Exogenously-Sourced Ethylene Positively Modulates Photosynthesis, Carbohydrate Metabolism, and Antioxidant Defense to Enhance Heat Tolerance in Rice.

The effect of exogenously-applied ethylene sourced from ethephon (2-chloroethyl phosphonic acid)was studied on photosynthesis, carbohydrate metabolism, and high-temperature stress tolerance in Taipei-309 and Rasi cultivars of rice (Oryza sativa L.). Heat stress increased the content of H2O2 and thiobarbituric acid reactive substances (TBARS)more in Rasi than Taipei-309. Further, a significant decline in sucrose, starch, and carbohydrate metabolism enzyme activity and photosynthesis was also observed in response to heat stress. The application of ethephon reduced H2O2 and TBARS content by enhancing the enzymatic antioxidant defense system and improved carbohydrate metabolism, photosynthesis, and growth more conspicuously in Taipei-309 under heat stress. The ethephon application enhanced photosynthesis by up-regulating the psbA and psbB genes of photosystem II in heat-stressed plants. Interestingly, foliar application of ethephoneffectively down-regulated high-temperature-stress-induced elevated ethylene biosynthesis gene expression. Overall, ethephon application optimized ethylene levels under high-temperature stress to regulate the antioxidant enzymatic system and carbohydrate metabolism, reducing the adverse effects on photosynthesis. These findings suggest that ethylene regulates photosynthesis via carbohydrate metabolism and the antioxidant system, thereby influencing high-temperature stress tolerance in rice.

Synthesis, Molecular Modeling and Biological Evaluation of 5-arylidene-N,N-diethylthiobarbiturates as Potential α-glucosidase Inhibitors.

BACKGROUND: Barbituric acid derivatives are a versatile group of compounds which are identified as potential pharmacophores for the treatment of anxiety, epilepsy and other psychiatric disorders. They are also used as anesthetics and have sound effects on the motor and sensory functions. Barbiturates are malonylurea derivatives with a variety of substituents at C-5 position showing resemblance with nitrogen and sulfur containing compounds like thiouracil which exhibited potent anticancer and antiviral activities. Recently, barbituric acid derivatives have also received great interest for applications in nanoscience. OBJECTIVE: Synthesis of 5-arylidene-N,N-diethylthiobarbiturates, biological evaluation as potential α-glucosidase inhibitors and molecular modeling. METHODS: In the present study, N,N-Diethylthiobarbituric acid derivatives were synthesized by refluxing of N,N-diethylthiobarbituric acid and different aromatic aldehydes in distilled water. In a typical reaction; a mixture of N,N-diethylthiobarbituric acid 0.20 g (1 mmol) and 5-bromo-2- hydroxybenzaldehyde 0.199 g (1 mmol) mixed in 10 mL distilled water and reflux for 30 minutes. After completion of the reaction, the corresponding product 1 was filtered and dried and yield calculated. It was crystallized from ethanol. The structures of synthesized compounds 1-25 were carried out by using 1H, 13C NMR, EI spectroscopy and CHN analysis used for the determination of their structures. The α-glucosidase inhibition assay was performed as given by Chapdelaine et al., with slight modifications and optimization. RESULTS: Our newly synthesized compounds showed a varying degree of α-glucosidase inhibition and at least four of them were found as potent inhibitors. Compounds 6, 5, 17, 11 exhibited IC50 values (Mean±SEM) of 0.0006 ± 0.0002, 18.91 ± 0.005, 19.18 ± 0.002, 36.91 ± 0.003 µM, respectively, as compared to standard acarbose (IC50, 38.25 ± 0.12 µM). CONCLUSION: Our present study has shown that compounds 6, 5, 17, 11 exhibited IC50 values of 0.0006 ± 0.0002, 18.91 ± 0.005, 19.18 ± 0.002, 36.91 ± 0.003 µM, respectively. The studies were supported by in silico data analysis.

Antidiabetic, Antihyperlipidemic, and Antioxidant Activities of Mulberry Lees Fermented Products in Diabetic Mice.

