Comparison of antioxidant effects of honey, glibenclamide, metformin, and their combinations in the kidneys of streptozotocin-induced diabetic rats

Hyperglycemia-induced increase in oxidative stress is implicated in diabetic complications. This study investigated the effect of metformin and/or glibenclamide in combination with honey on antioxidant enzymes and oxidative stress markers in the kidneys of streptozotocin (60 mg/kg; intraperitoneal)-induced diabetic rats. Diabetic rats were randomized into eight groups of five to seven rats and received distilled water (0.5 mL); honey (1.0 g/kg); metformin (100 mg/kg); metformin (100 mg/kg) and honey (1.0 g/kg); glibenclamide (0.6 mg/kg); glibenclamide (0.6 mg/kg) and honey (1.0 g/kg); metformin (100 mg/kg) and glibenclamide (0.6 mg/kg); or metformin (100 mg/kg), glibenclamide (0.6 mg/kg) and honey (1.0 g/kg) orally once daily for four weeks. Malondialdehyde (MDA) levels, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were significantly elevated while catalase (CAT) activity, total antioxidant status (TAS), reduced glutathione (GSH), and GSH:oxidized glutathione (GSSG) ratio was significantly reduced in the diabetic kidneys. CAT, glutathione reductase (GR), TAS, and GSH remained significantly reduced in the diabetic rats treated with metformin and/or glibenclamide. In contrast, metformin or glibenclamide combined with honey significantly increased CAT, GR, TAS, and GSH. These results suggest that combination of honey with metformin or glibenclamide might offer additional antioxidant effect to these drugs. This might reduce oxidative stress-mediated damage in diabetic kidneys.     

Oral Rg1 supplementation strengthens antioxidant defense system against exercise-induced oxidative stress in rat skeletal muscles

ABSTRACT: BACKGROUND: Previous studies reported divergent results on nutraceutical actions and free radical scavenging capability of ginseng extracts. Variations in ginsenoside profile of ginseng due to different soil and cultivating season may contribute to the inconsistency. To circumvent this drawback, we assessed the effect of major ginsenoside-Rg1 (Rg1) on skeletal muscle antioxidant defense system against exhaustive exercise-induced oxidative stress. METHODS: Forty weight-matched rats were evenly divided into control (N = 20) and Rg1 (N = 20) groups. Rg1 was orally administered at the dose of 0.1 mg/kg bodyweight per day for 10- week. After this long-term Rg1 administration, ten rats from each group performed an exhaustive swimming, and remaining rats considered as non-exercise control. Tibialis anterior (TA) muscles were surgically collected immediately after exercise along with nonexercise rats. RESULTS: Exhaustive exercise significantly (p <0.05) increased the lipid peroxidation of control group, evidenced by elevated malondialdehyde (MDA) levels. The increased oxidative stress after exercise was also confirmed by decreased reduced glutathione to oxidized glutathione ratio (GSH/GSSG ratio) in control rats. However, these changes were completely eliminated in Rg1 group. Catalase (CAT) and glutathione peroxidase (GPx) activities were significantly (p <0.05) increased by Rg1 in non-exercise rats, while no significant change after exercise. Nevertheless, glutathione reductase (GR) and glutathione S-transferase (GST) activities were significantly increased after exercise in Rg1 group. CONCLUSIONS: This study provide compelling evidences that Rg1 supplementation can strengthen antioxidant defense system in skeletal muscle and completely attenuate the membrane lipid peroxidation induced by exhaustive exercise. Our findings suggest that Rg1 can use as a nutraceutical supplement to buffer the exhaustive exercise-induced oxidative stress.     

Anticonvulsant Effects of Topiramate and Lacosamide on Pilocarpine-Induced Status Epilepticus in Rats: A Role of Reactive Oxygen Species and Inflammation

Background: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE. Methods: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus. Results: The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1β levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.     

