scholarly journals Repurposing of Dapsone as Neuroprotective Agent on Cuprizone-induced Demyelination via Targeting Nrf2 and NF-kB in C57BL/6 Mice

Author(s):  
Ahmad Reza Dehpour ◽  
Ehsan Khaledi ◽  
Tayebeh Noori ◽  
Ladan Delphi ◽  
Antoni Sureda ◽  
...  

Abstract Multiple Sclerosis (MS) is an inflammatory disorder wherein the myelin of nerve cells in central nervous system is damaged. Fatigue, lack of coordination, blurred vision and mental problems are some of the symptoms of MS. In the current study, we assessed the performance of Dapsone (DAP) on improvement of behavioral dysfunction and preservation of myelin in the cuprizone (CPZ) induced demyelination model via targeting Nrf2 and IKB. MS was induced in C57BL/6 mice through diet supplementation of CPZ (0.2%) for 6 weeks and DAP (12.5 mg/kg/day; i.p.) was administered once daily for the last 2 weeks of treatment. Behavioral tests (pole test and rotarod performance test), LFB and H&E staining and Immunohistochemistry (IHC) staining of p-Nrf2 and p-IKB were performed to evaluate locomotor coordination, observe the area of demyelination in corpus callosum respectively. Furthermore, superoxide dismutase (SOD), and nitrite were measured. Based on the results of the weight of mice, it was shown that the weight of the groups receiving CPZ decreased compared to the control group (P < 0.001), while administration of dapsone increased the weight (P < 0.001). Pole test showed that CPZ increased latency time to fall (P <0.01) but the latency to reach the floor in DAP-CPZ group was significantly shorter than the CPZ group (P <0.001). Rotarod performance test showed the effect of CPZ in reducing fall time in CPZ group (P <0.01) however treatment with DAP significantly increased fall time (P < 0.001). In LFB staining increased demyelination was seen in the CPZ group and decreased demyelination was observed in the DAP group. IHC staining results of p-Nrf2 and p-IKB showed that CPZ significantly decreased p-Nrf2 and elevated p-IKB levels compared with the control group (P <0.001), but in DAP -treated groups markedly modified these changes (P < 0.001). CPZ feeding led to increase of brain nitrite levels and reduced SOD activity (P <0.05) but in DAP-treated considerably reversed CPZ-induced changes in nitrite and SOD activity level (P <0.001). These data support the suggestion that the beneficial properties of dapsone on the CPZ-induced demyelination are mediated by targeting Nrf2 and NF-kB pathways.

2012 ◽  
Vol 63 (3) ◽  
pp. 247-254 ◽  
Author(s):  
Aleksandra Buha ◽  
Zorica Bulat ◽  
Danijela Đukić-Ćosić ◽  
Vesna Matović

Cadmium (Cd) has been recognised as one of the most important environmental and industrial pollutants, and up-to-date investigations have shown that one of the mechanisms of its toxicity is associated with the induction of oxidative stress. The aim of this study was to determine the connection between acute oral and intraperitoneal exposure to Cd and parameters indicative of oxidative stress in the plasma of rats, as well as to examine the potential protective effect of magnesium (Mg) in conditions of acute oral and intraperitoneal Cd poisoning. The experiment was performed on male albino Wistar rats (n=40) randomly divided into control group, Cdor group that received 30 mg kg-1 b.w. Cd by oral gavage, Cd+Mgor group that orally received 50 mg kg-1 b.w. Mg one hour before oral Cd, Cdip group that received 1.5 mg kg-1 b.w. Cd intraperitoneally, and Cd+Mgip group that intraperitoneally received 3 mg kg-1 b.w. Mg 10 min before intraperitoneal Cd. The animals were sacrifi ced 24 h after treatment and the following parameters were measured: superoxidedismutase activity, superoxide anion, total oxidative status, advanced oxidation protein products, and malondialdehyde. All parameters of oxidative stress in rat plasma were negatively affected by Cd treatment with more pronounced negative effects after intraperitoneal treatment, with the exception of superoxide dismutase (SOD) activity. Although both oral and intraperitoneal Mg pretreatment had protective effects, more pronounced benefi cial effects were observed after oral administration, since it managed to completely prevent Cd-induced changes in the investigated parameters. The observed results support the use of Mg as potential protective agent against toxic effects caused by Cd.


