemented feed (3.0 mg kg-1) or commercial feed. During the last 5 days the animals received a daily intraperitoneal dose of HgCl2 (1.7 mg kg-1) or Saline (0.9%). Twenty-four hours after the last HgCl2 injection, the animals were euthanized by spinal cord section to biological material obtainment. Hepatic (AST and ALT) and renal (ammonia and creatinine) toxicity biomarkers, δ-ALA-D activity, TBARS, total and non-protein thiols levels and hepatic, renal and blood mercury (Hg) and zinc (Zn) content were evaluated. Considering renal parameters, HgCl2 exposition increased serum creatinine levels and decreased δ-ALA-D activity, total and non-protein thiols and TBARS levels. HgCl2 exposure also decreased blood δ-ALA-D activity. With exception of blood δ-ALA-D activity and total thiols levels, (PhSe)2 supplementation partially prevented mercury induced alterations. Animals exposed to HgCl2 presented an increase in liver and kidney Hg content and a decrease in liver and blood Zn content. The alteration in blood Zn content was partially prevented with (PhSe)2 supplementation. With the exception of mercury and zinc content, no effects of HgCl2 exposure on hepatic tissue were observed. These results show that (PhSe)2 supplementation can represent a promising alternative to prevent the toxic effects presented by Hg exposure.

Effect of diphenyl diselenide diet supplementation on oxidative stress biomarkers in two species of freshwater fish exposed to the insecticide fipronil.

The ability of diphenyl diselenide [(PhSe)2] to attenuate oxidative damage was evaluated in the liver, gills, brain, and muscle of carp (Cyprinus carpio) and silver catfish (Rhamdia quelen) experimentally exposed to fipronil (FPN). Initially, the fish were fed a diet without (PhSe)2 or a diet containing 3.0 mg/kg of (PhSe)2 for 60 days. After the 60-day period, the fish were exposed to 0.65 µg/L of FPN for 192 h. The results showed that carp exposed to FPN and not fed with (PhSe)2 exhibited acetylcholinesterase (AChE) inhibition in brain and muscle, and increased thiobarbituric acid-reactive substance (TBARS) in liver, gills, and brain. Furthermore, FPN decreased nonprotein thiols (NPSH) and δ-aminolevulinate dehydratase (δ-ALA-D) in carp liver and gills, and increased plasma glucose and protein levels. In silver catfish, FPN inhibited AChE and increased TBARS levels in muscle. In addition, glutathione S-transferase (GST) decreased in liver and muscle, and plasma glucose was increased. (PhSe)2 reversed some of these effects. It prevented the increase in TBARS levels in liver, gills, and brain in carp and in silver catfish muscle, and reversed the increase in plasma glucose levels in both species. Additionally, (PhSe)2 increased the NPSH levels in carp and silver catfish that had decreased in response to FPN exposure. However, (PhSe)2 was not effective in reversing the AChE inhibition in brain and muscle or the δ-ALA-D decrease in carp liver. Thus, (PhSe)2 protects tissues of both species of fish, mainly by preventing or counteracting the effects of FPN, on TBARS levels, antioxidants, and present anti-hyperglycemic property.

Effects of diphenyl diselenide on growth, oxidative damage, and antioxidant response in silver catfish.

The aim of this study was to evaluate the effects of dietary diphenyl diselenide [(PhSe)2] at different concentrations (1.5, 3.0, and 5.0 mg/kg) on growth, oxidative damage and antioxidant parameters in silver catfish after 30 and 60 days. Fish fed with 5.0 mg/kg of (PhSe)2 experienced a significant decrease in weight, length, and condition factor after 30 days and these parameters increased after 60 days. Thiobarbituric acid reactive substances (TBARS) and protein carbonyl (PC) decreased in the liver of silver catfish supplemented with (PhSe)2 after 30 days at all concentrations, while after 60 days these parameters decreased in liver, gills, brain, and muscle. Supplementation with (PhSe)2 induced a decrease in catalase (CAT) activity from liver only after 60 days of feeding. Superoxide dismutase (SOD) decreased at 5.0 mg/kg after 30 and 60 days and glutathione peroxidase (GPx) was enhanced at 1.5 and 3.0 mg/kg after 30 and 60 days. Silver catfish supplemented for 30 days showed a significant increase in liver glutathione S-transferase (GST) at 3.0 mg/kg, while after 60 days GST activity increased in liver at 1.5, 3.0, and 5.0 mg/kg and in gills at 3.0 and 5.0 mg/kg of (PhSe)2. After 30 days, non-protein thiols (NPSH) did not change, while after 60 days NPSH increased in liver, gills, brain, and muscle. In addition, ascorbic acid (AA) levels after 30 days increased in liver at three concentrations and in gills and muscle at 1.5 mg/kg, while after 60 days, AA increased at all concentrations in all and tissues tested. Thus, diet supplemented with (PhSe)2 for 60 days could be more effective for silver catfish. Although the concentration of 5.0 mg/kg showed decreased growth parameters, concentrations of 1.5 and 3.0 mg/kg, in general, decreased oxidative damage and increased antioxidant defenses.

Diet with diphenyl diselenide mitigates quinclorac toxicity in silver catfish (Rhamdia quelen).

