Increased incidence of hepatic insulin-sensitizing substance (HISS)-dependent insulin resistance in female rats prenatally exposed to ethanol

Insulin causes the release of the hepatic insulin-sensitizing substance (HISS) from the liver. Hepatic parasympathetic nerves play a permissive role in the release of HISS. HISS-dependent insulin resistance (HDIR) occurs in the absence of HISS. Fetal ethanol exposure has been shown to cause dose-dependent HDIR in adult male rat offspring. Since female offspring are more severely affected by in utero ethanol toxicity, we hypothesized that fetal alcohol exposure causes higher incidence and more severe HDIR in adult female offspring. Adult female rat offspring prenatally exposed to different concentrations of ethanol (0%, 15%, and 20%) were tested for insulin sensitivity using the rapid insulin sensitivity test (RIST). The RIST index was significantly reduced in the 15% (134.1 +/- 16.1 mg/kg) and the 20% (98.7 +/- 9.7 mg/kg) group compared with the 0% (220.9 +/- 27.6 mg/kg) group. Administration of atropine produced significant additional HDIR in the 15% group (82.9 +/- 14.5 mg/kg) but not the 20% group (83.8 +/- 20.5 mg/kg) indicating complete HDIR had been produced in this group, contrary to the adult male offspring in a previous study. The results are consistent with the hypothesis that adult-female offspring are more severely affected by in utero ethanol exposure compared with adult-male offspring.     

Role of carnosine in preventing thioacetamide-induced liver injury in the rat

Carnosine (beta-alanyl-L-histidine) is a dipeptide with antioxidant properties. Free radicals are involved in the pathogenesis of acute liver injury induced by thioacetamide (TAA). In this study, we investigated the effect of carnosine treatment on TAA-induced oxidative stress and hepatotoxicity. Rats were injected intraperitoneally with TAA (500 mg/kg) and carnosine (250 mg/kg, intraperitoneal) was co-administered with TAA. All animals were killed 24 h after injections. TAA administration resulted in hepatic necrosis, significant increases in plasma transaminase activities as well as hepatic lipid peroxide levels. In addition, hepatic antioxidant system was found to be depressed following TAA administration. When carnosine was co-administered with TAA in rats, plasma transaminase activities were found to approach to normal values in rats. Histological findings also suggested that carnosine has preventive effect on TAA-induced hepatic necrosis. Carnosine treatment caused significant decreases in lipid peroxide levels in TAA-treated rats without any changes in enzymatic and non-enzymatic antioxidants except vitamin E in the liver of rats. Our findings indicate that carnosine, in vivo may have a preventive effect on TAA-induced oxidative stress and hepatotoxicity by acting as an non-enzymatic antioxidant itself.     

Acute hemorrhage causes hepatic insulin sensitizing substance (HISS)-dependent insulin resistance

Hepatic insulin sensitizing substance (HISS) has been shown to account for 55% of the action of insulin in the fed state. HISS blockade leads to HISS-dependent insulin resistance (HDIR). The objective of this study was to test the hypothesis that insulin resistance produced by hemorrhage was HDIR. Insulin sensitivity was measured using the rapid insulin sensitivity test (RIST), which can identify HISS-dependent and independent components. Hemorrhage was performed in anesthetized rats by removing blood to reduce mean arterial pressure to 50 mmHg. Subsequent to blood removal, a RIST was performed. The results show that hemorrhage caused complete HDIR as subsequent administration of atropine failed to further reduce insulin sensitivity. However, the post-hemorrhage RIST was reduced by 34% and not the anticipated 55%. The lesser reduction of the RIST index by hemorrhage was related to reduced apparent volume of distribution and clearance of insulin, since occlusion of the superior mesenteric artery, which caused a similar decrease in portal venous flow as did hemorrhage, resulted in a similar degree of reduction of insulin clearance. The response to administered insulin was confounded by the impact of reduced hepatic blood flow on insulin metabolism that resulted in an increase in the HISS independent (direct) action of injected insulin against a background of complete HDIR. HDIR represents a useful hormonal response to assure a hyperglycemic response to hemorrhage.     