2016 ◽  
Vol 86 (1-2) ◽  
pp. 27-35 ◽  
Author(s):  
Burcu Gul Baykalir ◽  
Dilek Aksit ◽  
Mustafa Selim Dogru ◽  
Arzu Hanım Yay ◽  
Hasan Aksit ◽  
...  

Abstract. Inflammatory bowel disease (IBD) is an inflammatory disorder involving colitis. Lycopene is a naturally occurring carotenoid that has attracted considerable attention as a potential chemopreventive agent. The impact of lycopene on colitis is currently unknown. The aim of this study was to investigate the protective effects of lycopene in a rat model of colitis induced by acetic acid. The animals were randomly divided into the following five groups: the control group, colitis group, colitis + sulfasalazine group as a positive control group, colitis + lycopene and lycopene groups. Colonic mucosal injury was assessed by biochemical and histopathological examinations. Malondialdehyde (MDA), superoxide dismutase (SOD) activity, total antioxidant status (TAS), ceruloplasmin (CPN), total sialic acid and iron (Fe) levels were evaluated in blood samples. MDA, SOD, TAS and DNA fragmentation levels were also measured in colon tissues. MDA (p < 0.05), total sialic acid (p < 0.05) and DNA fragmentation levels (p < 0.01) were significantly higher, and the activity of the antioxidant enzyme were lower in the colitis group than in the control group. Treatments with lycopene in the colitis decreased MDA, total sialic acid and DNA fragmentation levels, while SOD activity (p < 0.05), TAS (in colon p < 0.05; in serum p < 0.01), CPN (p < 0.05) and Fe levels (p < 0.05) were significantly increased. The histopathological evaluation also confirmed the foregoing findings. Treatment with lycopene ameliorated the biochemical and pathological alterations caused by colitis. The results obtained in this study indicate that lycopene may exert protective effects in experimental colitis and might, therefore, be useful for treatment of IBD.


2016 ◽  
Vol 32 (4) ◽  
pp. 291-297 ◽  
Author(s):  
Dubi Lufi ◽  
Shachar Pan

Abstract. Several studies have shown that Continuous Performance Tests (CPT) can diagnose Attention Deficit Hyperactivity Disorder (ADHD) better than other tests. Research reporting comparisons of two or more CPT-type tests is scarce. The purpose of the study was to compare the Mathematics Continuous Performance Test (MATH-CPT) with another CPT-type test (CPT II) and a questionnaire (the Brown Scale). The comparison was carried out by looking at correlations among subscales and checking the precision of detecting ADHD. Ninety-five high school and college students participated in the study, 41 with ADHD were the research group and 54 were the control group. The participants performed the two tests and answered the questionnaire. The results showed that the MATH-CPT correctly identified 74.50% of the participants of both groups as compared to the 71.60% of the CPT II. Correlations between the two CPT-type tests were moderate; however, they were similar to correlations found in other studies comparing similar tools. The MATH-CPT, final attention formula, showed significant correlations with the Brown scales, while the CPT II, confidence index associated with ADHD assessment, showed nonsignificant correlations with the questionnaire. The study indicated that MATH-CPT can be used with a clinical population of ADHD and for research purposes.


Author(s):  
Oleg Melnikov ◽  
Diana Zabolotnaya ◽  
Alexander Bredun ◽  
Bogdan Bil ◽  
Oksana Rylska ◽  
...  

