Protective effects of pentoxifylline in small intestine after ischemia–reperfusion

Objective This study was performed to determine the healing effects of pentoxifylline on molecular responses and protection against severe ischemic damage in the small intestine. Methods Thirty-six Wistar albino rats were divided into six groups. The superior mesenteric artery was clamped for 120 minutes, and reperfusion was performed for 60 minutes. Saline (0.4 mL), pentoxifylline (1 mg/kg), and pentoxifylline (10 mg/kg) were intraperitoneally administered to the rats in the C1, P1, and P3 groups, respectively, 60 minutes before ischemia and to the rats in the C2, P2, and P4 groups, respectively, during reperfusion onset. Malondialdehyde, myeloperoxidase, tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 in serum and tissue were measured by enzyme-linked immunosorbent assay. Intestinal ischemic injury was histopathologically evaluated by the Chiu score and immunohistochemical staining. Results All serum and tissue molecular responses were significantly blunted in the pentoxifylline-treated groups compared with the controls. Significant improvement in ischemic damage was demonstrated in the pentoxifylline-treated groups by histological grading and immunohistochemical scoring. Conclusions The protective effects of pentoxifylline were confirmed by molecular responses and histopathological examination.

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Protective Effects of Hypericum perforatum and Quercetin in a Rat Model of Ischemia/Reperfusion Injury of Testes

European Journal of Pediatric Surgery ◽

10.1055/s-0037-1604397 ◽

2017 ◽

Vol 28 (01) ◽

pp. 096-100

Author(s):

Leyla Tekin ◽

Mehmet Erdemli ◽

Nazile Erturk ◽

Zeynep Aksungur ◽

Serdar Aktas ◽

...

Keyword(s):

Antioxidant Status ◽

Hypericum Perforatum ◽

Ischemia Reperfusion Injury ◽

Histopathological Examination ◽

Ischemia Reperfusion ◽

Total Antioxidant Status ◽

Albino Rats ◽

Protective Effects ◽

Total Antioxidant ◽

Markers Of Oxidative Stress

Purpose This study aimed to compare the protective effects of Hypericum perforatum (Hp) and quercetin, a flavonoid, against ischemia/reperfusion (I/R) injury in rat testes. Materials and Methods This study included 28 male Wistar albino rats that were divided into four groups. Except for the sham group, torsion was created by rotating both testes at an angle of 720 degrees clockwise for 2 hours. The Hp and quercetin groups received 25 mg/kg Hp and quercetin intraperitoneally 30 minutes before detorsion, respectively. Orchiectomy was performed for the measurement of markers of oxidative stress and histopathological examination. Results In the Hp and quercetin groups, malondialdehyde (MDA) and nitric oxide (NO) levels and total oxidant capacity were significantly lower, the glutathione level and total antioxidant status were significantly higher, and Johnsen's testis biopsy scores were significantly higher than in the torsion/detorsion group (p ˂ 0.001). The markers of oxidative injury were significantly lower (p ˂ 0.001) and total antioxidant status was significantly higher (p ˂ 0.001), except for glutathione (p = 0.62) in the Hp group than in the quercetin group. Johnsen's score between Hp and quercetin groups was not significantly different (p = 0.80). Conclusion Both Hp and quercetin have protective effects against I/R injury of the testes, but the protective effect of Hp was found to be stronger than that of quercetin.

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Adalimumab Ameliorates Abdominal Aorta Cross Clamping Which Induced Liver Injury in Rats

BioMed Research International ◽

10.1155/2014/907915 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Erkan Cure ◽

Medine Cumhur Cure ◽

Levent Tumkaya ◽

Yildiray Kalkan ◽

Ibrahim Aydin ◽

...

Keyword(s):

