• The Korean Journal of Physiology and Pharmacology
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• v.4 no.3
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• pp.219-226
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• 2000

In order to elucidate the role of platelet activating factor (PAF) in the acute lung injury induced by endotoxin (ETX), activities of phospholipase A2, lyso PAF acetyltransferase and oxidative stress by neutrophilic respiratory burst were probed in the present study. To induce acute lung injury, $100\;{\mu}g$ of E.coli ETX (type 0127; B8) was instilled directly into the tracheae of Sprague-Dawley rats. Five hours after the ETX instillation, induction of acute lung injury was confirmed by lung leak index and protein contents in the bronchoalveolar lavage (BAL) fluid. At the same time, lung phospholipase A2 (PLA2) activity and expression of group I and II secretory type PLA2 were examined. In these acutely injured rats, ketotifen fumarate, known as lyso PAF acetyltransferase inhibitor and mepacrine were administered to examine the role of PAF in the pathogenesis of the acute lung injury. To know the effect of the ETX in the synthesis of the PAF in the lungs, lyso PAF acetyltransferase activity and PAF content in the lungs were measured after treatments of ETX, ketotifen fumarate and mepacrine. In addition, the role of neutrophils causing the oxidative stress after ETX was examined by measuring lung myeloperoxidase (MPO) and enumerating neutrophils in the BAL fluid. To confirm the oxidative stress in the lungs, pulmonary contents of malondialdehyde (MDA) were measured. After instillation of the ETX in the lungs, lung leak index increased dramatically (p＜0.001), whereas mepacrine and ketotifen decreased the lung leak index significantly (p＜0.001). Lung PLA2 activity also increased (p＜0.001) after ETX treatment compared with control, which was reversed by mepacrine and ketotifen (p＜0.001). In the examination of expression of group I and II secretory PLA2, mRNA synthesis of the group II PLA2 was enhanced by ETX treatment, whereas ketotifen and WEB 2086, the PAF receptor antagonist, decreased the expression. The activity of the lysoPAF acetyltransferase increased (p＜0.001) after treatment of ETX, which implies the increased synthesis of PAF by the remodelling of lysoPAF in the lungs. Consequently, the contents of the PAF in the lungs were increased by ETX compared with control (p＜0.001), while mepacrine (p＜0.001) and ketotifen (p＜0.01) decreased the synthesis of the PAF in the lungs of ETX treated rats. The infiltration of the neutrophils was confirmed by measuring and enumerating lung MPO and the neutrophils in the BAL fluid respectively. Compared with control, ETX increased lung MPO and number of neutrophils in BAL significantly (p＜0.001) whereas mepacrine and ketotifen decrerased number of neutrophils (p＜0.001) and MPO (p＜0.05, p＜0.001, respectively). The lung MDA contents were also increased (p＜0.001) by ETX treatment, but treatment with mepacrine (p＜0.001) and ketotifen (p＜0.01) decreased the lung MDA contents. Collectively, we conclude that ETX increases PLA2 activity, and that the subsequently increased production of PAF was ensued by the remodelling of the lyso PAF resulting in tissue injury by means of oxidative stress in the lungs.

• Animal Bioscience
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• v.36 no.8
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• pp.1221-1227
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• 2023

Objective: The present study aimed to investigate the effect of dietary lutein on egg production, follicles, reproductive hormones, fertility, hatchability, and oxidative injury indexes of hens. Methods: Treatments consisted of a control diet (CON) and three lutein-supplementing diets at 25 (L1), 50 (L2), or 75 (L3) mg/kg of diet. Egg production was measured using 576 Arbor Acres breeder hens at 61 to 65 wk and follicles grades, reproductive hormones, fertility, hatchability, tissue lutein contents, and oxidative injury indexes were determined at 65 wk. Results: The results showed that at 65 wk, lutein- supplementing diets increased (p<0.05) egg production, follicular grades, fertility, hatchability, estradiol (E2), luteinizing hormone, progesterone (PROG), lutein content in the serum and yolk, compared to CON. L2 and L3 showed more pronounced (p<0.05) effects on egg production, PROG, and yolk lutein content than L1. With the increase of lutein doses from 25 to 75 mg/kg, there were linear increases (p<0.05) in egg production, lutein content, and PROG, and a quadratic trend (p<0.05) in E2. For the oxidative injury products, lutein-supplementing diets decreased (p<0.05) malondialdehyde (MDA) and protein carbonyl (PCO) in the serum, MDA and 8-hydroxy 2 deoxyguanosine (8-OHdG) in the yolk. There were linear decreases (p<0.05) in 8-OHdG in the serum, MDA, PCO, and 8-OHdG in the yolk, a quadratic trend (p<0.05) on serum 8-OHdG. Conclusion: It is concluded that lutein supplementation can improve egg production and fertility by beneficially regulating reproductive hormones and oxidative status in aged hens.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.479-491
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• 1998