Comparison of melatonin, vitamin E and L-carnitine in the treatment of neuro- and hepatotoxicity induced by thioacetamide

This study was designed to evaluate and compare the effect of melatonin, vitamin E and L-carnitine on brain and liver oxidative stress and liver damage. Oxidative stress and hepatic failure were produced by a single dose of thioacetamide (TAA) (150 mg kg(-1)) in Wistar rats. A dose of either melatonin (3 mg kg(-1)) vitamin E (20 mg kg(-1) ) or L-carnitine (100 mg kg(-1)) was used. Blood samples were taken from the neck vasculature in order to determine ammonium, blood urea nitrogen (BUN) and liver enzymes. Lipid peroxidation products, glutathione (GSH) content and antioxidative enzymes were determined in cerebral and hepatic homogenates. The results showed a decrease in BUN and in the antioxidant enzymes activities and GSH in the brain and liver. Likewise, TAA induced significant enhancement of lipid peroxidation products levels in both liver and brain, as well as in ammonia values. Melatonin, vitamin E and L-carnitine, although melatonin more significantly, decreased the intensity of the changes produced by the administration of TAA alone. Furthermore melatonin combined with TAA, decreased the ammonia levels and increased the BUN values compared with TAA animals. Also it was more effective than vitamin E or L-carnitine in these actions. These data show the protective effect of these agents, especially melatonin, against oxidative stress and hepatic damage present in fulminant hepatic failure.     

Effects of shark hepatic stimulator substance on the function and antioxidant capacity of liver mitochondria in an animal model of acute liver injury

This study was carried out to investigate whether shark hepatic stimulator substance （HSS） can prevent acute liver injury and affect mitochondrial function and antioxidant defenses in a rat model of thioacetamide （TAA）-induced liver injury. The acute liver injury was induced by two intraperitoneal injections of TAA （400 mg/kg） in a 24 h interval. In the TAA plus shark HSS group, rats were treated with shark HSS （80 mg/kg） 1 h prior to each TAA injection. In this group, serum liver enzyme activities were significantly lower than those in the TAA group. The mitochondrial respiratory control ratio was improved, and the mitochondrial respiratory enzyme activities were increased in the TAA plus shark HSS group. The mitochondrial antioxidant enzyme activities and glutathione level were higher in the TAA plus shark HSS group than in the TAA group. These results suggest that the protective effect of shark HSS against TAA-induced acute liver injury may be a result of the restoration of the mitochondrial respiratory function and antioxidant defenses and decreased oxygen stress.     

S-adenosylmethionine (SAMe) protects against acute alcohol induced hepatotoxicity in mice small star, filled

Although S-Adenosylmethionine (SAMe) has beneficial effects in many hepatic disorders, the effects of SAMe on acute alcohol-induced liver injury are unknown. In the present study, we investigated effects of SAMe on liver injury in mice induced by acute alcohol administration. Male C57BL/6 mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. SAMe (5 mg/kg BW) was administrated i.p. once a day for three days before ethanol administration. Subsequent serum ALT level, hepatic lipid peroxidation, enzymatic activity of CYP2E1 and hepatic mitochondrial glutathione levels were measured colorimetrically. Intracellular SAMe concentration was measured by high-performance liquid chromatography (HPLC). Histopathological changes were assessed by H&E staining. Our results showed that acute ethanol administration caused prominent microvesicular steatosis with mild necrosis and an elevation of serum ALT activity. SAMe treatment significantly attenuated the liver injury. In association with the hepatocyte injury, acute alcohol administration induced significant decreases in both hepatic SAMe and mitochondrial GSH levels along with enhanced lipid peroxidation. SAMe treatment attenuated hepatic SAMe and mitochondrial GSH depletion and lipid peroxidation following acute alcohol exposure. These results demonstrate that SAMe protects against the liver injury and attenuates the mitochondrial GSH depletion caused by acute alcohol administration. SAMe may prove to be an effective therapeutic agent in many toxin-induced liver injuries including those induced by alcohol.     