Liver Injury ◽

Abdominal Aorta ◽

Liver Tissue ◽

Cell Damage ◽

Ischemia Reperfusion ◽

Control Group ◽

Albino Rats ◽

Protective Effects ◽

Necrosis Factor Alpha ◽

Protein Levels

The aim of this study was to investigate the possible protective effects of adalimumab (ADA) on cell damage in rat liver tissue during ischemia/reperfusion (I/R) injury of infrarenal abdominal aorta. Thirty male Wistar-albino rats were divided into three groups: control, I/R, and I/R+ADA, each group containing 10 animals. Laparotomy without I/R injury was performed in the control group animals. Laparotomy in the I/R group was followed by two hours of infrarenal abdominal aortic cross ligation and then two hours of reperfusion. ADA (50 mg/kg) was administered intraperitoneally as a single dose, to the I/R+ADA group, five days before I/R. The tumor necrosis factor-alpha (TNF-α) (pg/mg protein) and nitric oxide (NO) (µmol/g protein) levels in the I/R group (430.8 ± 70.1, 8.0 ± 1.1, resp.) were significantly higher than those in the I/R+ADA group (338.0 ± 71.6,P=0.006; 6.3 ± 1.2,P=0.008) and the control group (345.5 ± 53.3,P=0.008; 6.5 ± 1.5,P=0.010, resp.). I/R causes severe histopathological injury to the liver tissue, but ADA leads to much less histopathological changes. ADA treatment significantly decreased the severity of liver I/R injury. ADA pretreatment may have protective effects on experimental liver injury.

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Oxydative stress markers and cytokine levels in rosuvastatin-medicated hypercholesterolemia patients

Turkish Journal of Biochemistry ◽

10.1515/tjb-2018-0267 ◽

2018 ◽

Vol 44 (4) ◽

pp. 530-538

Author(s):

Aysun Çetin ◽

İhsan Çetin ◽

Semih Yılmaz ◽

Ahmet Şen ◽

Göktuğ Savaş ◽

...

Keyword(s):

Oxidative Stress ◽

Interleukin 1 ◽

Paraoxonase 1 ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Phenotypic Effect ◽

Necrosis Factor Alpha ◽

Stress Markers ◽

Tnf Α ◽

Before And After

Abstract Background Limited research is available concerning the relationship between oxidative stress and inflammation parameters, and simultaneously the effects of rosuvastatin on these markers in patients with hypercholesterolemia. We aimed to investigate the connection between cytokines and oxidative stress markers in patients with hypercholesterolemia before and after rosuvastatin treatment. Methods The study consisted of 30 hypercholesterolemic patients diagnosed with routine laboratory tests and 30 healthy participants. The lipid parameters, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), paraoxonase-1 (PON1) and malondialdehyde (MDA) levels in controls and patients with hypercholesterolemia before and after 12-week treatment with rosuvastatin (10 mg/kg/day), were analyzed by means of enzyme-linked immunosorbent assay. Results It was found that a 12-week cure with rosuvastatin resulted in substantial reductions in IL-1β, IL-6 and TNF-α and MDA levels as in rising activities of PON1 in patients with hypercholesterolemia. Before treatment, the PON1 levels were significantly negatively correlated with TNF-α and IL-6 in control group, while it was positively correlated with TNF-α in patients. Conclusion Our outcomes provide evidence of protected effect of rosuvastatin for inflammation and oxidative damage. It will be of great interest to determine whether the correlation between PON1 and cytokines has any phenotypic effect on PON1.

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Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000495926 ◽

2018 ◽

Vol 51 (6) ◽

pp. 2575-2590 ◽

Cited By ~ 15

Author(s):

Gang Zhong ◽

Ruiming Liang ◽

Jun Yao ◽

Jia Li ◽

Tongmeng Jiang ◽

...

Keyword(s):

Signaling Pathway ◽

Cruciate Ligament ◽

Interleukin 1 ◽

Cartilage Degradation ◽

Chondrocyte Apoptosis ◽

Enzyme Linked Immunosorbent Assay ◽

Cell Viability Assay ◽

Necrosis Factor Alpha ◽

Anti Inflammatory

Background/Aims: Current drug therapies for osteoarthritis (OA) are not practical because of the cytotoxicity and severe side-effects associated with most of them. Artemisinin (ART), an antimalarial agent, is well known for its safety and selectivity to kill injured cells. Based on its anti-inflammatory activity and role in the inhibition of OA-associated Wnt/β-catenin signaling pathway, which is crucial in the pathogenesis of OA, we hypothesized that ART might have an effect on OA. Methods: The chondro-protective and antiarthritic effects of ART on interleukin-1-beta (IL-1β)-induced and OA patient-derived chondrocytes were investigated in vitro using cell viability assay, glycosaminoglycan secretion, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blotting. We also used OA model rats constructed by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) in the joints to investigate the effects of ART on OA by gross observation, morphological staining, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ART exhibited potent anti-inflammatory effects by inhibiting the expression of proinflammatory chemokines and cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha, and matrix metallopeptidase-13. It also showed favorable chondro-protective effect as evidenced by enhanced cell proliferation and viability, increased glycosaminoglycan deposition, prevention of chondrocyte apoptosis, and degeneration of cartilage. Further, ART inhibited OA progression and cartilage degradation via the Wnt/β-catenin signaling pathway, suggesting that it might serve as a Wnt/β-catenin antagonist to reduce inflammation and prevent cartilage degradation. Conclusion: In conclusion, ART alleviates IL-1β-mediated inflammatory response and OA progression by regulating the Wnt/β-catenin signaling pathway. Thereby, it might be developed as a potential therapeutic agent for OA.