C60 Fullerene Reduces 3-Nitropropionic Acid-Induced Oxidative Stress Disorders and Mitochondrial Dysfunction in Rats by Modulation of p53, Bcl-2 and Nrf2 Targeted Proteins

C₆₀ fullerene as a potent free radical scavenger and antioxidant could be a beneficial means for neurodegenerative disease prevention or cure. The aim of the study was to define the effects of C₆₀ administration on mitochondrial dysfunction and oxidative stress disorders in a 3-nitropropionic acid (3-NPA)-induced rat model of Huntington’s disease. Animals received 3-NPA (30 mg/kg i.p.) once a day for 3 consecutive days. C₆₀ was applied at a dose of 0.5 mg/kg of body weight, i.p. daily over 5 days before (C₆₀ pre-treatment) and after 3-NPA exposure (C₆₀ post-treatment). Oxidative stress biomarkers, the activity of respiratory chain enzymes, the level of antioxidant defense, and pro- and antiapoptotic markers were analyzed in the brain and skeletal muscle mitochondria. The nuclear and cytosol Nrf2 protein expression, protein level of MnSOD, γ-glutamate-cysteine ligase (γ-GCLC), and glutathione-S-transferase (GSTP) as Nrf2 targets were evaluated. Our results indicated that C₆₀ can prevent 3-NPA-induced mitochondrial dysfunction through the restoring of mitochondrial complexes’ enzyme activity, ROS scavenging, modulating of pro/antioxidant balance and GSH/GSSG ratio, as well as inhibition of mitochondria-dependent apoptosis through the limitation of p53 mitochondrial translocation and increase in Bcl-2 protein expression. C₆₀ improved mitochondrial protection by strengthening the endogenous glutathione system via glutathione biosynthesis by up-regulating Nrf2 nuclear accumulation as well as GCLC and GSTP protein level.     

Antioxidant Protective Effect of Glibenclamide and Metformin in Combination with Honey in Pancreas of Streptozotocin-Induced Diabetic Rats

Hyperglycemia exerts toxic effects on the pancreatic β-cells. This study investigated the hypothesis that the common antidiabetic drugs glibenclamide and metformin, in combination with tualang honey, offer additional protection for the pancreas of streptozotocin (STZ)-induced diabetic rats against oxidative stress and damage. Diabetes was induced in male Sprague Dawley rats by a single dose of STZ (60 mg/kg; ip). Diabetic rats had significantly elevated levels of lipid peroxidation (TBARS), up-regulated activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) while catalase (CAT) activity was significantly reduced. Glibenclamide and metformin produced no significant effects on TBARS and antioxidant enzymes except GPx in diabetic rats. In contrast, the combination of glibenclamide, metformin and honey significantly up-regulated CAT activity and down-regulated GPx activity while TBARS levels were significantly reduced. These findings suggest that tualang honey potentiates the effect of glibenclamide and metformin to protect diabetic rat pancreas against oxidative stress and damage.     

The effects of vitamin E and selenium intake on oxidative stress and plasma lipids in hamsters fed fish oil

The aim of the present work was to test the effects of large-dose supplementation of vitamin E (Vit E) and selenium (Se), either singly or in combination, on fish oil (FO)-induced tissue lipid peroxidation and hyperlipidemia. The supplementation of Se has been shown to lower blood cholesterol and increase tissue concentrations of the antioxidant glutathione (GSH); however, the effects of Se supplementation, either alone or in combination with supplemental Vit E, on FO-induced oxidative stress and hyperlipidemia have not been studied. Male Syrian hamsters received FO-based diets that contained 14.3 wt% fat and 0.46 wt% cholesterol supplemented with Vit E (129 IU d-α-tocopheryl acetate/kg diet) and/or Se (3.4 ppm as sodium selenate) or that contained basal requirements of both nutrients. The cardiac tissue of hamsters fed supplemental Se showed increased concentrations of lipid hydroperoxides (LPO) but decreased oxidized glutathione (GSSG) concentrations. The higher concentrations of LPO in the hearts of Se-supplemented hamsters were not lowered with concurrent Vit E supplementation. In the liver, Se supplementation was associated with higher Se-dependent glutathione peroxidase activity and an increase in the GSH/GSSG ratio, whereas a lower hepatic non-Se-dependent glutathione peroxidase activity was seen with Vit E supplementation. Supplemental intake of Se was associated with lower plasma concentrations of total cholesterol and low density lipoprotein cholesterol plus very low density lipoprotein cholesterol. In view of the pro-oxidative effects of Se supplementation on cardiac tissue, a cautionary approach needs to be taken regarding the plasma lipid-lowering properties of supplemental Se.     