Mulberry lees are the sediment in the bottom of the barrel, which can be obtained from the processing of mulberry wine, and they are considered as low-value byproducts. In this study, mulberry lees were extracted with ethanol, and then fermented with Monascus pilosus to obtain fermented products (M × M). Male ICR mice were diabetes induced by STZ, and then oral administration of fermented products. The results showed that fermented products could reduce 31.9% to 47.9% plasma glucose, 25.8% to 48.2% total cholesterol, and 16.7% to 25% triglyceride levels in diabetic mice, and it can greatly lower the malondialdehyde (MDA) content by 26.4% to 59.7% but raise antioxidant enzyme activity in the liver of the mice. Moreover, fermented products not only could reduce AST and ALT activity of the diabetic mice, thereby alleviating liver inflammation, but also lowered the urea nitrogen and creatinine levels, improved glomerulus volume, and reduced swelling and inflammation in the kidneys. It was concluded that mulberry lees fermented products could be served as a value-added resource for human health.

Effect of lithocholic acid on biologically active α,ß-unsaturated aldehydes induced by H2O2 in glioma mitochondria for use in glioma treatment.

Lithocholic acid (LCA) is known to kill glioma cells while sparing normal neuronal cells. However, the anti-glioma mechanism of LCA is unclear at present. Although malondialdehyde (MDA) is not specific to detect tumors, biologically active α,ß-unsaturated aldehydes can be used to detect the outcome of gliomas, especially the mitochondria, as a research tool. The purpose of this research was to determine the optimum conditions for a lipid peroxidation model, according to changes in the aldehydes formed from the reaction between 2-thiobarbituric acid and biologically active α,ß-unsaturated aldehydes. Experimental methods and procedures were successfully established for a model of lipid peroxidation induced by H2O2 in glioma mitochondria for glioma treatment and optimum conditions for LCA treatment were determined. The optimal conditions for the model were a glioma mitochondrial concentration of 1.5 mg/ml, H2O2 concentration of 0.3 mg/ml, duration of action of 30 min, and addition of 4.0 ml of 46 mM thiobarbituric acid. The effect of LCA, as determined by changes in the UV peaks at 450, 495, and 532 nm, was optimal at a concentration of 100 µM, a duration of action of 15 min, and in an acidic microenvironment. The study concluded that a suitable concentration of LCA has anti-glioma effects as determined by the effect on changes in the UV peaks at 450, 495 and 532 nm and the mitochondrial model developed should be conducive to further in-depth research.

Chinese olive extract ameliorates hepatic lipid accumulation in vitro and in vivo by regulating lipid metabolism.

Chinese olive contains plenty of polyphenols, which possess a wide range of biological actions. In this study, we aimed to investigate the role of the ethyl acetate fraction of Chinese olive fruit extract (CO-EtOAc) in the modulation of lipid accumulation in vitro and in vivo. In cellular studies, CO-EtOAc attenuated oleic acid-induced lipid accumulation; we then elucidated the molecular mechanisms of CO-EtOAc in FL83B mouse hepatocytes. CO-EtOAc suppressed the mRNA levels of fatty acid transporter genes (CD36 and FABP) and lipogenesis genes (SREBP-1c, FAS, and ACC1), but upregulated genes that govern lipolysis (HSL) and lipid oxidation (PPARα, CPT-1, and ACOX). Moreover, CO-EtOAc increased the protein expression of phosphorylated AMPK, ACC1, CPT-1, and PPARα, but downregulated the expression of mature SREBP-1c and FAS. AMPK plays an essential role in CO-EtOAc-mediated amelioration of lipid accumulation. Furthermore, we confirmed that CO-EtOAc significantly inhibited body weight gain, epididymal adipose tissue weight, and hepatic lipid accumulation via regulation of the expression of fatty acid transporter, lipogenesis, and fatty acid oxidation genes and proteins in C57BL/6 mice fed a 60% high-fat diet. Therefore, Chinese olive fruits may have the potential to improve the metabolic abnormalities associated with fatty liver under high fat challenge.

Temporal changes in plasma markers of oxidative stress following laparoscopic sleeve gastrectomy in subjects with impaired glucose regulation.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity and associated metabolic complications. Obesity and type 2 diabetes are associated with increased oxidative stress. Previous studies have examined changes in plasma oxidative stress after laparoscopic Roux-en-Y gastric bypass, but there is limited evidence of the effects of LSG. OBJECTIVES: To examine the effects of LSG on plasma thiobarbituric acid reactive substances (TBARS) and total antioxidant status (TAOS) at 1 and 6 months after LSG in patients with obesity and impaired glucose regulation. SETTING: University hospital, United Kingdom. METHODS: Twenty-two participants with impaired glucose homeostasis undergoing LSG (body mass index 50.1 kg/m2, glycated hemoglobin 53 mmol/mol) were studied. Measurements of fasting and 120-minute TBARS and TAOS were performed during an oral glucose tolerance test preoperatively and postoperatively. RESULTS: Compared with preoperative levels, significant decreases were seen 6 months postoperatively in fasting TBARS (61.0±17.9 versus 39.4±13.8 ng/mL, P = .04) and 120-minute TBARS (76.0±29.5 versus 46.5±16.3 ng/mL, P = .02). No significant changes were observed in plasma TAOS. No significant association was observed between changes in TBARS and other clinical or biochemical measures. CONCLUSION: We observed a significant reduction in TBARS, a global measure of lipid peroxidation 6 months after LSG in participants with obesity and impaired glucose regulation.