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Prolonged Helium Postconditioning Protocols during Early Reperfusion Do Not Induce Cardioprotection in the Rat HeartIn Vivo: Role of Inflammatory Cytokines

Journal of Immunology Research ◽

10.1155/2015/216798 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Gezina Tanya Mei Ling Oei ◽

Hamid Aslami ◽

Raphaela Priscilla Kerindongo ◽

Renske Johanna Steenstra ◽

Charlotte Jacqueline Peter Beurskens ◽

...

Keyword(s):

Infarct Size ◽

Inflammatory Cytokines ◽

Noble Gas ◽

Ischemia Reperfusion ◽

Interleukin 1 ◽

Myocardial Tissue ◽

Mrna Levels ◽

Necrosis Factor Alpha ◽

Early Reperfusion ◽

Protein Levels

Postconditioning of myocardial tissue employs short cycles of ischemia or pharmacologic agents during early reperfusion. Effects of helium postconditioning protocols on infarct size and the ischemia/reperfusion-induced immune response were investigated by measurement of protein and mRNA levels of proinflammatory cytokines. Rats were anesthetized with S-ketamine (150 mg/kg) and diazepam (1.5 mg/kg). Regional myocardial ischemia/reperfusion was induced; additional groups inhaled 15, 30, or 60 min of 70% helium during reperfusion. Fifteen minutes of helium reduced infarct size from 43% in control to 21%, whereas 30 and 60 minutes of helium inhalation led to an infarct size of 47% and 39%, respectively. Increased protein levels of cytokine-induced neutrophil chemoattractant (CINC-3) and interleukin-1 beta (IL-1β) were found after 30 or 60 min of helium inhalation, in comparison to control. 30 min of helium increased mRNA levels of CINC-3, IL-1β, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in myocardial tissue not directly subjected to ischemia/reperfusion. These results suggest that the effectiveness of the helium postconditioning protocol is very sensitive to duration of noble gas application. Additionally, helium was associated with higher levels of inflammatory cytokines; however, it is not clear whether this is causative of nature or part of an epiphenomenon.

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Guaiane-Type Sesquiterpenoids From Dendranthema morifolium (Ramat.) S. Kitam Flowers Protect H9c2 Cardiomyocyte From LPS-Induced Injury

Natural Product Communications ◽

10.1177/1934578x19864179 ◽

2019 ◽

Vol 14 (7) ◽

pp. 1934578X1986417

Author(s):

Beibei Zhang ◽

Mengnan Zeng ◽

Meng Li ◽

Wenjing Chen ◽

Benke Li ◽

...

Keyword(s):

Caspase 3 ◽

Creatine Phosphate ◽

Cardiomyocyte Apoptosis ◽

Exocyclic Double Bond ◽

Enzyme Linked Immunosorbent Assay ◽

Protective Effects ◽

Caspase 9 ◽

Necrosis Factor Alpha ◽

Thiazolyl Blue Tetrazolium Bromide ◽

Tnf Α

This study investigated the protective effects of guaiane-type sesquiterpenoids isolated from Dendranthema morifolium (Ramat.) S. Kitam ﬂowers on lipopolysaccharide (LPS)-induced injury in H9c2 cardiomyocyte. Cell viability was determined by thiazolyl blue tetrazolium bromide (MTT). The content of released tumor necrosis factor alpha (TNF- α) and interleukin 6 (IL-6) was evaluated by enzyme-linked immunosorbent assay. The levels of lactate dehydrogenase (LDH) and creatine phosphate kinase (CK) were measured by using commercial available kits. The protein expression levels of pelF2 α, GRP78, Bax, caspase-3, caspase-9, Bcl-2, LC3-II, and p62 were measured by in-cell Western. Flow cytometry was used to detect H9c2 cardiomyocyte apoptosis. Compounds 5, 7, 1, 8, and 2 exhibited the effects of cardioprotection and activity sequence enhancement. The levels of IL-6, TNF- α, LDH, CK, pelF2 α, GRP78, Bax, caspase-3, caspase-9, p62, and H9c2 cardiomyocyte apoptosis were increased in LPS-treated H9c2 cardiomyocyte, while those of Bcl-2 and LC3-II were decreased. These effects could be effectively reversed by compounds 5, 7, 1, 8, and 2. Results demonstrated that the guaiane-type sesquiterpenoids could prevent LPS-induced injury in cardiomyocyte by decreasing endoplasmic reticulum (ER) stress, apoptosis, and autophagy as well as downregulating the inflammatory mediators. In addition, the active groups of guaiane-type sesquiterpenoids might be the angelate at C-8 and the exocyclic double bond at C-11.