NXP031 Improves Cognitive Impairment in a Chronic Cerebral Hypoperfusion-Induced Vascular Dementia Rat Model through Nrf2 Signaling

Vascular dementia (VaD) is a progressive cognitive impairment caused by a reduced blood supply to the brain. Chronic cerebral hypoperfusion (CCH) is one cause of VaD; it induces oxidative stress, neuroinflammation, and blood-brain barrier (BBB) disruption, damaging several brain regions. Vitamin C plays a vital role in preventing oxidative stress-related diseases induced by reactive oxygen species, but it is easily oxidized and loses its antioxidant activity. To overcome this weakness, we have developed a vitamin C/DNA aptamer complex (NXP031) that increases vitamin C’s antioxidant efficacy. Aptamers are short single-stranded nucleic acid polymers (DNA or RNA) that can interact with their corresponding target with high affinity. We established an animal model of VaD by permanent bilateral common carotid artery occlusion (BCCAO) in 12 week old Wistar rats. Twelve weeks after BCCAO, we injected NXP031 into the rats intraperitoneally for two weeks at moderate (200 mg/4 mg/kg) and high concentrations (200 mg/20 mg/kg). NXP031 administration alleviates cognitive impairment, microglial activity, and oxidative stress after CCH. NXP031 increased the expression of basal lamina (laminin), endothelial cell (RECA-1, PECAM-1), and pericyte (PDGFRβ); these markers maintain the BBB integrity. We found that NXP031 administration activated the Nrf2-ARE pathway and increased the expression of SOD-1 and GSTO1/2. These results suggest that this new aptamer complex, NXP031, could be a therapeutic intervention in CCH-induced VaD.     

Huperzine A Ameliorates Cognitive Deficits in Streptozotocin-Induced Diabetic Rats

The present study was designed to probe the effects of Huperzine A (HupA) on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg) for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT), Acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis.     

Effects of Lacosamide Treatment on Epileptogenesis,Neuronal Damage and Behavioral Comorbidities in a Rat Model of Temporal Lobe Epilepsy

Clinically, temporal lobe epilepsy (TLE) is the most prevalent type of partial epilepsy and often accompanied by various comorbidities. The present study aimed to evaluate the effects of chronic treatment with the antiepileptic drug (AED) lacosamide (LCM) on spontaneous motor seizures (SMS), behavioral comorbidities, oxidative stress, neuroinflammation, and neuronal damage in a model of TLE. Vehicle/LCM treatment (30 mg/kg, p.o.) was administered 3 h after the pilocarpine-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. Our study showed that LCM attenuated the number of SMS and corrected comorbid to epilepsy impaired motor activity, anxiety, memory, and alleviated depressive-like responses measured in the elevated plus maze, object recognition test, radial arm maze test, and sucrose preference test, respectively. This AED suppressed oxidative stress through increased superoxide dismutase activity and glutathione levels, and alleviated catalase activity and lipid peroxidation in the hippocampus. Lacosamide treatment after SE mitigated the increased levels of IL-1β and TNF-α in the hippocampus and exerted strong neuroprotection both in the dorsal and ventral hippocampus, basolateral amygdala, and partially in the piriform cortex. Our results suggest that the antioxidant, anti-inflammatory, and neuroprotective activity of LCM is an important prerequisite for its anticonvulsant and beneficial effects on SE-induced behavioral comorbidities.     