Hepatic oxidative stress and metal subcellular partitioning are affected by selenium exposure in wild yellow perch (Perca flavescens).

Yellow perch (Perca flavescens) collected from 11 lakes in the Canadian mining regions of Sudbury (Ontario) and Rouyn-Noranda (Quebec) display wide ranges in the concentrations of cadmium (Cd), nickel (Ni), selenium (Se), and thallium (Tl) in their livers. To determine if these trace elements, as well as copper (Cu) and zinc (Zn), are causing oxidative stress in these fish, we measured three biochemical indicators (glutathione (GSH), glutathione disulfide (GSSG) and thiobarbituric acid-reactive substances (TBARS)) in their livers. We observed that 44% of the yellow perch that we collected were at risk of cellular oxidative stress and lipid peroxidation. Considering all fish from all lakes, higher liver Se concentrations were coincident with both lower proportions of GSSG compared to GSH and lower concentrations of TBARS, suggesting that the essential trace-element Se acts as an antioxidant. Furthermore, fish suffering oxidative stress had higher proportions of Cd, Cu and Zn in potentially sensitive subcellular fractions (organelles and heat-denatured proteins) than did fish not suffering from stress. This result suggests that reactive oxygen species may oxidize metal-binding proteins and thereby reduce the capacity of fish to safely bind trace metals. High Cd concentrations in metal-sensitive subcellular fractions likely further exacerbate the negative effects of lower Se exposure.

VPO1 mediates oxidation of LDL and formation of foam cells.

Deposition of oxidized-LDL in vascular walls is essential in the initiation of atherosclerosis. Oxidation of LDL has been attributed to myeloperoxidase as its generation of potent oxidants. However, the exact mechanism of LDL oxidation and foam cell formation in atherosclerosis remains to be elucidated. Vascular peroxidase-1 (VPO1), a newly-identified heme-containing peroxidase, is primarily expressed in cardiovascular systems, and secreted into the circulation. The present study evaluates VPO1-mediated LDL oxidation and its role in atherosclerosis. VPO1 was first demonstrated binding to LDL. VPO1-mediated oxidation of proteins and lipids in LDL was verified by a variety of methods including immunoblot analysis, free tryptophan assay, UV absorbance, and thiobarbituric acid assay. VPO1-oxidized LDL caused accumulation of LDL in monocyte-like cells and promoted formation of foam cells. Administration of inflammation factors, LPS or TNF-α, induced increasing expression of VPO1 in aorta and secretion to plasma. TNF-α also promoted formation and retention of VPO1-oxidized LDL in aortic walls. Our data suggest that VPO1 contributes to oxidation and retention of LDL in vessel walls, and formation foam cells, indicating VPO1 as a novel potential mediator of atherosclerosis.

Evaluation of edaravone against radiation-induced oral mucositis in mice.

Oral mucositis induced by radiotherapy for cancers of the head and neck reduce the quality of life of patients. However, effective therapeutic agents are lacking. Symptomatic treatment involves local anesthesia and analgesia. We focused on the antioxidant effects of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; Radicut(®)). Oral mucositis was induced on the tongue tips of mice using a single dose of X-rays (20 Gy). To evaluate the protective effect of edaravone (30 and 300 mg/kg), administration was carried out 30 min before irradiation. Survival, oral mucositis score, myeloperoxidase activity, and levels of 2-Thiobarbituric acid reactive substances were measured, and all were improved compared with those of control mice. A significant difference was not found in terms of survival due to edaravone. Histopathologic findings also highlighted the beneficial features of edaravone. Edaravone reduced the production of reactive oxygen species. These findings suggest that the protective effect of edaravone against radiation-induced oral mucositis is through an antioxidant effect.

