scholarly journals Effect of cogon grass root ethanol extract on fatty acid binding protein 4 and oxidative stress markers in a sepsis mouse model

F1000Research ◽  
2022 ◽  
Vol 10 ◽  
pp. 1161
Author(s):  
Mirasari Putri ◽  
Bening Mauliddina Rastiarsa ◽  
Raden Aliya T. M. Djajanagara ◽  
Ghaliby Ardhia Ramli ◽  
Neni Anggraeni ◽  
...  

Background: Sepsis causes several immunological and metabolic alterations that induce oxidative stress. The modulation of fatty acid-binding protein 4 (FABP4) has been shown to worsen this condition. Extract of cogon grass root (ECGR) contains flavonoids and isoeugenol compounds that exhibit anti-inflammatory and antioxidant properties. This study aimed to assess the effects of ECGR on FABP4 and oxidative stress–related factors in a sepsis mouse model. Methods: Twenty-nine male mice (Mus musculus) of the Deutsche Denken Yoken strain were divided into four groups: group 1, control; group 2, mice treated with 10 μL/kg body weight (BW) lipopolysaccharide (LPS); and groups 3 and 4, mice pre-treated with 90 and 115 mg/kg BW, respectively, and then treated with 10 μL/kg BW LPS for 14 d. Blood, liver, lymph, and cardiac tissue samples were collected and subjected to histological and complete blood examinations. Antioxidant (Glutathione peroxidase 3 (GPx3) and superoxide dismutase), FABP4 levels, and immune system-associated biomarker levels (TNF-α, IL-6 and IL-1β ) were measured. Results: Significant increases in platelet levels (p = 0.03), cardiomyocyte counts (p =0.004), and hepatocyte counts (p = 0.0004) were observed in group 4 compared with those in group 2. Conversely, compared with those in group 2, there were significant decreases in TNF-α expression in group 3 (p = 0.004), white pulp length and width in group 4 (p = 0.001), FABP4 levels in groups 3 and 4 (p = 0.015 and p = 0.012, respectively), lymphocyte counts in group 4 (p = 0.009), and monocyte counts (p = 0.000) and polymorphonuclear cell counts in the livers (p = 0.000) and hearts (p = 0.000) of groups 3 and 4. GPx3 activity was significantly higher in group 3 than in group 1 (p = 0.04). Conclusions: ECGR reduces FABP4 level and modulating oxidative stress markers in sepsis mouse model.

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1161
Author(s):  
Mirasari Putri ◽  
Bening Mauliddina Rastiarsa ◽  
Raden Aliya T. M. Djajanagara ◽  
Ghaliby Ardhia Ramli ◽  
Neni Anggraeni ◽  
...  

Background: Sepsis causes several immunological and metabolic alterations that induce oxidative stress. The modulation of fatty acid-binding protein 4 (FABP4) has been shown to worsen this condition. Extract of cogon grass root (ECGR) contains flavonoids and isoeugenol compounds that exhibit anti-inflammatory and antioxidant properties. This study aimed to assess the effects of ECGR on FABP4 and oxidative stress–related factors in a sepsis mouse model. Methods: Twenty-nine male mice (Mus musculus) of the Deutsche Denken Yoken strain were divided into four groups: group 1, control; group 2, mice treated with 10 μL/kg body weight (BW) lipopolysaccharide (LPS); and groups 3 and 4, mice pre-treated with 90 and 115 mg/kg BW, respectively, and then treated with 10 μL/kg BW LPS for 14 d. Blood, liver, spleen, and cardiac tissue samples were collected and subjected to histological and complete blood examinations. Antioxidant activity, FABP4 levels, and immune system-associated biomarker levels were also measured. Results: Significant increases in platelet levels (p = 0.03), cardiomyocyte counts (p =0.004), and hepatocyte counts (p = 0.0004) were observed in group 4 compared with those in group 2. Conversely, compared with those in group 2, there were significant decreases in TNF-α expression in group 3 (p = 0.004), white pulp length and width in group 4 (p = 0.001), FABP4 levels in groups 3 and 4 (p = 0.015 and p = 0.012, respectively), lymphocyte counts in group 4 (p = 0.009), monocyte counts (p = 0.000) and polymorphonuclear cell counts in the livers (p = 0.000) and hearts (p = 0.000) of groups 3 and 4. Gpx3 activity was significantly higher in group 3 than in group 1 (p = 0.04). Conclusions: Cogon grass root may aid in the development of herbal medicines and specific treatments for sepsis.