Differential responses to blood pressure and oxidative stress in streptozotocin-induced diabetic wistar-kyoto rats and spontaneously hypertensive rats: effects of antioxidant (honey) treatment

Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress.     

Hepatoprotection by palm tocotrienol‐rich fraction

Tocotrienols, a group of important phytonutrients of palm oil, have been shown to possess antioxidant, anticancer, neuroprotectory, and anti‐inflammatory activities. In this study, our objective was to examine the protective effects of tocotrienol‐rich fraction (TRF) from palm oil on chronic carbon tetrachloride (CCl₄)‐induced hepatotoxicity in rats. Animals were subjected to vehicle only (control), CCl₄ only, CCl₄ + 100 mg/kg silymarin (silymarin), CCl₄ + 25 mg/kg TRF (TRF‐25) and CCl₄ + 50 mg/kg TRF (TRF‐50) treatments for a period of 8 wks. Results showed that daily oral administration of TRF‐25, TRF‐50, and silymarin prevented the elevation of serum glutamate oxalate transaminase (sGOT) and glutamate pyruvate transaminase (sGPT), liver thiobarbituric acid reactive substances (TBARS), triglycerides and total cholesterol levels, as well as enhancing the liver catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels in rats with hepatotoxicity. At 50 mg/kg, the hepatoprotection of TRF was as good as or better than silymarin (100 mg/kg) in normalization of oxidative stress parameters in liver injury rats. These results suggest that TRF exerts effective protection against chronic CCl₄‐induced hepatic injury in rats, and its mechanism of action could be related to reducing oxidative stress in the liver tissue.     

Vitamin D Supplementation: Oxidative Stress Modulation in a Mouse Model of Ovalbumin-Induced Acute Asthmatic Airway Inflammation

Asthma oxidative stress disturbances seem to enable supplementary proinflammatory pathways, thus contributing to disease development and severity. The current study analyzed the impact of two types of oral vitamin D (VD) supplementation regimens on the redox balance using a murine model of acute ovalbumin-induced (OVA-induced) asthmatic inflammation. The experimental prevention group received a long-term daily dose of 50 µg/kg (total dose of 1300 µg/kg), whereas the rescue group underwent a short-term daily dose of 100 µg/kg (total dose of 400 µg/kg). The following oxidative stress parameters were analyzed in serum, bronchoalveolar lavage fluid (BALF) and lung tissue homogenate (LTH): total oxidative status, total antioxidant response, oxidative stress index, malondialdehyde and total thiols. Results showed that VD significantly reduced oxidative forces and increased the antioxidant capacity in the serum and LTH of treated mice. There was no statistically significant difference between the two types of VD supplementation. VD also exhibited an anti-inflammatory effect in all treated mice, reducing nitric oxide formation in serum and the expression of nuclear factor kappa B p65 in the lung. In conclusion, VD supplementation seems to exhibit a protective role in oxidative stress processes related to OVA-induced acute airway inflammation.     

Interaction of silicon-based quantum dots with gibel carp liver: oxidative and structural modifications