Vitamin C - vitamin E interaction in juvenile lake sturgeon (Acipenser fulvescens R.), a fish able to synthesize ascorbic acid

The hypothesis that vitamin C interacts with vitamin E in vivo was investigated in juvenile lake sturgeon. Ten-month old lake sturgeon were fed diets supplemented with either 0 or 1250 mg ascorbic acid/kg diet concomitantly with either 0 or 200 mg α tocopherol/kg diet for 7 weeks at 17°C. Dietary vitamin C supplement resulted in significant increases of ascorbate concentrations in the posterior kidney and liver of sturgeon. Dietary vitamin E omission affected liver concentrations of α-tocopherol (10.0 ± 4.5 μg/g) in comparison to sturgeon fed a diet supplemented with vitamin E and vitamin C (99.5 ± 22.9 μg/g). Dietary vitamin C supplement decreased liver α-tocopherol concentration in vitamin E-deprived sturgeon. Also, vitamin E supplement lowered posterior kidney and liver ascorbic acid concentrations in vitamin C-deprived sturgeon. Gulonolactone oxidase and dehydroascorbic acid reductase activities were stimulated in groups fed vitamin C. Thiobarbituric acid-reactive substances concentrations (an indicator of lipid peroxidation) were higher in sturgeon fed either of vitamins as compared to sturgeon deprived of both vitamins. The results suggested that large doses of vitamins C and E may be prooxidant in vivo.     

Phospholipid Hydroperoxides and Lipid Peroxidation in Liver and Plasma of ODS Rats Supplemented with α-Tocopherol and Ascorbic Acid

Forty-five mutant male ODs rats, unable to synthesize ascorbic acid, were fed nine diets containing 5, 50 or 250 mg of vitamin E/kg diet and 150,300 or 900 mg of vitamin C/kg diet for 21 days. The concentrations of vitamins C and E increased in liver and plasma in relation to the level of these vitamins in the diet. Vitamin C dietary supplementation increased the plasma vitamin E content at low levels of vitamin E intake, supporting the concept of an in vivo synergism between both antioxidant vitamins. Vitamin C, at the dietary levels studied, did not affect the lipid peroxidation. Vitamin E decreased liver and plasma endogenous levels of thiobarbituric acid-reactive substances and liver sensitivity to non-enzymatic lipid peroxidation. This was confirmed by a highly specific assay of lipid hydroperoxides using high performance liquid chromatography with chemiluminescence detection. The hepatic concentration of both phosphatidylcholine and phosphatidylethanolamine hydroperoxides decreased as the vitamin E content of the diet increased. The results show for the first time the capacity of vitamin E to protect against peroxidation of major phospho-lipids in vivo under basal unstressed conditions.     

Insulin sensitivity regulated by feeding in the conscious unrestrained rat

Hepatic insulin sensitizing substance (HISS), a putative hormone released from the liver in response to insulin in fed animals, accounts for 50-60% of insulin action. HISS release is regulated by permissive control of the hepatic parasympathetic nerves. The objectives were to develop the rapid insulin sensitivity test (RIST) in conscious rats, and to assess the effects of anesthesia, atropine, feeding, and fasting on insulin action. The RIST index, expressed as milligrams glucose per kilogram body weight required to maintain euglycemia after a 50 mU/kg bolus of insulin, was similar in conscious and anesthetized rats (238.6+/-42.5 vs. 225.3+/-30.4 mg/kg). Atropine produced a 56% inhibition of insulin action in fed rats. After a 24 h fast, full HISS-dependent insulin resistance had developed as shown by a low RIST index that was not reduced further by atropine. Fasting caused a 10.5% decrease in insulin action per hour over six hours. HISS-dependent insulin resistance in 24-h fasted rats was reversed 4 h after re-feeding (90.9+/-12.3 vs. 204.5+/-30.5 mg/kg). We conclude that HISS-dependent and HISS-independent insulin action, as assessed by the RIST, is similar in conscious and pentobarbital-anesthetized rats. Pharmacological blockade of HISS-dependent insulin action and physiological regulation of HISS action by feeding-fasting is confirmed. Re-feeding fasted rats reversed HISS-dependent insulin resistance. Merits of use of the RIST in conscious versus anesthetized rats are discussed.     

Vitamins C and E improve rat embryonic antioxidant defense mechanism in diabetic culture medium.