Effects of intermittent fasting on age-related changes on Na,K-ATPase activity and oxidative status induced by lipopolysaccharide in rat hippocampus.

Chronic neuroinflammation is a common characteristic of neurodegenerative diseases, and lipopolysaccharide (LPS) signaling is linked to glutamate-nitric oxide-Na,K-ATPase isoforms pathway in central nervous system (CNS) and also causes neuroinflammation. Intermittent fasting (IF) induces adaptive responses in the brain that can suppress inflammation, but the age-related effect of IF on LPS modulatory influence on nitric oxide-Na,K-ATPase isoforms is unknown. This work compared the effects of LPS on the activity of α1,α2,3 Na,K-ATPase, nitric oxide synthase gene expression and/or activity, cyclic guanosine monophosphate, 3-nitrotyrosine-containing proteins, and levels of thiobarbituric acid-reactive substances in CNS of young and older rats submitted to the IF protocol for 30 days. LPS induced an age-related effect in neuronal nitric oxide synthase activity, cyclic guanosine monophosphate, and levels of thiobarbituric acid-reactive substances in rat hippocampus that was linked to changes in α2,3-Na,K-ATPase activity, 3-nitrotyrosine proteins, and inducible nitric oxide synthase gene expression. IF induced adaptative cellular stress-response signaling pathways reverting LPS effects in rat hippocampus of young and older rats. The results suggest that IF in both ages would reduce the risk for deficits on brain function and neurodegenerative disorders linked to inflammatory response in the CNS.

Effects of probiotic supplementation on systemic and intestinal oxidant-antioxidant events in splenectomized rats.

PURPOSE: The objective of this study was to show the effects of probiotic supplementation on systemic and intestinal oxidant-antioxidant events in splenectomized rats. METHODS: Male rats were divided into control (group 1) and splenectomized (group 2) groups, and after splenectomy, some rats were given Lactobacillus delbruckii subsp. bulgaricus (highest amount of extracellular polysaccharides, 211 mg/l) for 7 days (group 3) or were given the treatment for 7 days before and 7 days after splenectomy (group 4). The plasma and small intestine tissue thiobarbituric acid reactive substances (TBARS), sulfhydryl group, glutathione, ascorbic acid, and nitric oxide metabolites (NO x ) levels were determined by a spectrophotometer. RESULTS: We found increased TBARS levels in both the plasma and small intestine in the splenectomized rats compared to controls. L. delbruckii subsp. bulgaricus supplementation decreased the TBARS levels in the plasma in the splenectomized rats. In this study, the plasma TBARS and NO x levels were decreased by L. delbruckii subsp. bulgaricus supplementation after or both after and before splenectomy (groups 3 and 4). CONCLUSIONS: Together, these data suggest that. L. delbruckii subsp. bulgaricus supplementation is beneficial for decreasing lipid peroxidation and enhancing the antioxidant capacity of systemic and intestinal tissue in splenectomized rats.

Quantification of malondialdehyde by HPLC-FL - application to various biological samples.

Malondialdehyde (MDA) is stabile product of lipid peroxidation (LPO), and therefore MDA is frequently used as a biomarker of LPO. To determine MDA level in various biological samples (human plasma, fish liver tissue and cells in culture), we used an HPLC method with fluorescent detection based on 2-thiobarbituric acid (TBA) assay. The method was validated by the use of spiked pooled plasma samples. In tested concentration range (0.15-3.0 µmol/L) the method was linear (R(2) = 0.9963), the between-day variability (coefficient of variations, CVs) was between 4.7 and 7.6%, the within-day variability CVs was between 2.6 and 6.4% and recovery was between 91.2 and 107.6%. The level of MDA in human plasma (healthy male, non-smokers, 46.3 ± 4.7 years; N = 38) was 2.2 ± 1.4 µmol/L; that in liver tissue of common carp (Cyprinus carpio; N = 12) was 0.02 ± 0.004 µmol/g tissue, and in cultured cells (human laryngeal carcinoma cells; N = 10) it was 0.18 ± 0.02 nmol/mg proteins. The HPLC-FL method is rapid, accurate and reliable to follow the extent of LPO in various biological samples, particularly in samples in which a low level of MDA is expected, such as cells in culture. Owing to the rapid analytical process and run time, it can be used for routine analysis of MDA in clinical laboratory.

[The ROS-generating and antioxidant systems in the liver of rats treated with prednisolone and vitamin D3].