Quantum dots (QDs) interaction with living organisms is of central interest due to their various biological and medical applications. One of the most important mechanisms proposed for various silicon nanoparticle-mediated toxicity is oxidative stress. We investigated the basic processes of cellular damage by oxidative stress and tissue injury following QD accumulation in the gibel carp liver after intraperitoneal injection of a single dose of 2 mg/kg body weight Si/SiO₂ QDs after 1, 3, and 7 days from their administration.QDs gradual accumulation was highlighted by fluorescence microscopy, and subsequent histological changes in the hepatic tissue were noted. After 1 and 3 days, QD-treated fish showed an increased number of macrophage clusters and fibrosis, while hepatocyte basophilia and isolated hepatolytic microlesions were observed only after substantial QDs accumulation in the liver parenchyma, at 7 days after IP injection.Induction of oxidative stress in fish liver was revealed by the formation of malondialdehyde and advanced oxidation protein products, as well as a decrease in protein thiol groups and reduced glutathione levels. The liver enzymatic antioxidant defense was modulated to maintain the redox status in response to the changes initiated by Si/SiO₂ QDs. So, catalase and glutathione peroxidase activities were upregulated starting from the first day after injection, while the activity of superoxide dismutase increased only after 7 days. The oxidative damage that still occurred may impair the activity of more sensitive enzymes. A significant inhibition in glucose-6-phosphate dehydrogenase and glutathione-S-transferase activity was noted, while glutathione reductase remained unaltered.Taking into account that the reduced glutathione level had a deep decline and the level of lipid peroxidation products remained highly increased in the time interval we studied, it appears that the liver antioxidant defense of Carassius gibelio does not counteract the oxidative stress induced 7 days after silicon-based QDs exposure in an efficient manner.     

Licochalcone D Ameliorates Oxidative Stress-Induced Senescence via AMPK Activation

Increased oxidative stress is a crucial factor for the progression of cellular senescence and aging. The present study aimed to investigate the effects of licochalcone D (Lico D) on oxidative stress-induced senescence, both in vitro and in vivo, and explore its potential mechanisms. Hydrogen peroxide (200 µM for double time) and D-galactose (D-Gal) (150 mg/kg) were used to induce oxidative stress in human bone marrow-mesenchymal stem cells (hBM-MSCs) and mice, respectively. We performed the SA-β-gal assay and evaluated the senescence markers, activation of AMPK, and autophagy. Lico D potentially reduced oxidative stress-induced senescence by upregulating AMPK-mediated activation of autophagy in hBM-MSCs. D-Gal treatment significantly increased the expression levels of senescence markers, such as p53 and p21, in the heart and hippocampal tissues, while this effect was reversed in the Lico D-treated animals. Furthermore, a significant increase in AMPK activation was observed in both tissues, while the activation of autophagy was only observed in the heart tissue. Interestingly, we found that Lico D significantly reduced the expression levels of the receptors for advanced glycation end products (RAGE) in the hippocampal tissue. Taken together, our findings highlight the antioxidant, anti-senescent, and cardioprotective effects of Lico D and suggest that the activation of AMPK and autophagy ameliorates the oxidative stress-induced senescence.     

Escitalopram Targets Oxidative Stress,Caspase-3, BDNF and MeCP2 in the Hippocampus and Frontal Cortex of a Rat Model of Depression Induced by Chronic Unpredictable Mild Stress

In recent years, escitalopram (ESC) has been suggested to have different mechanisms of action beyond its well known selective serotonin reuptake inhibition. The aim of this study is to investigate the effects of escitalopram on oxidative stress, apoptosis, brain-derived neurotrophic factor (BDNF), Methyl-CpG-binding protein 2 (MeCP2), and oligodendrocytes number in the brain of chronic unpredictable mild stress-induced depressed rats. The animals were randomised in four groups (8 in each group): control, stress, stress + ESC 5 and stress + ESC 5/10. ESC was administered for 42 days in a fixed dose (5 mg/kg b.w.) or in an up-titration regimen (21 days ESC 5 mg/kg b.w. then 21 days ESC 10 mg/kg b.w.). Sucrose preference test (SPT) and elevated plus maze (EPM) were also performed. ESC improved the percentage of sucrose preference, locomotion and anxiety. ESC5/10 reduced the oxidative damage in the hippocampus and improved the antioxidant defence in the hippocampus and frontal lobe. ESC5/10 lowered caspase 3 activity in the hippocampus. Escitalopram had a modulatory effect on BDNF and the number of oligodendrocytes in the hippocampus and frontal lobe and also improved the MeCP2 expressions. The results confirm the multiple pathways implicated in the pathogenesis of depression and suggest that escitalopram exerts an antidepressant effect via different intricate mechanisms.     