In this study, the protective effects of diphenyl diselenide [(PhSe)2] on quinclorac- induced toxicity were investigated in silver catfish (Rhamdia quelen). The fish were fed for 60 days with a diet in the absence or in the presence of 3.0 mg/Kg (PhSe)2. Animals were further exposed to 1 mg/L quinclorac for 8 days. At the end of experimental period, fish were euthanized and biopsies from liver and gills, as well as blood samples, were collected. The cortisol and metabolic parameters were determined in plasma, and those enzyme activities related to osmoregulation were assayed in the gills. In liver, some important enzyme activities of the intermediary metabolism and oxidative stress-related parameters, such as thiobarbituric acid-reactive substance (TBARS), protein carbonyl, catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), nonprotein thiols (NPSH) and ascorbic acid contents were also evaluated. Compared to the control group, quinclorac exposure significantly decreased hepatosomatic index and increased cortisol and lactate values in plasma. Moreover, the activities of fructose biphosphatase (FBPase), glucose-6-phosphate dehydrogenase (G6Pase), glycogen phosphorilase (GPase) and aspartate aminotransferase (AST) were significantly increased in liver. Quinclorac also induced lipid peroxidation while the activity of SOD, NPSH and ascorbic acid levels decreased in the liver. However, dietary (PhSe)2 reduced the herbicide-induced effects on the studied parameters. In conclusion, (PhSe)2 has beneficial properties based on its ability to attenuate toxicity induced by quinclorac by regulating energy metabolism and oxidative stress-related parameters.

Evaluation of the effects induced by dietary diphenyl diselenide on common carp Cyprinus carpio.

Several diets employed in aquaculture are enriched with selenium (Se), as it is a fundamental element to aquatic vertebrates. Diphenyl diselenide [(PhSe)2], which is a synthetic organoselenium compound, has been considered a potential antioxidant agent in different experimental models. Thus, the aim of this study was to evaluate the effects of dietary diphenyl diselenide at concentrations of 1.5, 3.0, and 5.0 mg/kg for 60 days and to determine its optimal supplemental level for carp, Cyprinus carpio. Neither growth retardation nor hepatoxicity was induced by the inclusion of diphenyl diselenide at concentrations ranging from 1.5 to 5.0 mg/kg. In addition, the inclusion of 3.0 mg/kg of diphenyl diselenide stimulated the weight and length of the carp. The supplementation with 1.5 and 3.0 mg/kg of diphenyl diselenide did not produce oxidative damage in the tissues, verified by peroxidation lipid and protein carbonyl assays. However, at 5.0 mg/kg, it caused an increase of the lipid peroxidation in the liver, brain, and muscle, and inhibited the cerebral acetylcholinesterase activity. An increase of the hepatic superoxide dismutase activity and non-protein thiols content in all tissues and ascorbic acid in the liver, gills, and brain was verified in carp fed with the diet containing 3.0 mg/kg of diphenyl diselenide. This diet had advantageous effects for the fish used in experiments. Therefore, this compound could be considered a beneficial dietary supplement for carp nutrition.

Comparative study on effects of dietary with diphenyl diselenide on oxidative stress in carp (Cyprinus carpio) and silver catfish (Rhamdia sp.) exposed to herbicide clomazone.

The study investigated the capacity of diphenyl diselenide [(PhSe)2] (3.0mg/kg), on reduce the oxidative damage in liver, gills and muscle of carp and silver catfish exposed to clomazone (192h). Silver catfish exposed to clomazone showed increased thiobarbituric acid-reactive substance (TBARS) in liver and muscle and protein carbonyl in liver and gills. Furthermore, clomazone in silver catfish decrease non-protein thiols (NPSH) in liver and gills and glutathione peroxidase and ascorbic acid in liver. (PhSe)2 reversed the effects caused by clomazone in silver catfish, preventing increases in TBARS and protein carbonyl. Moreover, NPSH and ascorbic acid were increased by values near control. The results suggest that (PhSe)2 attenuated the oxidative damage induced by clomazone in silver catfish. The clomazone no caused an apparent situation of oxidative stress in carp, showing that this species is more resistant to this toxicant. Altogether, the containing (PhSe)2 diet helps fish to increase antioxidants defenses.

The effects of diphenyl diselenide on oxidative stress biomarkers in Cyprinus carpio exposed to herbicide quinclorac (Facet®).

The occurrence of pollutants in the aquatic environment can produce severe toxic effects on non-target organisms, including fish. These sources of contamination are numerous and include herbicides, which represent a large group of toxic chemicals. Quinclorac, an herbicide widely applied in agriculture, induces oxidative stress due to free radical generation and changes in the antioxidant defense system. The aim of this study was to assess if dietary diphenyl diselenide (PhSe)2 has a protective effect in tissues of fish species Cyprinus carpio exposed to the quinclorac herbicide. The fish were fed with either a standard or a diet containing 3.0 mg/Kg of diphenyl diselenide for 60 d. After were exposed to 1 mg/L of Facet® (quinclorac commercial formulation) for 192 h. At the end of the experimental period, parameters as thiobarbituric acid-reactive substance levels (TBARS), protein carbonyl, catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), nonprotein thiols (NPSH) and ascorbic acid in the liver, gills, brain and muscle were evaluated in Cyprinus carpio. In fish exposed to quinclorac and feeding with standard diet TBARS levels increased in liver and gills. However, SOD activity decreases in liver whereas no alterations were observed in catalase activity in this tissue. Quinclorac also decrease GST activity in liver and brain, NPSH in brain and muscle and ascorbic acid in muscle. Concerning protein carbonyl exposed to herbicide the fish did not show any alterations. The diphenyl diselenide supplemented diet reversed these effects, preventing increases in TBARS levels in liver and gills. GST activity was recovered to control values in liver. NPSH levels in brain and muscle increased remain near to control values. These results indicated that dietary diphenyl diselenide protects tissues against quinclorac induced oxidative stress ameliorating the antioxidant properties.