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Impact of Coenzyme Q10 Administration on Lead Acetate-Induced Testicular Damage in Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/4981386 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Manal El-khadragy ◽

Wafa A. Al-Megrin ◽

Norah A. AlSadhan ◽

Dina M. Metwally ◽

Rehab E. El-Hennamy ◽

...

Keyword(s):

Coenzyme Q10 ◽

Lead Acetate ◽

Interleukin 1 ◽

Tween 80 ◽

Control Group ◽

Protective Effects ◽

Necrosis Factor Alpha ◽

Coq10 Supplementation ◽

Induced Apoptosis ◽

Testicular Injury

Exposure to lead (Pb) causes multiorgan dysfunction including reproductive impairments. Here, we examined the protective effects of coenzyme Q10 (CoQ10) administration on testicular injury induced by lead acetate (PbAc) exposure in rats. This study employed four experimental groups (n=7) that underwent seven days of treatment as follows: control group intraperitoneally (i.p.) treated with 0.1 ml of 0.9% NaCl containing 1% Tween 80 (v:v), CoQ10 group that was i.p. injected with 10 mg/kg CoQ10, PbAc group that was i.p. treated with PbAc (20 mg/kg), and PbAc+CoQ10 group that was i.p. injected with CoQ10 2 h after PbAc. PbAc injection resulted in increasing residual Pb levels in the testis and reducing testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Additionally, PbAc exposure resulted in significant oxidative damage to the tissues on the testes. PbAc raised the levels of prooxidants (malondialdehyde and nitric oxide) and reduced the amount of endogenous antioxidative proteins (glutathione and its derivative enzymes, catalase, and superoxide dismutase) available in the cell. Moreover, PbAc induced the inflammatory response as evidenced by the upregulation of inflammatory mediators (tumor necrosis factor-alpha and interleukin-1 beta). Further, PbAc treatment induced apoptosis in the testicular cells, as indicated by an increase in Bax and caspase 3 expression, and reduced Bcl2 expression. CoQ10 supplementation improved testicular function by inhibiting Pb accumulation, oxidative stress, inflammation, cell death, and histopathological changes following PbAc exposure. Our findings suggest that CoQ10 can act as a natural therapeutic agent to protect against the reproductive impairments associated with PbAc exposure.

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ERK1/2-Egr-1 Signaling Pathway-Mediated Protective Effects of Electroacupuncture in a Mouse Model of Myocardial Ischemia-Reperfusion

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/253075 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Juan Zhang ◽

Jiangang Song ◽

Jin Xu ◽

Xuemei Chen ◽

Peihao Yin ◽

...

Keyword(s):