Alleviation of Memory Deficit by Bergenin via the Regulation of Reelin and Nrf-2/NF-κB Pathway in Transgenic Mouse Model

The present study aims to determine the neuroprotective effect of Bergenin against spatial memory deficit associated with neurodegeneration. Preliminarily, the protective effect of Bergenin was observed against H₂O₂-induced oxidative stress in HT-22 and PC-12 cells. Further studies were performed in 5xFAD Tg mouse model by administering Bergenin (1, 30 and 60 mg/kg; orally), whereas Bergenin (60 mg/kg) significantly attenuated the memory deficit observed in the Y-maze and Morris water maze (MWM) test. Fourier transform-infrared (FT-IR) spectroscopy displayed restoration of lipids, proteins and their derivatives compared to the 5xFAD Tg mice group. The differential scanning calorimeter (DSC) suggested an absence of amyloid beta (Aβ) aggregation in Bergenin-treated mice. The immunohistochemistry (IHC) analysis suggested the neuroprotective effect of Bergenin by increasing Reelin signaling (Reelin/Dab-1) and attenuated Aβ (1–42) aggregation in hippocampal regions of mouse brains. Furthermore, IHC and western blot results suggested antioxidant (Keap-1/Nrf-2/HO-1), anti-inflammatory (TLR-4/NF-kB) and anti-apoptotic (Bcl-2/Bax/Caspase-3) effect of Bergenin. Moreover, a decrease in Annexin V/PI-stained hippocampal cells suggested its effect against neurodegeneration. The histopathological changes were reversed significantly by Bergenin. In addition, a remarkable increase in antioxidant level with suppression of pro-inflammatory cytokines, oxidative stress and nitric oxide production were observed in specific regions of the mouse brains.     

Effect of Dietary Protein Level and Origin on the Redox Status in the Digestive Tract of Mice

The present study was undertaken to evaluate the effects of high protein (soybean protein or casein) on the balance between production of free radicals and antioxidant level in digestive organs of mice. For this purpose, male (C57BL/6J) mice were adapted to experimental diets containing soybean protein or casein with 20% (normal protein diets, NPDs) or 60% (high protein diets, HPDs), and HPDs supplemented with 0.06g/kg cysteamine. After two weeks of feeding, oxidative and antioxidative parameters in duodenum, liver and pancreas were measured. The results show that ingestion of high protein markedly increased contents of superoxide anion and malondialdehyde (MDA), decreased activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and Na⁺ K⁺-ATPase, and content of reduced glutathione (GSH) in digestive organs of mice (P<0.05). Levels of oxidative parameters were lower and antioxidant capacity of both enzyme and non-enzyme was higher in mice fed with soybean protein than those fed with casein. In groups fed HPDs supplemented with cysteamine, oxidative stress was mitigated. However, oxidative parameter levels were still higher than those of NPD-fed groups. The present study indicates that ingestion of high protein diets could result in an imbalance between oxidant and antioxidant, and thus induce oxidative stress in digestive organs of mice. The oxidative damage was smaller in mice fed with high level of soy protein in comparison with casein.     