Introduction: In recently ears factors of innate immunity both cellular and humoral have been paid considerable attention as they are a protective barrier of a fast response and that is why they are largely concentrated at the intersection of the digestive tract and airways. The data concerning the activity level of factors of innate immunity in the upper airways affected by nonspecific inflammatory processes is insufficient and sparse and therefore the purpose of this research was to study the content of humoral factors of innate immunity in the oropharyngeal secretion (ORS) of patients with chronic infectious inflammatory diseases of the upper airways in remission. Materials and Methods: There was an examination of 16 patients with chronic rhinosinusitis (CRS) of bacterial genesis (15-40 years old), 12 patients with rhinopharyngitis of post-viral genesis (8-16 years old), 12 people with scleroma from 30 tо 52 years of age (atrophic form), 10 patients with chronic tonsillitis in remission (from 10 to 33 years of age) and 11 patients of a control group (practically healthy donors from 12 tо 40 years of age). The content of MIP-1b, defensin-1β, lactoferrin, lysozyme, α-interferon was studied in the nonstimulated OPS. Statistics were carried out using Mann-Whitney U-test. Results: The greatest number of deviations in the decrease in the content of the examined nonspecific protective factors was found in cases of scleroma, chronic tonsillitis and chronic rhinosinusitis (p<0,05). The lack of protective humoral factors of innate immunity can be evidence of local immunodeficiency even in remission, which is a pathophysiological component of the maintenance of chronic inflammation. Conclusion: The decrease int he quantitative composition of factors of innate immunity in the oropharyngeal secretion of patients with chronic infectious inflammatory diseases of the airways is an objective ground not only for a replacement therapy, but also for the use of immune response modifiers from photo-immune modulators to “genuine immune modulators” controlling the state of the factors of both innate immunity and immunoglobulins, primarily of secretory type, the level and functionality of various groups of immunocompetent and accessory cells.


2021 ◽  
pp. 036354652110130
Author(s):  
Stefano Nuccio ◽  
Luciana Labanca ◽  
Jacopo Emanuele Rocchi ◽  
Pier Paolo Mariani ◽  
Paola Sbriccoli ◽  
...  

Background: The acute effects of exercise on anterior knee laxity (AKL) and anterior knee stiffness (AKS) have been documented in healthy participants, but only limited evidence has been provided for athletes cleared to return to sports after anterior cruciate ligament (ACL) reconstruction (ACLR). Purpose/Hypothesis: The purpose was to determine if 45 minutes of a soccer match simulation lead to acute changes in AKL and AKS in soccer players returning to sport within 12 months after ACLR. We hypothesized that the reconstructed knee of the ACLR group would exhibit an altered response to sport-specific exercise. Study Design: Controlled laboratory study. Methods: A total of 13 soccer players cleared to return to sport after ACLR and 13 healthy control soccer players matched for age, physical activity level, limb dominance, and anthropometric characteristics were recruited. To assess the effects of a standardized soccer match simulation (Soccer Aerobic Field Test [SAFT45]) on AKL and AKS, an arthrometric evaluation was carried out bilaterally before and immediately after SAFT45. To conduct a comprehensive examination of the force-displacement curve, the absolute and side-to-side difference (SSD) values of both AKL and AKS were extracted at 67, 134, and 200 N. Results: The ACLR and control groups showed similar AKL and AKS at baseline ( P > .05). In response to SAFT45, laxity increased bilaterally at all force levels by 14% to 17% only in the control group ( P < .025). Similarly, AKS at 134 and 200 N decreased in response to SAFT45 only in the control group (10.5% and 20.5%, respectively; P < .025). After SAFT45, the ACLR group had 1.9 and 2.5 times higher SSDs of AKS at 67 and 134 N compared with the control group, respectively ( P < .025), as well as a 1.9 times higher SSD of AKS at 134 N compared with baseline ( P = .014). Conclusion: Soccer players at the time of return to sport after ACLR showed an altered mechanical response to a sport-specific match simulation consisting of bilaterally unchanged AKL and AKS. Clinical Relevance: Soccer players showing altered AKL and AKS in response to exercise after ACLR may not be ready to sustain their preinjury levels of sport, thus potentially increasing the risk of second ACL injuries.