Author(s):  
Neveen A. Salem ◽  
Amani M. Alsaedi ◽  
Bedor G. Alasmari ◽  
Razan Z. Almarghalani ◽  
Shahad M. Algobe ◽  
...  

Pregabalin (Lyrica) is an analog of the gamma-aminobutyric acid neurotransmitter,   approved for the treatment of epilepsy, generalized anxiety disorder, neuropathic pain, and fibromyalgia. The possibility for abuse and/or dependence on pregabalin has risen recently. Pregabalin is controlled in many countries including Saudi Arabia. However, unofficial use of this substance is also on the increase. The purpose of this study is to assess the potential neurotoxic effects associated with overdose prolonged pregabalin supplementation. Forty male Wistar rats were divided into Group (1) normal control received distilled water, Group (2) received pregabalin (150mg/kg), Group (3) received pregabalin (300 mg/kg), and Group (4) received pregabalin (600 mg/kg). pregabalin consumption in different doses resulted in significant dysregulation in neurotransmitter release, upsurge oxidative stress markers via enhancing lipid peroxidation and depleting antioxidant markers. Also, pregabalin doses evoked brain tissue inflammation through elevating TNF-α, IL-1β, and MCP-1, Moreover promoted brain tissue apoptosis by activating caspase -3 and suppressed Bcl2. Pregabalin effects on the aforementioned parameters were dose-dependent. These findings could highlight the potential neurotoxic effect of prolonged abuse of pregabalin supplementation through dysregulating brain neurochemical, inflammatory, oxidant/antioxidant, and apoptotic mediators.


2020 ◽  
Vol 70 (1) ◽  
pp. 121-127
Author(s):  
David Calderón Guzmán ◽  
Norma Osnaya Brizuela ◽  
Maribel Ortíz Herrera ◽  
Armando Valenzuela Peraza ◽  
Gerardo Barragán Mejía ◽  
...  

AbstractThe aim of the present study was to determine the effect of sildenafil on dopamine, 5-hydroxyindol acetic acid (5-HIAA) and selected biomarkers of oxidative stress in the brain of hypoglycemic rats. The animals were treated intraperitoneally as follows: group 1 (control), saline solution; group 2, insulin (10 U per rat or 50 U kg−1); group 3, insulin + single dose of sildenafil (50 U kg−1 + 50 mg kg–1); group 4, insulin + three doses of sildenafil every 24 hours (50 U kg−1 + 50 mg kg−1). In groups 2, 3 and 4, insulin was administered every 24 hours for 10 days. Blood glucose was measured after the last treatment. On the last day of the treatment, the animals´ brains were extracted to measure the levels of oxidative stress markers [H2O2, Ca2+,Mg2+-ATPase, glutathione and lipid peroxidation (TBARS)], dopamine and 5-HIAA in the cortex, striatum and cerebellum/medulla oblongata by validated methods. The results suggest that administration of insulin in combination with sildenafil induces hypoglycemia and hypotension, enhances oxidative damage and provokes changes in the brain metabolism of biogenic amines. Administration of insulin and sildenafil promotes biometabolic responses in glucose control, namely, it induces hypoglycemia and hypotension. It also enhances oxidative damage and provokes changes in the brain metabolism of biogenic amines.


2018 ◽  
Vol 46 (1) ◽  
Author(s):  
Ricardo Christ ◽  
Aleksandro Schafer Da Silva ◽  
Mateus Eloir Grabriel ◽  
Luan Cleber Henker ◽  
Renan Augusto Cechin ◽  
...  

