scholarly journals High Doses of Kefir Accelerate Lung-Injury Progression in Bleomycin-Induced Pneumonitis in Rats

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Tri Yudani Mardining Raras ◽  
Nurul Hidayati ◽  
Shinta Oktya Wardhani
Keyword(s):  
Activity Level ◽  
Alveolar Epithelial Cells ◽  
Male Rats ◽  
High Dose ◽  
Intragastric Administration ◽  
Activity Levels ◽  
Alveolar Epithelial ◽  
Lung Structure ◽  
Tnf Α ◽  
High Doses

Background: Bleomycin-induced pneumonitis (BIP) is a common consequence of bleomycin (BLE) use during chemotherapy. Kefir is a probiotic with many health benefits. Many cancer patients in Indonesia consume kefir as a complementary traditional medicine alongside standard chemotherapy. Objectives: This study aimed to investigate the effects of high-dose kefir consumption on BIP in a rat model. Methods: Wistar male rats were given 0.3 mg of BLE via intranasal inhalation for 6 days with a daily intragastric administration of either phosphate buffered saline (PBS) or kefir at dosages of 2.5 mL, 3.5 mL, and 4.5 mL per day for 30 days. On day 30, lung sections were obtained and stained with hematoxylin and eosin for histological examinations. Immunohistochemistry tests were carried out to determine the activity levels of matrix metalloproteinase (MMP)-1, signal transducer, and activator of transcription (STAT)-3. TNF-α and IL-6 concentrations in plasma were also evaluated. Results: Histological results showed damage to the lung structure by inflammation with diffuse infiltrate, with some areas exhibiting slight fibrosis. The number of alveolar epithelial cells expressing MMP-1 significantly increased with the kefir dosage. Interestingly, only the highest dose of kefir raised IL-6 levels, while TNF-α levels increased at all kefir doses. STAT-3 showed a slight increase in activity level. As MMP-1 works to degrade fibrosis while both TNF-α and Il-6 are correlated with inflammation, these findings might explain the observed histological changes in lung structure in the BLE and kefir groups. Conclusions: The administration of high doses of kefir in rats increased the expression of pro-inflammatory cytokines, which worsened BIP.

Lipidomics Study of the Therapeutic Mechanism of Plantaginis Semen in Potassium Oxonate-Induced Hyperuricemia Rat

2020 ◽  
Author(s):  
Wenjun Shi ◽  
Fei Yang ◽  
Liting Wang ◽  
Nankun Qin ◽  
Chengxiang Wang ◽  
...  
Keyword(s):  
Male Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
High Dose ◽  
Intragastric Administration ◽  
Group Model ◽  
Model Group ◽  
Tnf Α ◽  
Plantaginis Semen ◽  
Potassium Oxonate

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable

scholarly journals Lipidomics study of the therapeutic mechanism of Plantaginis Semen in potassium oxonate-induced hyperuricemia rat

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fei Yang ◽  
Wenjun Shi ◽  
Liting Wang ◽  
Nankun Qin ◽  
Chengxiang Wang ◽  
...  
Keyword(s):  
Male Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Intragastric Administration ◽  
Group Model ◽  
Model Group ◽  
Tnf Α ◽  
Therapeutic Mechanism ◽  
Plantaginis Semen ◽  
Potassium Oxonate

Abstract Background Plantaginis Semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but its pharmacological mechanism remains unclear. This study investigated the therapeutic mechanism of Plantaginis Semen extract on potassium oxonate -induced HUA rats based on a lipidomics approach. Methods A model of HUA was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis Semen groups (n = 7). The Plantaginis Semen groups were treated orally with Plantaginis Semen, 0.9375, 1.875  or 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were  measured using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used for the serum lipidomics analysis, multivariate statistical analysis and independent samples t-test were carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors were determined by quantitative real-time polymerase chain reaction (RT-qPCR). Results Compared with the model group, the levels of serum UA, Cr, TG and TNF-α were significantly (p < 0.05) decreased in benzbromarone and three Plantaginis Semen groups. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was  most affected. These perturbations  were partially restored via treatment of benzbromarone and Plantaginis Semen. Additionally, the mRNA expression levels of urate anion transporter 1 (URAT1) and phosphatidylinositol 3-kinase/protein kinases B (PI3K/Akt) were significantly decreased (p < 0.01) after treatment with benzbromarone and high dose of Plantaginis Semen. Conclusions Plantaginis Semen had significant effects on anti-HUA, anti-inflammatory and renal protection. It attenuated potassium oxonate-induced HUA through regulation of lipid metabolism disorder.

