Sub-acute administration of metal-organic Framework-5 induces behavioral impairments and augments the levels of oxidative stress and inflammation in the brain of rats.

Metal-organic frameworks (MOFs) are known as potential pharmaceutical carriers because of their structure. Here, we evaluated the sub-acute administrations of MOF-5 on behavioral parameters, oxidative stress, and inflammation levels in rats. Thirty-two male Wistar rats received four injections of saline or MOF-5 at different doses which were 1, 10, and 50 mg/kg via caudal vein. Y-Maze and Morris-Water Maze (MWM) tests were used to explore working memory and spatial learning and memory, respectively. The antioxidant capacity and oxidative stress level of brain samples were assessed by ferric reducing antioxidant power (FRAP) and thiobarbituric acid-reacting substance (TBARS) assay, respectively. The expression levels of GFAP, IL-1ß, and TNF-α were also measured by quantitative real-time reverse-transcription PCR (qRT-PCR). Sub-acute administration of MOF-5 reduced the spatial learning and memory as well as working memory, dose-dependently. The levels of FRAP were significantly reduced in rats treated with MOF-5 at higher doses. The Malondialdehyde (MDA) levels increased at the dose of 50 mg/kg. Additionally, the expression levels of IL-1ß and TNF-α were significantly elevated in the rats' brains that were treated with MOF-5. Our findings indicate that sub-acute administration of MOF-5 induces cognitive impairment dose-dependently which might be partly mediated by increasing oxidative stress and inflammation.

Effect of sub-acute exposure of metal-organic framework-199 on cognitive function and oxidative stress level of brain tissue in rat.

Metal-Organic Framework-199 (MOF-199) is a subgroup of MOFs that is utilized in different medical fields such as drug delivery. In the current study, the effect of sub-acute exposure to MOF-199 on spatial memory, working memory, inflammatory mediators' expression, and oxidative stress level of brain tissue has been investigated. Thirty-two male Wistar rats were randomly divided into four groups as vehicle, MOF-199 at doses 0.3, 3, or 6 mg/kg. After four injections of relevant interventions via tail vein during 14 days, behavioral parameters were investigated using Y-maze and Morris Water Maze (MWM) tests. Oxidative stress was measured by ferric reducing antioxidant power (FRAP) and thiobarbituric acid-reacting substance (TBARS) tests. The expression levels of TNF-α and IL-1ß were assessed by quantitative real-time reverse-transcription PCR (qRT-PCR). No significant differences were observed in working memory, spatial learning and memory of MOF-199 receiving rats. Additionally, the level of oxidative stress and inflammatory genes expression were not remarkably changed in the brain tissues of MOF-199 treated rats. Despite the lack of remarkable toxic effects of sub-acute exposure to MOF-199, more studies with a longer duration of administration are necessary to use this substance for drug delivery systems in diseases related to the nervous system.

Saccharomyces Boulardii alleviates neuroinflammation and oxidative stress in PTZ-kindled seizure rat model.

Previous research have reported that modulating the gut microbiome composition by fecal microbiota transplantation and probiotic administration can alleviate seizure occurrence and severity. Saccharomyces boulardii (SB) is a yeast probiotic that has demonstrated ameliorating effects on anxiety, memory and cognitive deficit, and brain amyloidogenesis. In this research, our goal was to examine the anti-seizure effects of SB on the pentylenetetrazole (PTZ)-kindled male Wistar rats. The animals were randomly categorized into four test groups. The rats were orally administered with saline (control and PTZ groups) or S. boulardii (SB + PTZ and SB groups) for 57 days. From the 29th day of the experiment, the animals received intraperitoneally saline (control and SB groups) or PTZ (PTZ and SB + PTZ groups) on alternate days for 30 days. The administration dose of SB and PTZ was 1010 CFU/ml/day and 35 mg/kg, respectively. We assessed animal seizure behavior, neuroinflammation, oxidative stress, and the levels of matrix metalloproteinase-9 (MMP-9) and brain-derived neurotrophic factor (BDNF) in the hippocampus tissue. S. boulardii hindered the PTZ-induced kindling development. SB treatment elevated glutathione (GSH) and total antioxidant capacity (TAC) and reduced malondialdehyde (MDA) levels. SB also lessened the hippocampal levels of BDNF and MMP-9. Following SB supplementation, proinflammatory cytokines interleukin-1 beta (IL-1ß) and IL-6 were lowered, and anti-inflammatory cytokine IL-10 was enhanced. Overall, our data indicated, for the first time, the positive impact of SB on the PTZ-kindled seizure rat model. The anti-seizure activity of SB was mediated by modulating oxidative stress, neuroinflammation, and MMP-9 and BDNF levels.