In order to know the pathogenesis of adult respiratory distress syndrome (ARDS) in association with the oxidative stress by neutrophils, the role of platelet activating factor (1-0-alkyl-2-acetyl-snglycero-3-phosphocholine, PAF) was investigated during acute lung injury induced by interleukin- $1{\alpha}$ (IL-1) in rats. An insufflation of IL-1 into the rat's trachea increased the acetyltransferase activity in the lung and the increase of PAF content was followed. As evidences of acute lung injury by neutrophilic respiratory burst, lung leak index, myeloperoxidase activity, numbers of neutrophils in the bronchoalveolar lavage fluid, neutrophilic adhesions to endothelial cells and NBT positive neutrophils were increased after IL-1 treatment. In addition, a direct instillation of PAF into the trachea caused acute lung leak and the experimental results showed a similar pattern in comparison with IL-1 induced acute lung injury. For the confirmation of oxidative stress during acute lung leak by IL-1 and PAF, a histochemical electron microscopy was performed. In IL-1 and PAF treated lungs of rats, the deposits of cerrous perhydroxide were found. To elucidate the role of PAF, an intravenous injection of PAF receptor antagonist, WEB 2086 was given immediately after IL-1 or PAF treatment. WEB 2086 decreased the production of hydrogen peroxide and the acute lung leak. In ultrastructural study, WEB 2086 mitigated the pathological changes induced by IL-1 or PAF. The nuclear factor kappa B (NFkB) was activated by PAF and this activation was inhibited by WEB 2086 almost completely. Based on these experimental results, it is suggested that the PAF produced in response to IL-1 through the remodeling pathway has the major role for acute lung injury by neutrophilic respiratory burst. In an additional experiment, we can also come to conclude that the activation of the NFkB by PAF is thought to be the fundamental mechanism to initiate the oxidative stress by neutrophils causing release of proinflammatory cytokines and activation of phospholipase $A_2$.

• Biomedical Science Letters
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• v.7 no.3
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• pp.99-102
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• 2001

Toluene is mainly metabolized in liver by oxidative pathway. Oxigen free radicals occur through the process of toluene metabolism Therefore it causes tissue and cell min by the oxygen free radicals from the metabolism of toluene. Melatonin acts as a highly efficient free radical scavenger that protects cells from damage by oxygen free radicals. To test this hypothesis, toluene hepatotoxicity was induced by an abdominal injection of toluene. To see if the melatonin protects the rat's liver, melatonin was administrated orally, at the time of each toluene injection. Aspartate aminotransferase(AST), alanin aminotransferase(ALT), latic dehydrogenase(LDH) and alkaline phosphatase(ALP) levels in serum were measured to estimate hepatic function. Malondialdehyde(MDA), which gives an indirect index of oxidative injury was also measured. Hippuric acid is the last metabolic Production of toluene was measured by HPLC. There were significantly higher in AST, ALT, LDH, MDA and hippuric acid in toluene group, but there were no significant difference in melatonin group except ALT and hippuric acid. There was significantly lower in ALP level in toluene group, but there was no significant difference melatonin group, suggesting a significant hepatotoxicity due to oxygen free radicals through the process of toluene metabolism Melatonin treatment significantly protected hepatic function and free radical-mediated injury in the liver against toluene-induced changes. Accordingly, this study shows that melatonin is helpful in protecting liver injury by acute toluene intoxication.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.4
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• pp.405-414
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• 1999