BACKGROUND: Diabetes teratogenicity seems to be related to embryonic oxidative stress and the extent of the embryonic damage can apparently be reduced by antioxidants. We have studied the mechanism by which antioxidants, such as vitamins C and E, reduce diabetes-induced embryonic damage. We therefore compared the antioxidant capacity of 10.5-day-old rat embryos and their yolk sacs cultured for 28h in diabetic culture medium with or without vitamins C and E. METHODS: The embryos were cultured in 90% rat serum to which 2mg/ml glucose, 2mg/ml beta hydroxy butyrate (BHOB) and 10 microg/ml of acetoacetate were added. Rat embryos were also cultured in a diabetic medium with 25 microg/ml of vitamin E and 50 microg/ml of vitamin C. Control embryos were cultured in normal rat serum with or without vitamins C and E. RESULTS: Decreased activity of Cu/Zn superoxide dismutase (SOD) and of catalase (CAT) in the "diabetic" embryos and their yolk sacs, and reduced concentrations of low molecular weight antioxidant (LMWA) were found. Under these conditions we also found a decrease in vitamin C and vitamin E concentrations in the embryos, as measured by HPLC. In situ hybridization for SOD mRNA showed a marked reduction of SOD mRNA in the brain, spinal cord, heart and liver of embryos cultured in diabetic medium in comparison to controls. Following the addition of vitamins C and E to the diabetic culture medium, SOD and CAT activity, the concentrations of LMWA, the levels of vitamin C and E and the expression of SOD mRNA in the embryos and yolk sacs returned to normal. CONCLUSIONS: Diabetic metabolic factors seem to have a direct effect on embryonic SOD gene and perhaps genes of other antioxidant enzymes, reducing embryonic endogenous antioxidant defense mechanism. This in turn may cause a depletion of the LMWA, such as vitamins C and E. The addition of these vitamins normalizes the embryonic antioxidant defense mechanism, reducing the damage caused by the diabetic environment.     

Effect of histidine on autotaxin activity in experimentally induced liver fibrosis

The aim of this study was to explain whether serum autotaxin (ATX) activity might be a target for regulation of liver fibrosis and to evaluate the hepatoprotective and antifibrotic effects of histidine in thioacetamide (TAA)-induced liver fibrosis in rats. This study was carried out on 100 Wistar Albino rats, classified into five groups, each containing 20 rats: Group I (control group), Group II: rats were given histidine intraperitoneally, Group III: rats were injected intraperitoneally with TAA, Group IV: rats were injected with L-histidine together with TAA, and Group V: rats were injected with TAA for 1 month then treated with intraperitoneal injection of L-histidine for another month. At the end of experiment, blood and liver were collected for determination of some liver enzymes, plasma total antioxidant capacity (TAC), serum ATX activity, and liver tissue hydroxyproline. Thioacetamide treatment caused significant increases in liver enzymes, ATX activities, and liver hydroxyproline, but a significant decrease in plasma's TAC. Upon treatment with histidine, a significant decrease in liver enzymes, ATX activities, and liver hydroxyproline was observed with a significant increase in plasma TAC in Group IV and a significant decrease in Group V. Histidine as an antioxidant has a protective effect on TAA-induced liver fibrosis; it is beneficial in rats not only by inhibition of collagen synthesis and increasing TAC but also by inhibition of ATX activities thus reducing its capacity to produce lysophosphatidic acid, which has a role in liver fibrosis.     

Vitamins E and C ameliorate the oxidative stresses induced by zinc oxide nanoparticles on liver and gills of Oreochromis niloticus

The current study evaluated the hazards of Zinc oxide nanoparticles (ZnONPs) on Nile Tilapia liver and gill antioxidants enzymes activities and antioxidants genes expressions. The ameliorative action of vitamins E and C mixture was investigated. Two hundred males of Nile Tilapia were exposed to one and two mg?L^?1 of ZnONPs either with or without vitamin C and E mixture for 7 and 15?days. Glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities and gene expression as well glutathione (GSH) and lipid peroxide (LPO) levels were investigated. The results revealed that the exposure to ZnONPs could induce alterations in the liver and gills antioxidants and LPO of Nile Tilapia. Moreover, the mixture of vitamin E and C highly effective in alleviation the toxic effect of ZnONPs.     