The mechanisms of glucocorticoid-induced disturbances of liver function is currently not fully clarified. Vitamin D3 was previously shown to play an important role in the regulation of impaired oxidative metabolism and detoxification function of the liver associated with the effects of hepatotoxic compounds. The study was undertaken to define the intensity of oxidative metabolism in the rat liver and survival of hepatocytes after prolonged prednisolone administration and to assess whether vitamin D3 is capable to counter glucocorticoid-induced changes. It has been shown that prednisolone (0.5 mg per animal for 30 days) leads to 1.6-fold increase in the percentage of necrotic cells among isolated hepatocytes as compared with the control. The glucocorticoid-induced impairment of hepatocellular function was accompanied by enhanced generation of reactive oxygen species (ROS), accumulation of TBA-active products and carbonylated proteins but reduced levels of free SH-groups of low molecular weight compounds. It was demonstrated a decrease in the activities of key enzymes of antioxidant system (SOD, catalase, glutathione peroxidase), whereas the activities of pro-oxidant enzymes NAD(P)H-quinone oxidoreductase and semicarbazide-sensitive amine oxidase were shown to be increased. Vitamin D3 (and to greater extent in combination with α-tocopherol) administration (100 IU) on the background of glucocorticoid therapy caused normalizing effects on the level of ROS formation, oxidative modification of biomolecules and activity of antioxidant enzymes resulting in better survival of hepatocytes. These data suggest a potential role of vitamin D3 in the regulation of oxidative metabolism alterations related to hepatotoxic action of glucocorticoids.

In vitro biological assessment of Berberis vulgaris and its active constituent, berberine: antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects.

BACKGROUND: Berberis vulgaris is a well known plant with traditional herbal medical history. The aims of this study was to bioscreen and compare the in vitro biological activity (antioxidant, cholinergic, antidaibetic and the anticancer) of barberry crude extract and berberine active compound. METHODS: The effect of B. vulgaris extract and berberine chloride on cellular thiobarbituric acid reactive species (TBARS) formation, diphenyle-α-picrylhydrazyl (DPPH) oxidation, cellular nitric oxide (NO) radical scavenging capability, superoxide dismutase (SOD), glutathione peroxidase (GPx), acetylcholinesterase (AChE) and α-gulcosidase activities were spectrophotometrically determined. On the other hand, the effect of extract and berberine as anticancer was estimated on three different cell lines which were MCF-7, HepG-2, and Caco-2 cells by using neutral red uptake assay which compared with control normal cells (PBMC). RESULTS: Our results showed that barberry crude extract contains 0.6 mg berberine/mg crude extract. Barberry extract showed potent antioxidative capacity through decreasing TBARS, NO and the oxidation of DPPH that associated with GPx and SOD hyperactivation. Inhibitory effect of berberis crude extract on α-glucosidase was more potent than that of berberine chloride, while both had the same AChE inhibitory effect. Besides, different concentrations of both berberine chloride and barberry ethanolic extract showed to have no growth inhibitory effect on normal blood cells (PBMC). Otherwise, both berberine chloride and barberry ethanolic extract showed to have inhibitory effect on the growth of breast, liver and colon cancer cell lines (MCF7, HepG2 and CACO-2, respectively) at different incubation times starting from 24 hrs up to 72 hrs and the inhibitory effect increased with time in a dose dependent manner. CONCLUSION: This work demonstrates the potential of the barberry crude extract and its active alkaloid, berberine, on suppressing lipid peroxidation, suggesting a promising use in the treatment of hepatic oxidative stress, Alzheimer and idiopathic male factor infertility. Beside, berberis vulgaris ethanolic extract is safe non-toxic extract as it was not inhibit the growth of PBMC that can induce cancer cell death that could return to its powerful antioxidant activity.

Interaction of porcine circovirus type 2 replication with intracellular redox status in vitro.