Forests ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 19
Author(s):  
Xiaodeng Shi ◽  
Siyu Chen ◽  
Zhongkui Jia

The effects of varieties, concentrations, and number of applications of plant growth retardants (PGRs) on the morphological, physiological, and endogenous hormones of Magnolia wufengensis L.Y. Ma et L. R. Wang were assessed to obtain the most suitable dwarfing protocol for M. wufengensis and to provide theoretical support and technical guidance for the cultivation and promotion of this species. One-year-old M. wufengensis ‘Jiaohong No. 2’ grafted seedlings served as the experimental materials. In the first part of the experiment, three PGRs (uniconazole, paclobutrazol, prohexadione calcium), three concentrations (500, 1000, 1500 ppm), and three applications (one, three, and five applications) were applied in dwarfing experiments to perform L9 (34) orthogonal tests. In the second part of the study, dwarfing experiments were supplemented with different high uniconazole concentrations (0, 1500, 2000, 2500 ppm). Spraying 1500 ppm uniconazole five times achieved the best M. wufengensis dwarfing effect, related indicators of M. wufengensis under this treatment were better than other treatment combinations. Here, M. wufengensis plant height, internode length, scion diameter, and node number were significantly reduced by 56.9%, 62.6%, 72.8%, and 74.4%, respectively, compared with the control group. This treatment increased superoxide dismutase (SOD) activity by 66.0%, peroxidase (POD) activity by 85.0%, soluble protein contents by 43.3%, and soluble sugar contents by 27.6%, and reduced malondialdehyde (MDA) contents by 32.1% in leaves of M. wufengensis compared with the control. The stress resistance of M. wufengensis was enhanced. The treatment also reduced gibberellin (GA3) levels by 73.0%, auxin (IAA) by 58.0%, and zeatin (ZT) by 70.6%, and increased (abscisic acid) ABA by 98.1% in the leaves of M. wufengensis. The uniconazole supplementation experiment also showed that 1500 ppm was the optimal uniconazole concentration. The leaves exhibited abnormalities such as crinkling or adhesion when 2000 or 2500 ppm was applied. Given the importance of morphological indicators and dwarfing for the ornamental value of M. wufengensis, the optimal dwarfing treatment for M. wufengensis was spraying 1500 ppm uniconazole five times.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Jun Ma ◽  
Xiankun Zeng ◽  
Min Zhou ◽  
Le Cheng ◽  
Difeng Ren

AbstractSpirulina platensis protein hydrolysates were prepared by digesting protein extracts with papain, and the hydrolysates were separated into 30, 10, and 3 kDa weights using membrane ultrafiltration. The 0–3 kDa low-molecular-weight Spirulina peptides (LMWSPs) proved the highest chemical antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability, hydroxyl radical (·OH) scavenging activities and total antioxidant capacity. Cellular antioxidant ability of LMWPs fractions against 2000 μg/mL H2O2 induced oxidative damage of L02 cells were investigated. The MTT assay results displayed that LMWSPs at different concentrations (0–1000 μg/mL) had proliferation effect on the L02 cells and that treatment of the L02 cells with the 1000 μg/mL LMWSPs (0–3 kDa) significantly prevented H2O2-induced oxidative damage compared with control cells. Moreover, the 2′,7′-dichlorofluorescein diacetate (DCFH-DA) fluorescent probe assay showed that the levels of ROS and NO were significantly lower in the experimental group that was treated with the peptides for 24 h than in the control group. Furthermore, using the corresponding kits, the treatment inhibited the reduction of SOD activity and the increase of MDA contents in the L02 cells. Therefore, LMWSPs (0–3 kDa) may have potential applications in antioxidant and liver health products.