Myocardial Ischemia ◽

Signaling Pathway ◽

Target Genes ◽

Troponin I ◽

Inflammatory Responses ◽

Ischemia Reperfusion ◽

Interleukin 1 ◽

Protective Effects ◽

Downstream Target ◽

Myocardial Ischemia Reperfusion

Early growth response- (Egr-) 1 is an upstream master switch in controlling inflammatory responses following myocardial ischemia-reperfusion (I/R). Activation of extracellular signal-regulated protein kinase-1 and kinase-2 (ERK1/2) signaling is known to upregulate Egr-1. ERK1/2 pathway has been previously shown to mediate the therapeutic action of electroacupucture (EA). Thus, we hypothesized that EA would reduce myocardial I/R injury and inflammatory responses through inhibiting Egr-1 expression via the ERK1/2 pathway. Mice were pretreated with EA, U0126, or combination of EA and U0126 and then underwent 1 h myocardial ischemia and 3 h reperfusion. We investigated that EA significantly attenuated the I/R-induced upregulation of both Egr-1 and phosporylated-ERK1/2 (p-ERK1/2), decreased myocardial inflammatory cytokines including tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β), and reduced the infarct size and the release of cardiac troponin I (cTnI). U0126 treatment also exhibited the same effect as EA on Egr-1 level and subsequent cardioprotective effects. There was no additive effect of cotreatment with EA and U0126 on the expression of Egr-1 and its downstream target genes (TNF-α, IL-1β) or serum cTnI level. Collectively, these observations suggested that EA attenuates myocardial I/R injury, possibly through inhibiting the ERK1/2-Egr-1 signaling pathway and reducing the release of proinflammatory cytokines.

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Apigenin ameliorates ocular surface lesions in a rat model of dry eye disease

European Journal of Inflammation ◽

10.1177/2058739218818681 ◽

2019 ◽

Vol 17 ◽

pp. 205873921881868

Author(s):

Limei Liu ◽

Dongdong Wei ◽

Hongkun Xu ◽

Changhui Liu

Keyword(s):

Dry Eye ◽

Ocular Surface ◽

Histopathological Examination ◽

Tear Film ◽

Interleukin 10 ◽

Dry Eye Disease ◽

Eye Disease ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Necrosis Factor Alpha

To study the effects of apigenin on dry eye disease (DED) in rats. Rats were divided into six groups: (I) normal control group, (II) DED control group, (III) vehicle control group, (IV) DED + apigenin 10 mg/kg, (V) DED + apigenin 20 mg/kg, and (VI) DED + apigenin 50 mg/kg. Schirmer test, tear film break-up time (BUT), and corneal fluorescein staining were used to evaluate the effects of apigenin on the ocular surface. The related inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Histopathological examination and inflammatory index were also performed. The results showed that administration of apigenin was shown a significant effect on the recovery of ocular surface function. Compared to the control group, apigenin treatment in DED rats significantly decreased the level of the tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6); however, the interleukin-10 (IL-10) level was increased. Histopathological examination further verified the anti-inflammatory effects of apigenin on DED rats. The results demonstrated that apigenin could protect DED rats via inhibition of inflammation, suggesting that it may have potential as a therapy for DED.

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Immunomodulating effect of fosfomycin on gut-derived sepsis caused by Pseudomonas aeruginosa in mice.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.2.308 ◽

1997 ◽

Vol 41 (2) ◽

pp. 308-313 ◽

Cited By ~ 27

Author(s):

T Matsumoto ◽

K Tateda ◽

S Miyazaki ◽

N Furuya ◽

A Ohno ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Survival Rate ◽

Protective Effect ◽

Specific Activity ◽

Bacterial Colonization ◽

Interleukin 1 ◽

Protective Mechanism ◽

Protective Effects ◽

Bacterial Clearance ◽

Necrosis Factor Alpha

We evaluated the protective effect of fosfomycin (FOM) and an enantiomer of fosfomycin [FOM (+); an isomer of FOM with no bactericidal activity] on murine gut-derived sepsis caused by Pseudomonas aeruginosa. Endogenous bacteremia was induced by administering cyclophosphamide (CY) and ampicillin to specific-pathogen-free mice fed P. aeruginosa. Treatment of mice with FOM at 250 mg/kg of body weight per day twice a day after the second CY administration significantly increased the survival rate compared to that for control mice treated with saline. Treatment with FOM (+) at 20 and 100 mg/kg also significantly increased the survival rate (from 30% for control mice to 80% for treated mice). The bacterial counts in the liver and blood were both significantly lower in FOM(+)-treated mice in comparison with those in liver and blood of saline-treated control mice. FOM(+) administration affected neither the bacterial colonization in the intestinal tract nor the leukocyte counts in the peripheral blood of the mice. After intravascular inoculation of P. aeruginosa, treatment of mice with FOM (+) did not enhance bacterial clearance from the blood of mice pretreated or not enhance bacterial clearance from the blood of mice pretreated or not pretreated with CY, FOM(+) significantly suppressed tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 levels in the serum of mice after gut-derived sepsis. These results indicate that both FOM and FOM(+) have protective effects against P. aeruginosa bacteremia, despite a lack of specific activity of FOM(+), and suggest that FOM may possess immunomodulating activity and that it induces a protective effect. The protective mechanism is speculated to be that FOM modulates the vivo production of inflammatory cytokines.

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