Finasteride Has Regionally Different Effects on Brain Oxidative Stress and Acetylcholinesterase Activity in Acute Thioacetamide-Induced Hepatic Encephalopathy in Rats

Finasteride (FIN) inhibits neurosteroid synthesis and potentially improves the course of hepatic encephalopathy (HE). This study aimed to investigate the effects of FIN on brain oxidative stress and acetylcholinesterase (AchE) activity in acute thioacetamide-induced HE in rats. Male Wistar rats were divided into groups: 1. control; 2. thioacetamide-treated group (TAA; 900 mg/kg); 3. finasteride-treated group (FIN; 150 mg/kg); 4. group treated with FIN and TAA (FIN+TAA). Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered intraperitoneally during three days and in FIN+TAA group FIN was administered 2h before every dose of TAA. FIN pretreatment prevented TAA-induced rise in malondialdehyde level in the cortex due to restoration of catalase activity and increased expression of superoxide dismutase 1 (SOD1) and induced an increase in malondialdehyde level in the thalamus due to reduction of glutathione peroxidase (GPx) and glutathione reductase (GR) activity. Although FIN pretreatment did not affect malondialdehyde level in hippocampus and caudate nucleus, hippocampal SOD1 expression was higher (p<0.05) and GR activity lower in FIN+TAA vs. TAA group (p<0.05). GPx activity was lower in caudate nucleus in FIN+TAA vs. TAA group (p<0.01). FIN pretreatment prevented TAA-induced rise in AchE activity in the thalamus and caudate nucleus and AchE activity correlates inversely in the thalamus (p<0.05) and positively in caudate nucleus (p<0.01) with malondialdehyde level. FIN has regionally selective effects on oxidative stress and AchE activity in the brain in acute TAA-induced HE in rats. The prooxidant role of FIN in the thalamus may be causally linked with inhibition of AchE.     

Insulin sensitivity is mediated by the activation of the ACh/NO/cGMP pathway in rat liver

The hepatic parasympathetic nerves and hepatic nitric oxide synthase (NOS) are involved in the secretion of a hepatic insulin sensitizing substance (HISS), which mediates peripheral insulin sensitivity. We tested whether binding of ACh to hepatic muscarinic receptors is an upstream event to the synthesis of nitric oxide (NO), which, along with the activation of hepatic guanylate cyclase (GC), permits HISS release. Male Wistar rats (8-9 wk) were anesthetized with pentobarbital sodium (65 mg/kg). Insulin sensitivity was assessed using a euglycemic clamp [the rapid insulin sensitivity test (RIST)]. HISS inhibition was induced by antagonism of muscarinic receptors (atropine, 3 mg/kg i.v.) or by blockade of NOS [NG-nitro-L-arginine methyl ester (L-NAME), 1 mg/kg intraportally (i.p.v.)]. After the blockade, HISS action was tentatively restored using a NOdonor [3-morpholynosydnonimine (SIN-1), 5-10 mg/kg i.p.v.] or ACh (2.5-5 microg.kg(-1).min(-1) .i.p.v.). SIN-1 (10 mg/kg) reversed the inhibition caused by atropine (RIST postatropine 137.7 +/- 8.3 mg glucose/kg; reversed to 288.3 +/- 15.5 mg glucose/kg, n = 6) and by L-NAME (RIST post-L-NAME 152.2 +/- 21.3 mg glucose/kg; reversed to 321.7 +/- 44.7 mg glucose/kg, n = 5). ACh did not reverse HISS inhibition induced by L-NAME. The role of GC in HISS release was assessed using 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 nmol/kg i.p.v.), a GC inhibitor that decreased HISS action (control RIST 237.6 +/- 18.6 mg glucose/kg; RIST post-ODQ 111.7 +/- 6.2 mg glucose/kg, n = 5). We propose that hepatic parasympathetic nerves release ACh, leading to hepatic NO synthesis, which activates GC, triggering HISS action.     