The role of platelet-activating factor (PAF) was investigated in intestinal ischemia/reperfusion (I/R) induced acute lung injury associated with oxidative stress. To induce acute lung injury following intestinal I/R, superior mesenteric arteries were clamped with bulldog clamp for 60 min prior to the 120 min reperfusion in Sprague-Dawley rats. Acute lung injury by intestinal I/R was confirmed by the measurement of lung leak index and protein content in bronchoalveolar lavage (BAL) fluid. Lung leak and protein content in BAL fluid were increased after intestinal I/R, but decreased by WEB 2086, the PAF receptor antagonist. Furthermore, the pulmonary accumulation of neutrophils was evaluated by the measurement of lung myeloperoxidase (MPO) activity and the number of neutrophils in the BAL fluid. Lung MPO activity and the number of neutrophils were increased (p＜0.001) by intestinal I/R and decreased by WEB 2086 significantly. To confirm the oxidative stress induced by neutrophilic respiratory burst, gamma glutamyl transferase (GGT) activity was measured. Lung GGT activity was significantly elevated after intestinal I/R (p<0.001) but decreased to the control level by WEB 2086. On the basis of these experimental results, phospholipase $A_2\;(PLA_2),$ lysoPAF acetyltransferase activity and PAF contents were measured to verify whether PAF is the causative humoral factor to cause neutrophilic chemotaxis and oxidative stress in the lung following intestinal I/R. Intestinal I/R greatly elevated $PLA_2$ activity in the lung as well as intestine (p<0.001), whereas WEB 2086 decreased $PLA_2$ activity significantly (p<0.001) in both organs. LysoPAF acetyltransferase activity, the PAF remodelling enzyme, in the lung and intestine was increased significantly (p<0.05) also by intestinal I/R. Accordingly, the productions of PAF in the lung and intestine were increased (p<0.001) after intestinal I/R compared with sham rats. The level of PAF in plasma was also increased (p<0.05) following intestinal I/R. In cytochemical electron microscopy, the generation of hydrogen peroxide was increased after intestinal I/R in the lung and intestine, but decreased by treatment of WEB 2086 in the lung as well as intestine. Collectively, these experimental results indicate that PAF is the humoral mediator to cause acute inflammatory lung injury induced by intestinal I/R.

• Biomedical Science Letters
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• v.9 no.1
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• pp.37-42
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• 2003

The present study was conducted to determine whether administration of heat extract of Lepidii Semen has an inhibitory effect on neutrophil-derived oxidative injury following dermal scald burn in rats. Acute lung injury was induced by scald burn (15% of TBSA) in rats. To identify acute edematous lung injury, protein concentrations and numbers of polymorphonuclear leukocytes were measured in bronchoalveolar lavage (BAL) at 5 h after skin burn. In addition, the level of lung KC (neutrophil chemoattractant cytokine) and activity of lung myeloperoxidase (MPO) were measured, and histopathological changes were observed as well. Lung weight and concentration of BAL protein, the index of lung injury, were clearly increased at 5 h postburn compared with those of sham-operated group. Administration of heat extract of Lepidii Semen after scald burn inhibited the production of KC in lung tissue and decreased the activity of lung MPO related to infiltration of neutrophils. In histopathological changes in lung tissue, infiltration of inflammatory cells and pulmonary edema induced by skin burn were decreased by administration of heat extract of Lepidii Semen after scald burn. These results suggest that Lepidii Semen may be an effective medical stuff for acute lung injury induced by skin burn.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.169-173
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• 2013