Author(s):  
Lee Wei Yang ◽  
Santosh Fattepur ◽  
Kiran Chanabasappa Nilugal ◽  
Fadli Asmani ◽  
Eddy Yusuf ◽  
...  

Objective: The present study was designed to determine the neuroprotective effect of Abelmoschus esculentus L. on alloxan-induced diabetic neuropathy in rats.Methods: Diabetes was induced in rats with a single intraperitoneal injection of alloxan monohydrate (130 mg/kg b.w). The ethanol extract of A. esculentus L. at a dose of 100 and 200 mg/kg of body weight was administered at single dose per day to alloxan-induced diabetic rats for 21 days. The fasting blood glucose was screened in the intermittent on day 0, day 14, and day 21. Behavioral tests such as thermal hyperalgesia test and rotarod performance test were performed to assess the thermal sensitivity and muscle grip strength. At the end of the study period, experimental animals were sacrificed and sciatic nerve tissues were obtained for histopathological investigation.Results: Animals treated with A. esculentus L. extarct at a dose of 200 mg/kg of body weight significantly reduced (p<0.05) in hyperglycemia and thermal hyperalgesia and significantly increased (p<0.05) in rotarod performance. The sciatic nerve fiber of diabetic rats receiving 200 mg/kg of body weight of A. esculentus L. extract also shows no swelling of nerve fibers, and lesser demyelination was observed.Conclusion: These findings demonstrate that A. esculentus L. exhibits significant antidiabetic and neuroprotective effect against alloxan-induced diabetic neuropathy in rats.


Cephalalgia ◽  
1994 ◽  
Vol 14 (3) ◽  
pp. 215-218 ◽  
Author(s):  
T Shimomura ◽  
H Kowa ◽  
T Nakano ◽  
A Kitano ◽  
H Marukawa ◽  
...  

Superoxide dismutase (SOD) is a radical-scavenging enzyme. We determined Cu, Zn-SOD concentrations and activities in platelets from subjects with migraine and tension-type headaches. Thirty migraine without aura (MWoA) patients, 9 migraine with aura (MWA) patients, and 53 tension-type headache patients were selected for study. Thirty healthy volunteers composed the control group. Concentrations of platelet SOD were determined using enzyme-linked immunosorbent assay techniques. The activity of platelet SOD was determined by measuring reductivity of nitroblue tetrazolium. Low concentrations of platelet SOD were found in patients with MWA and MWoA. Platelet SOD activity decreased in MWA patients but not in patients with MWoA or tension-type headaches. These findings suggest vulnerability to oxidative stress in patients with migraine. It is suggested that low platelet SOD levels may play an important role in the etiology of migraine.


2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Suchittra Samuhasaneeto ◽  
Duangporn Thong-Ngam ◽  
Onanong Kulaputana ◽  
Doungsamon Suyasunanont ◽  
Naruemon Klaikeaw

To study the mechanism of curcumin-attenuated inflammation and liver pathology in early stage of alcoholic liver disease, female Sprague-Dawley rats were divided into four groups and treated with ethanol or curcumin via an intragastric tube for 4 weeks. A control group treated with distilled water, and an ethanol group was treated with ethanol (7.5 g/kg bw). Treatment groups were fed with ethanol supplemented with curcumin (400 or 1 200 mg/kg bw). The liver histopathology in ethanol group revealed mild-to-moderate steatosis and mild necroinflammation. Hepatic MDA, hepatocyte apoptosis, and NF-κB activation increased significantly in ethanol-treated group when compared with control. Curcumin treatments resulted in improving of liver pathology, decreasing the elevation of hepatic MDA, and inhibition of NF-κB activation. The 400 mg/kg bw of curcumin treatment revealed only a trend of decreased hepatocyte apoptosis. However, the results of SOD activity, PPARγprotein expression showed no difference among the groups. In conclusion, curcumin improved liver histopathology in early stage of ethanol-induced liver injury by reduction of oxidative stress and inhibition of NF-κB activation.


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