OBJECTIVES: Redox status influences replication of some viruses but its effect on porcine circovirus type 2 (PCV2), the primary causative agent of the emerging swine disease post-weaning multisystemic wasting syndrome is not known. The interaction of PCV2 replication with intracellular redox status in PK15 cells was examined in this study. METHODS: Intracellular glutathione (GSH) was measured spectrophotometrically by reaction with 5, 5'-dithiobis (2-nitrobenzoic acid). Total superoxide dismutase activity (SOD) was assayed by inhibition of oxyamine oxidation by the xanthine oxidase system. Malondialdehyde (MDA) was assayed spectrophotometrically using the thiobarbituric acid reaction. Both quantification of PCV2 DNA by real-time polymerase chain reaction and indirect immunofluorescence of PCV2-infected cells were used to evaluate the replication of PCV2. RESULTS: Both GSH and SOD decreased significantly at 48 hours after PCV2 infection, whereas MDA concentration increased significantly after 48 hour post-infection. Furthermore, PCV2 replication in PK15 cells was significantly impaired after the elevation of intracellular GSH through treatment with the antioxidant N-acetyl-l-cysteine (NAC), a precursor in GSH synthesis. In contrast, PCV2 replication in PK15 cells was enhanced after reduction of GSH levels through H2O2-mediated oxidation. In addition, NAC treatment blocked the increase of virus replication induced by H2O2. CONCLUSIONS: This study suggests that PCV2 infection induces oxidative stress and that intracellular redox status influences PCV2 replication in PK15 cells.

N-acetylcysteine attenuates subcutaneous administration of bleomycin-induced skin fibrosis and oxidative stress in a mouse model of scleroderma.

BACKGROUND: Several lines of evidence suggest that the generation of reactive oxygen species (ROS) is of major importance in the pathogenesis of scleroderma, and thus antioxidant therapy may be useful for patients with an impaired oxidative defence mechanism. AIM: To examine the effect of N-acetylcysteine (NAC) on skin fibrosis and oxidative stress in a bleomycin (BLM)-induced mouse model of scleroderma. METHODS: We used this mouse model to evaluate the effect of NAC on skin fibrosis and oxidative stress. Skin fibrosis was evaluated by histopathological examination and hydroxyproline content. To measure lipid peroxidation, we used a thiobarbituric acid-reactive species, malondialdehyde (MDA). Oxidative protein damage (carbonyl content) and the activities of catalase (CAT) and superoxide dismutase (SOD) were determined to evaluate oxidative stress in the skin tissue. RESULTS: Treatment with NAC attenuated the skin fibrosis induced by BLM, significantly reducing the MDA and protein carbonyl content in these mice. SOD activity in BLM-only mice and BLM plus NAC-treated mice was increased compared with control mice. However, there was no significant difference in skin SOD activity of mice treated with both BLM and NAC compared with those treated with BLM only. In addition, CAT activity was not altered in the BLM plus NAC mice. CONCLUSIONS: NAC treatment attenuates skin fibrosis in a BLM-induced mouse model of scleroderma, and this is associated with diminished oxidative stress. The results suggest that NAC may be a potential therapeutic agent for patients with scleroderma.

Therapeutic efficacy of melatonin in reducing retinal damage in an experimental model of early type 2 diabetes in rats.

Diabetic retinopathy (DR) is a leading cause of acquired blindness in adults, mostly affected by type 2 diabetes mellitus (T2DM). We have developed an experimental model of early T2DM in adult rats which mimics some features of human T2DM at its initial stages and provokes significant retinal alterations. The aim of this work was to analyze the effect of melatonin on retinal changes induced by the moderate metabolic derangement. For this purpose, adult male Wistar rats received a control diet or 30% sucrose in the drinking water. Three weeks after this treatment, animals were injected with vehicle or streptozotocin (STZ, 25 mg/kg). One day or 3 wk after vehicle or STZ injection, animals were subcutaneously implanted with a pellet of melatonin. Fasting and postprandial glycemia, and glucose, and insulin tolerance tests were analyzed. At 12 wk of treatment, animals which received a sucrose-enriched diet and STZ showed significant differences in metabolic tests, as compared with control groups. Melatonin, which did not affect glucose metabolism in control or diabetic rats, prevented the decrease in the electroretinogram a-wave, b-wave, and oscillatory potential amplitude, and the increase in retinal lipid peroxidation, NOS activity, TNFα, Müller cells glial fibrillary acidic protein, and vascular endothelial growth factor levels. In addition, melatonin prevented the decrease in retinal catalase activity. These results indicate that melatonin protected the retina from the alterations observed in an experimental model of DR associated with type 2 diabetes.

All-trans retinoic acid rescues memory deficits and neuropathological changes in mouse model of streptozotocin-induced dementia of Alzheimer's type.