  Background: Nitrate and nitrite poisoning is associated with pasture intake that has high nitrate levels and leads to acute methemoglobinemia. Pasture may accumulate nitrate under certain conditions, such as excessively fertilized soil or en­vironmental conditions that enhance the N absorption (rain preceded by a period of drought). After ingestion of plants, this substrate reaches the rumen and, in physiological conditions, is reduced to nitrite and afterward to ammonia. The aim of this study was to evaluate changes in cholinesterase activities and oxidative stress caused by subclinical poisoning for nitrate and nitrite in cattle fed with Pennisetum glaucum in three different fertilization schemes. Materials, Methods & Results: In order to perform the experimental poisoning, the pasture was cultivated in three dif­ferent paddocks: with nitrogen topdressing (urea; group 1), organic fertilizer (group 2) or without fertilizer (group 3; control). Nitrate accumulation in forage was evaluated by the diphenylamine test. After food fasting of 12 h, nine bovine were randomly allocated to one of the experimental groups and fed with fresh forage (ad libitum) from respective pad­dock. In different time points from beginning of pasture intake (0, 2, 4, 6 and 9 h) heart rate and respiratory frequency were assessed, as well as mucous membrane color and behavioral changes. Blood samples from jugular vein into vials with and without anticoagulant were collected. From blood samples, serum nitrite levels, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme activity were evaluated, as well as oxidative stress through the following param­eters: levels of nitrate/nitrite (NOx), thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS), beyond the antioxidant system by enzyme activity measurement of catalase (CAT) and superoxide dismutase (SOD). The diphenylamine test was positive to group 1 and 2, so that the pasture presented 3.16 mg/kg, 2.98 mg/kg and 1.67 mg/kg of nitrate for group 1, 2 and 3, respectively. In addition, cows from group 1 demonstrated increased (P < 0.05) nitrite levels in serum, compared to other groups, and greater heart rate after 9 h (P < 0.05). The AChE and BChE activity in group 1 showed significant increase (P < 0.05) at 4 and 6 h (AChE), and 4 and 9 h (BChE) compared to group 3. Also, NOx levels were lower at 6 and 9 h (P < 0.05) and at 9 h (P < 0.05) for animals of group 1 and 2, respectively, when compared to group 3. Furthermore, in the group 1 levels of ROS and TBARS were significantly higher (P < 0.05) after 2 and 4 h, and 6 and 9 h compared to other groups, respectively. The CAT activity increased significantly (P < 0.05) with 2 and 4 h of the experiment, but on the other hand, decreased at 6 and 9 h in group 1. Nevertheless, the animals from group 2 presented only a significant reduction in this enzyme activity at 9 h. Furthermore, SOD activity was reduced in animals of groups 1 (P < 0.05) at 4, 6 and 9 h, compared to other groups. Discussion: It was concluded that the nitrate and nitrite poisoning by pasture intake cultivated and fertilized with urea leads to increased levels of serum nitrite, as well as the cholinesterase activity and causes oxidative stress in cattle. It is conjectured that the cholinesterase activity and oxidative stress may assist in understanding the pathophysiology of changes caused by poisoning.Keywords: plant toxicology, poisoning, methemoglobin, cholinergic system, oxidative stress.


2020 ◽  
Vol 29 ◽  
pp. 096368972095414
Author(s):  
Kun-Chen Lin ◽  
Jun-Ning Yeh ◽  
Yi-Ling Chen ◽  
John Y. Chiang ◽  
Pei-Hsun Sung ◽  
...  