Gui-A-Gra Attenuates Testicular Dysfunction in Varicocele-Induced Rats via Oxidative Stress,ER Stress and Mitochondrial Apoptosis Pathway

Gui-A-Gra, a commercial insect powder from Gryllus bimaculatus, is registered as an edible insect by the Korean food and drug administration. The aim of this study was to investigate the effect of Gui-A-Gra on testicular damage induced by experimental left varicocele in male Sprague Dawley rats. A total of 72 rats were randomly divided into the following six groups (12 rats in each group): a normal control group (CTR), a group administrated with Gui-A-Gra 1.63 gm/kg (G1.63), a group administrated with Gui-A-Gra 6.5 gm/kg (G6.5), a varicocele (VC)-induced control group (VC), a VC-induced group administrated with Gui-A-Gra 1.63 gm/kg (VC + G1.63), and a VC-induced group administrated with Gui-A-Gra 6.5 gm/kg (VC + G6.5). Rats were administrated 1.63 or 6.5 gm/kg Gui-A-Gra once daily for 42 days. Indicators of sperm parameters, histopathology, reproductive hormones, oxidative stress, endoplasmic reticulum (ER) stress, inflammation, and mitochondrial apoptosis were analyzed to evaluate effects of Gui-A-Gra on VC-induced testicular dysfunction. Gui-A-Gra administration to VC-induced rats significantly (p < 0.05) increased sperm count and sperm motility, Johnsen score, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, GPx4, and steroidogenic acute regulatory protein (StAR) level. Moreover, pretreatment with Gui-A-Gra significantly (p < 0.05) decreased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positive cells/tubules, serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), testicular tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), reactive oxygen species (ROS)/reactive nitrogen species (RNS) level, glucose-regulated protein-78 (Grp-78), phosphorylated c-Jun-N-terminal kinase (p-JNK), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1α (p-IRE1α), cleaved caspase-3, and BCL2 associated X protein: B-cell lymphoma 2 (Bax: Bcl2) ratio in VC rats. These results suggest that protective effects of Gui-A-Gra on VC-induced testicular injury might be due to its antioxidant, anti-inflammatory, and androgenic activities that might be mediated via crosstalk of oxidative stress, ER stress, and mitochondrial apoptosis pathway.     

The effect of raw soybean on oxidative status of digestive organs in mice

The present study was undertaken to specify the effect of raw soybean on oxidative status of digestive organs in mice. For this purpose, thirty male (C57BL/6J) mice were randomly divided into three groups and fed on different diets as follows: Group 1 was fed on control diet, Group 2 was fed on raw soybean diet and Group 3 was fed on raw soybean diet supplemented with 30 mg/kg cysteamine. After two weeks of feeding, duodenum, liver and pancreas samples were collected to measure oxidative and antioxidative parameters. The results show that ingestion of raw soybean markedly increased contents of superoxide anion and malondialdehyde (MDA) and activity of inducible nitric oxide synthase (iNOS), decreased activity of superoxide dismutase (SOD), T-AOC and content of reduced glutathione (GSH) in digestive organs of mice (P < 0.05). In the group fed with raw soybean diet supplemented with cysteamine, oxidative stress was mitigated. However, oxidative parameter levels were still higher than those of control diet-fed group. The present study indicates that ingestion of raw soybean could result in an imbalance between oxidant and antioxidant, and thus induce oxidative stress in digestive organs of mice.     

Selenoproteome Expression Studied by Non-Radioactive Isotopic Selenium-Labeling in Human Cell Lines

Selenoproteins, in which the selenium atom is present in the rare amino acid selenocysteine, are vital components of cell homeostasis, antioxidant defense, and cell signaling in mammals. The expression of the selenoproteome, composed of 25 selenoprotein genes, is strongly controlled by the selenium status of the body, which is a corollary of selenium availability in the food diet. Here, we present an alternative strategy for the use of the radioactive ⁷⁵Se isotope in order to characterize the selenoproteome regulation based on (i) the selective labeling of the cellular selenocompounds with non-radioactive selenium isotopes (⁷⁶Se, ⁷⁷Se) and (ii) the detection of the isotopic enrichment of the selenoproteins using size-exclusion chromatography followed by inductively coupled plasma mass spectrometry detection. The reliability of our strategy is further confirmed by western blots with distinct selenoprotein-specific antibodies. Using our strategy, we characterized the hierarchy of the selenoproteome regulation in dose–response and kinetic experiments.