Influence of dietary vitamin E and C supplementation on vitamin E and C content and thiobarbituric acid reactive substances (TBARS) in different tissues of growing pigs

To investigate the influence and possible interactions of dietary vitamin E and C supplementation on vitamin content of both vitamins and oxidative stability of different pork tissues 40 Large White barrows from 25 kg to 106 kg were allocated to four different cereal based diets: Basal diet (B), dl-alpha-tocopherylacetate + 200 mg/kg (E), crystalline ascorbic acid + 300 mg/kg (C) or both vitamins (EC). At slaughtering samples of liver, spleen, heart, kidney, backfat outer layer, ham and M. tongissimus dorsi were obtained. Growth performance of the pigs and carcass characteristics were not influenced by feeding treatments. Dietary vitamin E supplementation had a significant effect on the vitamin E and alpha-tocopherol concentration in all investigated tissues. Backfat outer layer, liver, spleen, kidney and heart had higher vitamin E concentrations than ham and M. longissimus dorsi. Dietary vitamin C supplementation tended towards enhanced vitamin E levels except for ham samples. Therefore, some synergistic actions without dietary vitamin E supplementation between the two vitamins could be shown. The vitamin C concentration and TBARS were increased or at least equal in all tissues due to vitamin C supplementation. Dietary alpha-tocopherol supplementation resulted in lower TBARS in backfat outer layer (malondialdehyde 0.35 mg/kg in B vs. 0.28 mg/kg in E), but increased in heart and ham. When both vitamins were supplemented (EC) TBARS were lower in M. longissimus dorsi and backfat outer layer, equal in heart and higher in liver and ham compared to a single vitamin C supplementation. Rancimat induction time of backfat outer layer was 0.3 h higher in C compared to B and 0.17 h higher in EC than in E. Correlations between levels of both vitamins were positive for kidney (r = 0.169), M. longissimus dorsi (r = 0.499) and ham (r = 0.361) and negative for heart (r = -0.350). In liver and spleen no interaction could be found. In backfat outer layer vitamin E was positively correlated with rancimat induction time (r = 0.550) and negatively with TBARS (r = -0.202), but provided no evidence that dietary vitamin E supply led to better oxidative stability.     

The effects of some antioxidant vitamin- and trace element-supplemented diets on activities of SOD, CAT, GSH-Px and LPO levels in chicken tissues

The effect of diets containing antioxidant vitamins and trace elements on chicken tissue activities of SOD, CAT, GSH-Px and of LPO levels was investigated. Chickens, 45 weeks of age were divided into six groups: control group, Cu group (13.2 mg Cu kg(-1) diet); Se group (0.07 mg Se kg(-l) diet); vitamin E group (70 mg DL-alpha-tocopherol acetate kg(-1) diet) and a constant level vitamin C, 200 mg kg(-1) diet); vitamin A group (240 mg retinol acetate kg(-1) diet) and vitamin C group (500 mg ascorbic acid kg(-1) diet). Significant variation of these antioxidant enzyme activities and LPO levels according to gender was demonstrated statistically. In the Cu group, CuZnSOD activity in the liver, erythrocyte, kidney and heart significantly increased by 75, 40, 12, 12% respectively (P<0.05). MnSOD activity in the heart, liver, kidney and brain of the vitamin C and in the heart of Cu group were found to be increased by approximately 15%, while in liver tissue of the Cu group it was reduced by 19% (P<0.05). GSH-Px activities in the Se, vitamin E and C groups were significantly increased, conversely LPO levels decreased (P<0.001). CAT activities in the liver and heart of the vitamin C group were significantly decreased (by 32%), but in kidney tissue only that of the Cu group was increased from 30.2 +/- 4.767 to 144.49 +/- 6.93 U mg(-1) P<0.001. The resistance to stress of the vitamin E and C groups, which had significantly increased activities of antioxidant enzymes and decreased lipid peroxide levels, were determined in 60% moisture medium at 45 degrees C.     