This study tested the hypothesis that both allogenic adipose-derived mesenchymal stem cells (ADMSCs) and human inducible pluripotent stem cell-derived MSCs (iPS-MSCs) offered a comparable effect for protecting the lung against ischemia-reperfusion (IR) injury in rodent through downregulating the inflammatory, oxidative stress, and autophagic signaling pathways. Adult male Sprague–Dawley rats ( n = 32) were categorized into group 1 (sham-operated control), group 2 (IRI), group 3 [IRI + ADMSCs (1.0 × 106 cells)/tail-vein administration at 0.5/18/36 h after IR], and group 4 [IRI + iPS-MSCs (1.0 × 106 cells)/tail-vein administration at 0.5/18/36 h after IR], and lungs were harvested at 72 h after IR procedure. In vitro study demonstrated that protein expressions of three signaling pathways in inflammation (TLR4/MyD88/TAK1/IKK/I-κB/NF-κB/Cox-2/TNF-α/IL-1ß), mitochondrial damage/cell apoptosis (cytochrome C/cyclophilin D/DRP1/ASK1/APAF-1/mitochondrial-Bax/caspase3/8/9), and autophagy/cell death (ULK1/beclin-1/Atg5,7,12, ratio of LCB3-II/LC3B-I, p-AKT/m-TOR) were significantly higher in lung epithelial cells + 6h hypoxia as compared with the control, and those were significantly reversed by iPS-MSC treatment (all P < 0.001). Flow cytometric analysis revealed that percentages of the inflammatory cells in bronchioalveolar lavage fluid and circulation, and immune cells in circulation/spleen as well as circulatory early and late apoptotic cells were highest in group 2, lowest in group 1, and significantly higher in group 3 than in group 4 (all P < 0.0001). Microscopy showed the lung injury score and numbers of inflammatory cells and Western blot analysis showed the signaling pathways of inflammation, mitochondrial damage/cell apoptosis, autophagy, and oxidative stress exhibited an identical pattern of flow cytometric results among the four groups (all P < 0.0001). Both xenogeneic and allogenic MSCs protected the lung against IRI via suppressing the inflammatory, oxidative stress, and autophagic signaling.


2019 ◽  
Vol 08 (02) ◽  
pp. 113-118
Author(s):  
Hakan AK ◽  
Iskender Samet Daltaban ◽  
Sevilay Vural

Abstract Aim In this experimental study, we aimed to investigate possible healing effects of memantine hydrochloride, an N-methyl-d-aspartate (NMDA) antagonist, with clinical, biochemical, and histopathologic methods on acute peripheral nerve injury (PNI). Material and Method Forty-eight adult Wistar albino rats were divided into four groups (n = 12). The groups were arranged as sham-operated group (group 1), acute compression model group (group 2), trauma + low-dose memantine group (group 3), and trauma + high-dose memantine group (group 4). Memantine was administered intraperitoneally for 7 days. Subjects were sacrificed after the measurement of the sciatic nerve function index (SNFI) on the eighth day. Cyclooxygenase 2 (COX-2) and tumor necrosis factor-α (TNF-α) levels were measured in nerve tissues. Histopathologic evaluation was performed by electron microscopy. Results The mean sciatic function index (SFI) scores of groups 1 to 4 were +3.27 (standard deviation [SD] ±4.66),–18.2 (SD = ±11.7),–8.5 (SD = ±7.5), and–2.5 (SD = ±9), respectively. The mean COX-2 values were 0.98 ng/mL (SD = ±0.51), 1.89 ng/mL (SD = ±0.22), 1.39 ng/mL (SD = ±0.36), and 1.35 ng/mL (SD = ±0.59), respectively. TNF-α values were 0.09 pg/mL (SD = ±0.23), 1 pg/mL (SD = ±0.96), 0.46 pg/mL (SD = ±0.55), and 0.48 pg/mL (SD = ±0.78), respectively. Group 1 showed normal histologic findings. Group 2 showed marked edema particularly in large-diameter myelins. Myelin configurations were detected in large myelinated axons in group 3. The number of mast cells in endoneurium was high in group 4. Conclusion The efficacy of memantine in the acute phase of PNI appears to be significant according to the SNFI and biochemical tests. However, histologic findings suggest that high doses of memantine have a negative effect on PNI.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Yasar Yildirim ◽  
Esma Gulsum Cellad ◽  
Ali Veysel Kara ◽  
Zülfükar Yilmaz ◽  
Ali Kemal Kadiroglu ◽  
...  