Recent studies have revealed that aberrant vitamin A signaling may lead to memory deficits in rodents. Present study investigates the potential of all-trans-retinoic acid (ATRA) an agonist at retinoid acid family of receptors, in cognitive dysfunctions associated with experimental dementia. Streptozotocin (STZ) [3 mg/kg, intracerebroventricularly (i.c.v)] was administered on alternate days (day 1 and day 3) to induce dementia in Swiss albino mice. STZ mice were administered ATRA (10 mg/kg; 20 mg/kg, p.o.) for a total of 19 days following second i.c.v injection of STZ [day 4 to day 22]. Morris water maze (MWM) test was performed on days 19, 20, 21, 22 and 23 to assess learning and memory of the animals. Following MWM test, the animals were sacrificed for biochemical and histopathological studies. Extent of oxidative stress was measured by estimating the levels of brain reduced glutathione (GSH) and thiobarbituric acid reactive species (TBARS). Brain acetylcholinestrase (AChE) activity and serum cholesterol levels were also estimated. The brain level of myeloperoxidase (MPO) was measured as a marker of inflammation. STZ produced a marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ treated mice showed marked accentuation of AChE activity, TBARS and MPO levels along with fall in GSH level. Further the stained micrographs of STZ-treated mice indicated pathological changes, severe neutrophilic infiltration and amyloid deposition. ATRA treatment significantly attenuated STZ-induced memory deficits, biochemical and histopathological alterations. The findings demonstrate that the memory restorative ability of ATRA may be attributed to its anti-cholinesterase, anti-oxidative and anti-inflammatory potential.

Differential effects of low-dose fenofibrate treatment in diabetic rats with early onset nephropathy and established nephropathy.

We have previously shown that low-dose fenofibrate treatment has an ability to prevent diabetes-induced nephropathy in rats. We investigated here the comparative pre- and post-treatment effects of low-dose fenofibrate (30 mg/kg/day p.o.) in diabetes-induced onset of nephropathy. Rats were made diabetics by single administration of streptozotocin (STZ, 55 mg/kg i.p.). The development of diabetic nephropathy was assessed biochemically and histologically. Moreover, lipid profile and renal oxidative stress were assessed. Diabetic rats after 8 weeks of STZ-administration developed apparent nephropathy by elevating serum creatinine, blood urea nitrogen and microproteinuria, and inducing glomerular-capsular wall distortion, mesangial expansion and tubular damage and renal oxidative stress. Fenofibrate (30 mg/kg/day p.o., 4 weeks) pretreatment (4 weeks after STZ-administration) markedly prevented diabetes-induced onset of diabetic nephropathy, while the fenofibrate (30 mg/kg/day p.o., 4 weeks) post-treatment (8 weeks after STZ-administration) was less-effective. However, both pre-and post fenofibrate treatments were effective in preventing diabetes-induced renal oxidative stress and lipid alteration in diabetic rats though the pretreatment was slightly more effective. Conversely, both pre-and post fenofibrate treatments did not alter elevated glucose levels in diabetic rats. It may be concluded that diabetes-induced oxidative stress and lipid alteration, in addition to a marked glucose elevation, play a detrimental role in the onset of nephropathy in diabetic rats. The pretreatment with low-dose fenofibrate might be a potential therapeutic approach in preventing the onset of nephropathy in diabetic subjects under the risk of renal disease induction. However, low-dose fenofibrate treatment might not be effective in treating the established nephropathy in diabetic subjects.

Lipid and colour stability of M. longissimus muscle from lambs fed camelina or linseed as oil or seeds.

Colour and lipid stability of M. longissimus dorsi (LD) from sheep fed diets containing different lipid sources (Megalac (MG), camelina oil (CO), linseed oil (LO), NaOH-treated camelina seed (CS), NaOH-treated linseed (LS) or CO treated with ethanolamine (CA)) were examined. After 100 days on-feed, samples of LD were collected, fatty acid profile determined and colour and lipid oxidation (2-thiobarbituric acid reactive substances; TBARS) measured during retail display in high oxygen packaging. The LS ration was most effective in increasing the 18:3n-3 and conjugated linoleic acid (CLA) concentration in muscle. Within camelina, CA resulted in the highest 18:3n-3 and lowest CLA concentration in muscle. There was no difference in colour stability. Oil (seed) supplementation increased TBARS compared to MG in the early part of display while linseed-based rations tended to cause higher TBARS than camelina-based rations. Higher muscle 18:3n-3 concentration was associated with higher oxidation during early retail display but this was not reflected in a loss of colour stability.