Normal adaptations to exercise despite protection against oxidative stress

It has been reported that supplementation with the antioxidant vitamins C and E prevents the adaptive increases in mitochondrial biogenesis and GLUT4 expression induced by endurance exercise. We reevaluated the effects of these antioxidants on the adaptive responses of rat skeletal muscle to swimming in a short-term study consisting of 9 days of vitamins C and E with exercise during the last 3 days and a longer-term study consisting of 8 wk of antioxidant vitamins with exercise during the last 3 wk. The rats in the antioxidant groups were given 750 mg·kg body wt(-1)·day(-1) vitamin C and 150 mg·kg body wt(-1)·day(-1) vitamin E. In rats euthanized immediately after exercise, plasma TBARs were elevated in the control rats but not in the antioxidant-supplemented rats, providing evidence for an antioxidant effect. In rats euthanized 18 h after exercise there were large increases in insulin responsiveness of glucose transport in epitrochlearis muscles mediated by an approximately twofold increase in GLUT4 expression in both the short- and long-term treatment groups. The protein levels of a number of mitochondrial marker enzymes were also increased about twofold. Superoxide dismutases (SOD) 1 and 2 were increased about twofold in triceps muscle after 3 days of exercise, but only SOD2 was increased after 3 wk of exercise. There were no differences in the magnitudes of any of these adaptive responses between the control and antioxidant groups. These results show that very large doses of antioxidant vitamins do not prevent the exercise-induced adaptive responses of muscle mitochondria, GLUT4, and insulin action to exercise and have no effect on the level of these proteins in sedentary rats.     

Influence of diets supplemented with vitamins C and E on pirarucu (Arapaima gigas) blood parameters

This study evaluated the influence of diets supplemented with 500, 800, 1200 mg kg-1 of vitamin C (ascorbic acid or AA) and vitamin E (alpha-tocopherol or alpha-T) on the physiological responses of pirarucu fed for 2 months. Weight and mortality were not affected by dietary vitamin type or their concentrations. Significant increase (p<0.05) on the red blood cells count was obtained on treatments with 800 and 1200 mg AA kg-1 and on the hemoglobin concentration on treatment with 500 mg alpha-T kg-1 relatively to control. Mean corpuscular volume presented a significant decrease (p<0.05) on treatment with 800 and 1200 mg AA kg-1 when compared to control. Mean corpuscular hemoglobin concentration was significantly high (p<0.05) on treatment with 500 mg alpha-T kg-1. Only in vitamin C treatments, we noticed a significant increase (p<0.05) in the number of leucocytes relative to control. All fish in the vitamin-supplemented treatments, except 500 mg AA kg-1, had high total protein values compared to control. Fish treated with 800 or 1200 mg alpha-T kg-1 also showed increases in plasma glucose concentrations. Our results suggest that 800 and 1200 mg AA kg-1 are probably the most suitable concentrations for pirarucu diets, although high vitamin E diets are not necessary for quantitative leucocyte increases for this species.     

Protective antioxidant effect of vitamins C and E in streptozotocin induced diabetic rats

We have investigated the protective effect of vitamin C and E together supplementation on oxidative stress and antioxidant enzyme activities in the liver of streptozotocin-induced diabetic rats, unsupplemented diabetic and control rats. We also determined the levels of both the vitamins and oxidative stress in plasma. Vitamin supplementation in diabetic rats lowered plasma and liver lipid peroxidation, normalised plasma vitamin C levels and raised vitamin E above normal levels. In liver, the activity of glutathione peroxidase was raised significantly and that of glutathione-S-transferase was normalised by vitamin supplementation in diabetic rats. The levels of lipid peroxidation products in plasma and liver of vitamin-supplemented diabetic rats and activities of antioxidant enzymes in liver suggest that these vitamins reduce lipid peroxidation by quenching free radicals.     

Pattern of insulin delivery affects hepatic insulin sensitizing substance (HISS) action and insulin resistance

Hepatic insulin sensitizing substance (HISS) action accounts for 55% of the glucose disposal effect of a bolus of insulin in the fed state. To determine the effect of continuous versus pulsatile insulin delivery on HISS action in male Sprague-Dawley rats, insulin sensitivity was assessed using the rapid insulin sensitivity test (RIST) before and after a continuous, pulsatile, or bolus insulin (60 mU/kg i.v.) delivery. There was a significant difference in the RIST index after a continuous insulin infusion (247.9 mg/kg before, 73.2 mg/kg after) but not after 3 pulses where insulin action returned to baseline between pulses (211.6 mg/kg before, 191.0 mg/kg after) or single bolus (205.8 mg/kg before, 189.9 mg/kg after) insulin infusion. If a 3-pulse infusion was timed so that insulin action did not return to baseline between pulses, HISS action was suppressed. Continuous insulin infusion (10-30 min) showed progressive postinfusion blockade of HISS action. To maintain HISS-dependent insulin action, continuous insulin infusions should be avoided.