Our aim was to evaluate effect of etanercept on oxidative stress parameters in rats with experimental peritonitis and investigate the availability of etanercept usage in the treatment of peritonitis in the future. Twenty-eight rats were divided into four groups as control (group 1), peritonitis (group 2), peritonitis + cefazolin sodium (group 3), and peritonitis + cefazolin sodium + etanercept (group 4). Peritoneal tissue and blood samples were taken from all of the rats for histopathological and biochemical examination. The oxidative stress parameters were examined in blood and tissue samples. It was observed that rats with peritonitis benefit from cefazolin sodium treatment. Evaluating the effectiveness of etanercept was our main objective for this study. In this perspective, we compared group 3 and group 4 and found statistically significant decreases in oxidative parameters and statistically significant increases in antioxidants in serum and tissue samples in group 4. It is observed that there was a significant contribution of etanercept on biochemical and also histopathological results. As a result, the TNF-αinhibitor, etanercept, in addition to antibiotics given in the early treatment of peritonitis results in more significant improvement of histopathological and oxidative parameters as compared to antibiotics alone.


Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1391
Author(s):  
Yen-Ta Chen ◽  
Kuan-Hui Huang ◽  
John Y. Chiang ◽  
Pei-Hsun Sung ◽  
Chi-Ruei Huang ◽  
...  

This study tested the hypothesis that extracorporeal-shock-wave (ECSW) protected the functional and anatomical integrity of rat urinary-bladder against ketamine-induced damage. In in vitro study, the rat bladder smooth muscle cells (RBdSMCs) were categorized into G1 (sham-control), G2 (RBdSMCs + menadione), G3 (RBdSMCs + ECSW) and G4 (RBdSMCs + menadione + ECSW). The results showed protein expressions of oxidative-stress/mitochondrial-damaged biomarkers (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D), inflammatory markers (MyD88/TRAF6/p-IKB-α/NF-κB/TNF-α/IL-6/IL-1ß/MMP-9/iNOS), and cell-stress response signalings (ASK1/p-MKK4/p-MKK7/ERK1/2//p-JNK/p-p38/p-53) were significantly increased in G2 than in G1 and G3, and those were significantly reversed in G4 (all p < 0.0001). Adult-male SD rats (n = 24) were equally categorized into group 1 (sham-control), group 2 (ketamine/30 mg/kg/daily i.p. injection for four weeks), group 3 [ketamine/30 mg/kg + ECSW/optimal energy (0.12 mJ/mm2/120 impulses/at 3 h and days 3/7/14/21/28 after ketamine administration)] and group 4 [(ketamine/30 mg/kg + ECSW/higher energy (0.16 mJ/mm2/120 impulses)] and animals were euthanized by day 42. The results showed the urine levels of pro-inflammatory cytokines (TNF-α/IL-6) were lowest in group 1, highest in group 2 and significantly higher in group 3 than in group 4 at days 1/7/14/28 (all p < 0.0001). The duration of urinary bladder contraction was lowest in group 2, highest in group 1 and significantly higher in group 4 than in group 3, whereas the maximal pressure of urinary bladder exhibited an opposite pattern of bladder contraction among the groups (all p < 0.0001). The histopathological findings of fibrosis/inflammation/keratinization and protein expressions of oxidative-stress/mitochondrial-damaged biomarkers (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D), and inflammatory (TLR-2/TLR-4/MyD88/TRAF6/p-IKB-α/NF-κB/TNF-α/IL-1ß/MMP-9/iNOS) and cell-stress response (ASK1/p-MKK4/p-MKK7/ERK1/2//p-JNK/p-p38) signalings and apoptotic/fibrotic biomarkers (cleaved-caspas3/cleaved-PARB/Smad3/TFG-ß) exhibited an identical pattern of urine proinflammatory cytokine among the groups (all p < 0.0001). ECSW effectively attenuated ketamine-induced bladder damage and dysfunction.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y C Li ◽  
F Y Lee ◽  
S Chua ◽  
H K Yip