Gammaglutamyltransferase activity in buffalo mammary tissue during lactation

2006 ◽  
Vol 82 (3) ◽  
pp. 351-354 ◽  
Author(s):  
M. E. Pero ◽  
N. Mirabella ◽  
P. Lombardi ◽  
C. Squillacioti ◽  
A. De Luca ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Epithelial Cells ◽  
Milk Production ◽  
Milk Protein ◽  
Water Buffalo ◽  
Alveolar Epithelial Cells ◽  
Mammary Tissue ◽  
Activity Levels ◽  
Alveolar Epithelial

AbstractIn the present study, the rôle of gammaglutamyltransferase (GGT) during lactation has been investigated in the water buffalo. GGT activity has been evaluated in the mammary tissue at 4 and 6 months after calving and during the non-lactating period. The highest GGT activity levels were found at day 120 (32·57±7·41 U per g) of lactation and were statistically higher than those at 180 (10·76±3·6 U per g) or during the non-lactating period (9·86±7·94 U per g). Histochemistry confirmed these findings and revealed that GGT reactivity was distributed throughout the cytoplasm of alveolar epithelial cells. Such results showed that the GGT production is high during lactation thus supporting the hypothesis that this enzyme plays a rôle in determining milk production in water buffalo by supporting milk protein synthesis.

scholarly journals The ex vivo perfused human lung is resistant to injury by high-dose S. pneumoniae bacteremia

2020 ◽  
Vol 319 (2) ◽  
pp. L218-L227 ◽  
Author(s):  
James T. Ross ◽  
Nicolas Nesseler ◽  
Aleksandra Leligdowicz ◽  
Rachel L. Zemans ◽  
Rahul Y. Mahida ◽  
...  
Keyword(s):  
Human Lung ◽  
Ex Vivo ◽  
Alveolar Epithelium ◽  
Lung Model ◽  
High Dose ◽  
Alveolar Epithelial ◽  
Low Protein ◽  
Alveolar Epithelial Injury ◽  
High Doses ◽  
Protein Permeability

Few patients with bacteremia from a nonpulmonary source develop acute respiratory distress syndrome (ARDS). However, the mechanisms that protect the lung from injury in bacteremia have not been identified. We simulated bacteremia by adding Streptococcus pneumoniae to the perfusate of the ex vivo perfused human lung model. In contrast to a pneumonia model in which bacteria were instilled into the distal air spaces of one lobe, injection of high doses of S. pneumoniae into the perfusate was not associated with alveolar epithelial injury as demonstrated by low protein permeability of the alveolar epithelium, intact alveolar fluid clearance, and the absence of alveolar edema. Unexpectedly, the ex vivo human lung rapidly cleared large quantities of S. pneumoniae even though the perfusate had very few intravascular phagocytes and lacked immunoglobulins or complement. The bacteria were cleared in part by the small number of neutrophils in the perfusate, alveolar macrophages in the airspaces, and probably by interstitial pathways. Together, these findings identify one mechanism by which the lung and the alveolar epithelium are protected from injury in bacteremia.

scholarly journals LPS-induced depolymerization of cytoskeleton and its role in TNF-α production by rat pneumocytes

1999 ◽  
Vol 277 (3) ◽  
pp. L606-L615 ◽  
Author(s):  
Noritaka Isowa ◽  
Alexandre M. Xavier ◽  
Ewa Dziak ◽  
Michal Opas ◽  
Donna I. McRitchie ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Cells ◽  
Protein Production ◽  
Mrna Level ◽  
Alveolar Epithelial Cells ◽  
Immunofluorescent Staining ◽  
Alveolar Epithelial ◽  
Tnf Α ◽  
Factor Α

Lipopolysaccharide (LPS) polymerizes microfilaments and microtubules in macrophages and monocytes. Disrupting microfilaments or microtubules with cytochalasin D (CytoD) or colchicine can suppress LPS-induced tumor necrosis factor-α (TNF-α) gene expression and protein production from these cells. We have recently demonstrated that primary cultured rat alveolar epithelial cells can produce TNF-α on LPS stimulation. In the present study, we found that the LPS-induced increase in TNF-α mRNA level and protein production in alveolar epithelial cells was not inhibited by CytoD or colchicine (1 nM to 10 μM). In fact, LPS-induced TNF-α production was further enhanced by CytoD (1–10 μM) and inhibited by jasplakinolide, a polymerizing agent for microfilaments. Immunofluorescent staining and confocal microscopy showed that LPS (10 μg/ml) depolymerized microfilaments and microtubules within 15 min, which was prolonged until 24 h for microfilaments. These results suggest that the effects of LPS on the cytoskeleton and the role of the cytoskeleton in mediating TNF-α production in alveolar epithelial cells are opposite to those in immune cells. This disparity may reflect the different roles between nonimmune and immune cells in host defense.

