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Chemoprevention with a tea from hawthorn ( Crataegus oxyacantha) leaves and flowers attenuates colitis in rats by reducing inflammation and oxidative stress
The purpose of the study was to determine the effects of a tea from the leaves and flowers of Crataegus oxyacantha in rats with colitis. Colitis was induced by administration of 2,4,6-trinitrobenzene sulfonic acid. Hawthorn tea (HT) (100 mg/kg) was given via gavage for 21 days and the mesalamine drug (100 mg/kg) was administrated during the period of disease onset.
HT was rich in total phenolic compounds (16.5%), flavonoids (1.8%), and proanthocyanidins (1.5%); vitexin-2-O-rhamnoside was the main compound detected. Mesalamine and the HT diminished the length of the lesions formed in the colon, in addition to reducing the levels of myeloperoxidase and interleukin-1β.
Mesalamine was able to significantly reverse the body weight loss, while HT improved the activity of glutathione reductase and catalase. Histological scoring was not changed by the interventions, but it was highly correlated with the necrotic area. HT given at 100 mg/kg can be effective against colitis.
Protective Effects of Low-Dose Alcohol against Acute Stress-Induced Renal Injury in Rats: Involvement of CYP4A/20-HETE and LTB 4/BLT1 Pathways
Low-dose alcohol possesses multiple bioactivities. Accordingly, we investigated the protective effect and related molecular mechanism of low-dose alcohol against acute stress- (AS-) induced renal injury. Herein, exhaustive swimming for 15 min combined with restraint stress for 3 h was performed to establish a rat acute stress model, which was verified by an open field test.
Evaluation of renal function (blood creatinine and urea nitrogen), urine test (urine leukocyte esterase and urine occult blood), renal histopathology, oxidative stress, inflammation, and apoptosis was performed. The key indicators of the cytochrome P450 (CYP) 4A1/20-hydroxystilbenetetraenoic acid (20-HETE) pathway, cyclooxygenase (COX)/prostaglandin E2 (PGE2) pathway, and leukotriene B4 (LTB4)/leukotriene B4 receptor 1 (BLT1) pathway were measured by real-time PCR and ELISA.
We found that low-dose alcohol (0.05 g/kg, i.p.) ameliorated AS-induced renal dysfunction and histological damage. Low-dose alcohol also attenuated AS-induced oxidative stress and inflammation, presenting as reduced malondialdehyde and hydrogen peroxide formation, increased superoxide dismutase and glutathione activity, and decreased myeloperoxidase, interleukin-6, interleukin-1β, and monocyte chemoattractant protein-1 levels (P < 0.05).
Moreover, low-dose alcohol alleviated AS-induced apoptosis by downregulating Bax and cleaved caspase 3 protein expression and reduced numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick-end label-positive cells (P < 0.01).
Correlation analysis indicated that 20-HETE was strongly correlated with oxidative stress, while LTB4 was strongly correlated with inflammation. Low-dose alcohol inhibited AS-induced increases in CYP4A1, CYP4A2, CYP4A3, CYP4A8, and BLT1 mRNA levels and LTB4 and 20-HETE content (P < 0.01).
Interestingly, low-dose alcohol had no effect on COX1 or COX2 mRNA expression or the concentration of PGE2. Furthermore, low-dose alcohol reduced calcium-independent phospholipase A2 mRNA expression, but did not affect secreted phospholipase A2 or cytosolic phospholipase A2 mRNA expression. Together, these results indicate that low-dose alcohol ameliorated AS-induced renal injury by inhibiting CYP4A/20-HETE and LTB4/BLT1 pathways, but not the COX/PGE2 pathway.
Neutrophils Isolated from Septic Patients Exhibit Elevated Uptake of Vitamin C and Normal Intracellular Concentrations despite a Low Vitamin C Milieu
Vitamin C (ascorbate) plays an important role in neutrophil function and is accumulated by the cells either directly via vitamin C transporters (SVCT) or indirectly following oxidation to dehydroascorbic acid. Septic patients are known to have significantly depleted plasma ascorbate status, but little is known about the ascorbate content of their circulating cells.
Therefore, we assessed the ascorbate concentrations of plasma, leukocytes and erythrocytes from septic patients and compared these to healthy controls. Non-fasting blood samples were collected from healthy volunteers (n = 20) and critically ill patients with sepsis (n = 18). The ascorbate content of the plasma and isolated neutrophils and erythrocytes was measured using HPLC and plasma myeloperoxidase concentrations were determined using ELISA.
Ex vivo uptake of ascorbate and dehydroascorbic acid by neutrophils from septic patients was also assessed. Neutrophils isolated from septic patients had comparable intracellular ascorbate content to healthy volunteers (0.33 vs. 0.35 nmol/106 cells, p > 0.05), despite significantly lower plasma concentrations than the healthy controls (14 vs. 88 µmol/L, p < 0.001).
In contrast, erythrocytes from septic patients had significantly lower intracellular ascorbate content than healthy controls (30 vs. 69 µmol/L, p = 0.002), although this was 2.2-fold higher than the matched plasma concentrations in the patients (p = 0.008). Higher concentrations of myeloperoxidase, a source of reactive oxygen species, were observed in the septic patients relative to healthy controls (194 vs. 14 mg/mL, p < 0.0001).
In contrast to neutrophils from healthy volunteers, the neutrophils from septic patients demonstrated elevated uptake of extracellular ascorbate. Overall, neutrophils from septic patients exhibited comparable intracellular ascorbate content to those from healthy controls, despite the patients presenting with hypovitaminosis C. The mechanisms involved are currently uncertain, but could include increased generation of dehydroascorbic acid in septic patients, enhanced basal activation of their neutrophils or upregulation of their vitamin C transporters.