Abstract Intracerebral hemorrhage (ICH) causes 10%-20% of all strokes and results in higher morbidity compared to other subtypes of cerebral stroke. Although early surgical intervention can clear the expanding hematoma, clinical outcomes following ICH have not significantly improved over the decades. Since ICH elicits neuroinflammation to exacerbate brain edema, damage the blood-brain barrier (BBB), lead to secondary neuronal injury, anti-inflammation may be a critical therapeutic strategy. Mesenchymal stem cell (MSC) therapy processes anti-inflammatory, immunomodulatory and tissue regenerative properties, suggesting that MSC therapy could be an effective therapy for ICH. Therefore, this study tested the hypothesis that human induced pluripotent stem cell-derived mesenchymal stem cell (iPSC-MSC) therapy could effectively reduce brain-infract volume (BIV) and improve neurological function in rat after acute ICH induced by a weight-drop device. Adult-male SD rats (n=40) were equally divided into group 1 (sham-operated control), group 2 (ICH), group 3 (ICH + hyaluronic acid (HA)/intracranial injection/3h after ICH), group 4 [ICH + HA + iPSC-MSC (1.2x106 cells/intracranial injection/3h after ICH)] and euthanized by day 28 after ICH procedure. In vitro study showed that hemorrhagic-brain tissue augmented protein expressions of inflammation (HMGB1/MyD88/TLR-4/TLR-2/NF-κB/TNF-α/iNOS/IL-1β) in cultured neurons that were significantly inhibited by iPSC-MSC treatment (all p<0.001). By days 7/14 after ICH procedure, circulating inflammatory levels of TNF-α/IL-6/MPO expressed were lowest in group 1, highest in group 2 and significantly lower in group 4 than in group 3 (all p<0.0001). By day 14 after ICH procedure, neurological function and BIV expressed an opposite pattern, whereas protein expressions of inflammation (HMGB1/MyD88/TLR-4/TLR-2/NF-κB/I-kB/TNF-α/iNOS/IL-1β/MMP-9), oxidative stress (NOX-1/NOX-2/oxidized protein) and apoptosis (mitochondrial-Bax/cleaved-caspase-2/PARP) in brain exhibited an identical pattern to circulating inflammation among the four groups (all p<0.001). Microscopy demonstrated that the number of vascular remodeling/GFAP+/53BP1+/γ-H2AX+ cells displayed an identical pattern of inflammation, whereas the NeuN+ cells displayed an opposite pattern of inflammation among the four groups (all p<0.001). In conclusion, iPSC-MSC therapy markedly reduced BIV and preserved neurological function mainly by inhibiting inflammatory/oxidative-stress generation. Acknowledgement/Funding Kaohsiung Chang Gung Memorial Hospital, Taiwan Society of Stem Cell Research


2020 ◽  
pp. 096032712096077
Author(s):  
MA Ibrahim ◽  
MASA Haleem ◽  
SA AbdelWahab ◽  
AM Abdel-Aziz

Alzheimer disease (AD) is a chronic neurodegenerative disease with multi-pathways pathogenesis. Sildenafil is a selective phosphodiesterase-5 inhibitor with a potential benefit in the treatment of AD. This study investigated the possible mechanisms underlying the effect of sildenafil in AD with emphasis on vascular endothelial growth factor (VEGF), and vascular cell adhesion molecule-1 (VCAM-1). Twenty-four adult male rats were classified into four groups; control group: received vehicles, sildenafil–control: received sildenafil (15 mg/kg/day, p.o.), AD group received Aluminum (25 mg/kg/day, p.o.), AD-treated group: received sildenafil (15 mg/kg/day, p.o.) for 6 weeks. AD was assessed by memory performance test and confirmed by histopathological examination and immunostaining of, neurogenesis marker nestin and α-synuclein. The levels of VEGF-A, VCAM-1, oxidative stress markers and TNF-α in brain tissue were evaluated. AD rats showed histopathological evidences of AD; along with increased latency time in the memory test. There was a decrease in VEGF-A, and an increase in VCAM-1, TNF-α, and oxidative stress markers. Immunohistochemical study showed a significant increase in α-synuclein and a significant decrease in nestin expressions in brain tissues. Sildenafil administration ameliorated the histopathological changes and decreased latency time. Such effect was associated with a decrease in VCAM-1, TNF-α and oxidative stress as well as an increase in VEGF-A. Sildenafil caused a significant increase in nestin and a decrease in α-synuclein immunostaining. These findings suggested a protective effect of sildenafil via modulation of VEGF-A, and VCAM-1.


Sign in / Sign up

Export Citation Format

Share Document