Dynamics of TGF-beta 3 peptide activity during rat alveolar epithelial cell proliferative recovery from acute hyperoxia

1996 ◽  
Vol 271 (1) ◽  
pp. L54-L60 ◽  
Author(s):  
S. Buckley ◽  
K. C. Bui ◽  
M. Hussain ◽  
D. Warburton
Keyword(s):  
Epithelial Cell ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Male Rats ◽  
Brdu Incorporation ◽  
Tgf Beta ◽  
Alveolar Epithelial ◽  
Proliferative Phase ◽  
Oxygen Exposure ◽  
Beta Peptide

Hyperoxia causes a reproducible pattern of lung injury and recovery, characterized by proliferation of type II alveolar epithelial cells (AEC2) during the recovery phase. We measured TGF-beta peptide production by AEC2 and macrophages from lungs of adult male rats exposed to 100% oxygen for 48 h and then allowed to recover for up to 72 h in room air. TGF-beta peptide activity levels were measured using the PAI-1 promoter-luciferase mink lung epithelial cell assay and characterized with peptide specific inhibitory antibodies. Control AEC2 produced 997 +/- 54 pg active TGF-beta x 10(6) cells-1.24h-1 (mean +/- SD), of which > 70% was TGF-beta 3, while cultured macrophages produced 58 +/- 17 pg active TGF-beta x 10(6) macrophages-1.24 h-1, > 80% of which was TGF-beta 1. During hyperoxia and recovery, active TGF-beta 3 production by AEC2 decreased by 75%, with a nadir at 24 h recovery (P < 0.005). In contrast, TGF-beta peptide activity increased from undetectable levels in lung lavage from control rats to a peak of 1,470 +/- 743 pg/rat after 48 h oxygen exposure and 24 h recovery, while lavaged macrophage TGF-beta production in culture also increased threefold to a peak of 150 +/- 5 pg. 10(6) cells-1. 24 h-1 after 48 h oxygen exposure (P < 0.005). The nadir of active TGF-beta 3 production by AEC2 coincided with the peak of the AEC2 proliferative phase of repair as determined by BrdU incorporation and FACS analysis of freshly isolated AEC2. We conclude that active TGF-beta 3 production by AEC2 is dynamically downregulated during the proliferative phase of recovery from acute hyperoxic injury in rat. We speculate that decreased autocrine negative regulation of AEC2 proliferation by TGF-beta 3 may facilitate AEC2 proliferation during recovery from acute hyperoxic injury.

scholarly journals Activation of M1 macrophages plays a critical role in the initiation of acute lung injury

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Hui-Lun Lu ◽  
Xin-Yan Huang ◽  
Yi-Feng Luo ◽  
Wei-Ping Tan ◽  
Pei-Fen Chen ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Critical Role ◽  
Serum Levels ◽  
Alveolar Epithelial Cells ◽  
M1 Macrophages ◽  
Monocyte Chemoattractant Protein 1 ◽  
Alveolar Epithelial ◽  
M1 Macrophage ◽  
Tnf Α

The goal of the present study was to investigate the role of M1 macrophages in acute lung injury (ALI). To address this, we used lipopolysaccharide (LPS)-treated wild-type and CD11b-DTR mice, and examined their M1 macrophage levels, and the extent of their inflammation and pulmonary injuries. In addition, we evaluated pulmonary function by measuring the expressions of SP-A and SP-B in infiltrated M1 macrophages. Finally, we co-cultured the mouse type II-like alveolar epithelial cells (AT-II) and mouse pulmonary microvascular endothelial cells (PMECs) with M1 macrophages in the presence of TNF-α or H2O2 and assessed them for viability and apoptosis. After LPS treatment, we observed that the number of pulmonary M1/M2 macrophages and the serum levels of interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and reactive oxygen species (ROS) significantly increased. Furthermore, the increase in cytokines was accompanied with the initiation of lung injury indicated by the decreased levels of SP-A and SP-B. In macrophage-depleted CD11b-DTR mice, ALI was attenuated, serum levels of IL-1β, TNF-α and ROS were reduced, and lung levels of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) were decreased. After administering TNF-α and H2O2, the proapoptotic effect of M1 macrophages on AT-II or PMECs significantly increased, the cell viabilities significantly decreased, and apoptosis significantly increased. Our results suggest that M1 macrophages are recruited to the lungs where they significantly contribute to an increase in TNF-α and ROS production, thus initiating ALI.

Sign in / Sign up

Export Citation Format

Share Document