The preventive effects of Saccharomyces boulardii against oxidative stress induced by lipopolysaccharide in rat brain.

The brain is sensitive to oxidative stress, which can trigger microglial activation and neuroinflammation. Antioxidant therapies may provide neuroprotection against oxidative stress. In recent years antioxidant effects of probiotics and their possible mechanisms in oxidative stress-related models have been determined. In the current study, for the first time, we assessed the effects of Saccharomyces boulardii on oxidative stress provoked by lipopolysaccharide (LPS) in the rat brain. Four groups of animals were used, including the control, LPS, S. boulardii + LPS, and S. boulardii groups. All animals received either saline or S. boulardii (1010 CFU) by gavage for four weeks. Between days 14 and 22, all animals received either LPS (250 µg/kg) or saline by intraperitoneal (i.p.) injection. S. boulardii was able to inhibit lipid peroxidation and prevent the reduction of antioxidant levels, including glutathione and catalase in the model of oxidative stress induced by LPS in the rat hippocampus and cortex. Also, it increased the lowered ratio of glutathione/oxidized glutathione in both tissues. Serum levels of anti-inflammatory interleukin 10 (IL-10) and proinflammatory cytokines IL-6 and IL-8 increased and decreased, respectively. S. boulardii has potential antioxidant activities in oxidative stress-related model, possibly modulating gut microbiota, immune defense, and antioxidant enzyme activities that can be considered in preventing oxidative stress-related central nervous system (CNS) diseases.

The therapeutic potential of Wild Bitter Melon to ameliorate muscle atrophy in a murine model.

Objective: Muscle atrophy due to immobility is a common complication of many diseases and a consequence of therapeutic processes. Immobility and inactivity have been shown to be associated with increased inflammation. The aim of this study was to investigate the therapeutic potential of Wild Bitter Melon (WBM) (Momordica charantia Linn) on muscle atrophy due to immobility in a mouse model. Materials and Methods: This study was performed in two phases of atrophy and recovery on male BALB/c mice which were divided into 3 groups: control, immobilized, and experimental. The treatment period with WBM at a dose of 400 mg/kg daily by gavage was 17 days, including 7 days of being immobilized and 10 days of recovery. At the end of each phase, half of the mice from each group were examined regarding the four limb grip strength, and then histological and biochemical analyses were done. Results: The tissue level of malondialdehyde (MDA) oxidative stress index in the atrophy phase in the atrophy group (5.4567±0.522) nmol/g compared to the control group (3.455±0.065) nmol significantly (p 0.001) <) increased. Also, the tissue level of MDA in the WBM group (3.87±0.035) showed a significant decrease compared to the atrophy group (p<0.01). The strength percentage of four limbs in the mice of the treatment group (-23.46±2.45) was significantly higher than that of the atrophy group (-30.60±3.15) at the end of the atrophy phase. Conclusion: The results suggest that the use of WBM reduces the degree of inflammation, oxidative stress and muscle damage, as well as muscle atrophy, which may improve the muscle atrophy in mice.

The therapeutic potential of angiotensin-converting enzyme inhibitor enalapril to ameliorate muscle atrophy in a murine model.

Muscle atrophy due to limb immobilization and inactivity is a common consequence of many diseases and treatment processes. One of the systems activated in inflammatory conditions is the renin-angiotensin system (RAS). The present study was conducted with the aim of investigating the effects of one of the angiotensin-converting enzyme (ACE) inhibitors, enalapril, on improving muscle atrophy caused by immobility. The study was conducted in three groups: a control, an atrophy, and an atrophy group treated with enalapril on Balb/c mice. After tying a splint to cause atrophy in one of the legs, daily treatment with enalapril intraperitoneally (dissolved in DMSO) at a dose of 10 mg/kg/day was done for 7 days. On the eighth day, the splint was opened and half of the mice were evaluated. Then, in the recovery phase, treatment with enalapril was continued in the remaining mice for 10 days without a splint. At the end of each phase, the mice were examined for the muscle strength of the lower limb muscles, and histological and biochemical analyses were subsequently carried out. The tissue level of the oxidative stress index MDA was evaluated, which showed a significantly lower level in the enalapril group compared to the atrophy group (*P<0.1). Also, inflammatory factors in the enalapril group showed a decrease compared to the atrophy group. The strength of four limbs in the mice of the treatment group (-18.36 ± 1.70 %) was significantly higher than that of the atrophy group (-30.33 ± 3 %) at the end of the atrophy phase and also after 10 days of recovery. The results suggest that the use of enalapril that reduces the activation of angiotensin II-dependent pro-oxidant and pro-inflammatory pathways may improve the functional disorder and muscle necrosis in the murine model of muscle atrophy.