Manganese mitigates against hepatorenal oxidative stress, inflammation and caspase-3 activation in rats exposed to hexachlorobenzene
The present study investigated the individual and collective effect of organochlorinated fungicide hexachlorobenzene (HCB) and manganese (Mn), a metal, on the hepatorenal function in adult rats. Rats were divided into four groups of rats comprising of control, HCB alone (15 mg/kg), Mn alone (10 mg/kg) and co-exposure group that were orally treated for 25 consecutive days.
After sacrifice, hepatorenal damage and antioxidant status markers, myeloperoxidase (MPO) activity, levels of nitric oxide, total antioxidant capacity (TAC), total oxidative stress (TOS) and lipid peroxidation (LPO) were analyzed spectrophotometrically. Levels of tumor necrosis factor alpha (TNF-α), interleukin-1 β (IL-1β) and caspase-3 activity were assessed using ELISA.
Results revealed that the HCB administration significantly (p < 0.05) increased the biomarkers of hepatorenal toxicity, decreased the antioxidant status and TAC, raised the levels of TOS and LPO as well as increased the levels of TNF-α, IL-1β and caspase-3 activity. Rats co-exposed to HCB and Mn showed decreased biomarkers of hepatorenal damage, increased antioxidant status and TAC with simultaneous reduction in the levels of TOS and LPO significantly (p < 0.05).
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (APC) |
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MBS6323232-02mL | MyBiosource | 0.2mL | EUR 980 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (APC) |
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MBS6323232-5x02mL | MyBiosource | 5x0.2mL | EUR 4250 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (Biotin) |
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MBS6323233-02mL | MyBiosource | 0.2mL | EUR 980 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (Biotin) |
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MBS6323233-5x02mL | MyBiosource | 5x0.2mL | EUR 4250 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (FITC) |
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MBS6323234-02mL | MyBiosource | 0.2mL | EUR 980 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (FITC) |
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MBS6323234-5x02mL | MyBiosource | 5x0.2mL | EUR 4250 |
Myeloperoxidase, NT (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (APC) |
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MBS6323243-02mL | MyBiosource | 0.2mL | EUR 980 |
Myeloperoxidase, NT (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (APC) |
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MBS6323243-5x02mL | MyBiosource | 5x0.2mL | EUR 4250 |
Myeloperoxidase, NT (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (Biotin) |
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MBS6323244-02mL | MyBiosource | 0.2mL | EUR 980 |
Myeloperoxidase, NT (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (Biotin) |
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MBS6323244-5x02mL | MyBiosource | 5x0.2mL | EUR 4250 |
Myeloperoxidase, NT (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (FITC) |
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MBS6323245-02mL | MyBiosource | 0.2mL | EUR 980 |
Myeloperoxidase, NT (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (FITC) |
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MBS6323245-5x02mL | MyBiosource | 5x0.2mL | EUR 4250 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 405) |
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MBS6323236-01mL | MyBiosource | 0.1mL | EUR 980 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 405) |
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MBS6323236-5x01mL | MyBiosource | 5x0.1mL | EUR 4250 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 490) |
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MBS6323237-01mL | MyBiosource | 0.1mL | EUR 980 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 490) |
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MBS6323237-5x01mL | MyBiosource | 5x0.1mL | EUR 4250 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 550) |
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MBS6323238-01mL | MyBiosource | 0.1mL | EUR 980 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 550) |
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MBS6323238-5x01mL | MyBiosource | 5x0.1mL | EUR 4250 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 650) |
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MBS6323239-01mL | MyBiosource | 0.1mL | EUR 980 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 650) |
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MBS6323239-5x01mL | MyBiosource | 5x0.1mL | EUR 4250 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 750) |
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MBS6323240-01mL | MyBiosource | 0.1mL | EUR 980 |
Myeloperoxidase, ID (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 750) |
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MBS6323240-5x01mL | MyBiosource | 5x0.1mL | EUR 4250 |
Myeloperoxidase, NT (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 405) |
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MBS6323247-01mL | MyBiosource | 0.1mL | EUR 980 |
Myeloperoxidase, NT (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 405) |
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MBS6323247-5x01mL | MyBiosource | 5x0.1mL | EUR 4250 |
Myeloperoxidase, NT (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 490) |
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MBS6323248-01mL | MyBiosource | 0.1mL | EUR 980 |
Myeloperoxidase, NT (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 490) |
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MBS6323248-5x01mL | MyBiosource | 5x0.1mL | EUR 4250 |
Myeloperoxidase, NT (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 550) |
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MBS6323249-01mL | MyBiosource | 0.1mL | EUR 980 |
Myeloperoxidase, NT (MPO, Myeloperoxidase, 89kD myeloperoxidase, 84kD myeloperoxidase, Myeloperoxidase light chain, Myeloperoxidase heavy chain) (MaxLight 550) |
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MBS6323249-5x01mL | MyBiosource | 5x0.1mL | EUR 4250 |
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Furthermore, the increased levels of TNF-α, IL-1β and caspase-3 activity were significantly (p < 0.05) reduced in the liver and kidney of rats’ co-expose to HCB and Mn. Histological examination showed that damages induced by HCB were assuaged in rats co-treated with HCB and Mn. In conclusion, the results demonstrated that co-treatment of HCB and Mn in rats’ alleviated HCB-induced oxidative stress, inflammation and caspase-3 activation in the liver and kidney of the rats.
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