Renal ischemia-reperfusion (IR) causes remote liver damage. Oxytocin has anti-inflammatory and antioxidant effects. The main purpose of this study was to evaluate the protective function of oxytocin (OT) in remote liver damage triggered by renal IR in rats. Twenty four rats were randomly divided into four different groups, each containing 8 rats. The groups were as follows: (1) Sham operated group; (2) Sham operated+OT group (3) Renal IR group; (4) Renal IR+OT group. OT ($500{\mu}g/kg$) was administered subcutaneously 12 and 24 hours before and immediately after ischemia. At the end of experimental procedure, the rats were sacrificed, and liver specimens were taken for histological assessment or determination of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), paraoxonase (PON-1) activity and nitric oxide (NO). The results showed that renal IR injury constituted a notable elevation in MDA, TOS, Oxidative stress index (OSI) and significantly decreased TAS, PON-1 actvity and NO in liver tissue (p<0.05). Additionally renal IR provoked significant augmentation in hepatic microscopic damage scores. However, alterations in these biochemical and histopathological indices due to IR injury were attenuated by OT treatment (p<0.05). These findings show that OT ameliorates remote liver damage triggered by renal ischemia-reperfusion and this preservation involves suppression of inflammation and regulation of oxidant-antioxidant status.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.233-239
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• 2017

Background: Nephrotoxicity is the major side effect in cisplatin chemotherapy. Previously, we reported that the ginsenosides Rk3 and Rh4 reduced cisplatin toxicity on porcine renal proximal epithelial tubular cells (LLC-PK1). Here, we aimed to evaluate the protective effect of ginsenosides Rk3 and Rh4 on kidney function and elucidate their antioxidant effect using in vitro and in vivo models of cisplatin-induced acute renal failure. Methods: An enriched mixture of ginsenosides Rk3 and Rh4 (KG-KH; 49.3% and 43.1%, respectively) was purified from sun ginseng (heat processed Panax ginseng). Cytotoxicity was induced by treatment of $20{\mu}M$ cisplatin to LLC-PK1 cells and rat model of acute renal failure was generated by single intraperitoneal injection of 5 mg/kg cisplatin. Protective effects were assessed by determining cell viability, reactive oxygen species generation, blood urea nitrogen, serum creatinine, antioxidant enzyme activity, and histopathological examination. Results: The in vitro assay demonstrated that KG-KH ($50{\mu}g/mL$) significantly increased cell viability (4.6-fold), superoxide dismutase activity (2.8-fold), and glutathione reductase activity (1.5-fold), but reduced reactive oxygen species generation (56%) compared to cisplatin control cells. KG-KH (6 mg/kg, per os) also significantly inhibited renal edema (87% kidney index) and dysfunction (71.4% blood urea nitrogen, 67.4% creatinine) compared to cisplatin control rats. Of note, KG-KH significantly recovered the kidney levels of catalase (1.2-fold) and superoxide dismutase (1.5-fold). Conclusion: Considering the oxidative injury as an early trigger of cisplatin nephrotoxicity, our findings suggest that ginsenosides Rk3 and Rh4 protect the kidney from cisplatin-induced oxidative injury and help to recover renal function by restoring intrinsic antioxidant defenses.

• Tuberculosis and Respiratory Diseases
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• v.70 no.6
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• pp.482-489
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• 2011

Background: Based on the assertion that apocynin diminishes acute lung injury (ALI) by inhibition of NADPH oxidase, the effect of apocynin was tested in interleukin-$1{\alpha}$ (IL-1)-induced ALI in rats. Methods: IL-1 was insufflated into the trachea of Sprague-Dawley rats to induce ALI, and apocynin (8 mg/kg) was given intravenously for inhibition of NADPH oxidase. In addition, we determined whether apocynin inhibited generation of superoxide anions from isolated human neutrophils. Five hours after IL-1 instillation, lung injury parameters, expression of cytosolic phospholipase A2 (cPLA2) by cells from bronchoalveolar lavage (BAL), an index of oxidative stress in lung tissues (${\gamma}$-glutamyltranspeptidase, activity), and ultrastructure of alveolar type II (AT II) cells were evaluated. Results: Apocynin decreased the generation of free radicals from phorbol myristate (PMA)-activated neutrophils in vitro, but did not ameliorate ALI. IL-1 induced enhancement of the expression of cPLA2 on neutrophils was not altered by apocynin. Conclusion: Apocynin induced suppression of the generation of superoxide anions from neutrophils by inhibition of NADPH oxidase does not attenuate IL-1-induced ALI in rats.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.263-273
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• 1999

The role of phospholipase $A_2\;(PLA_2)$ in acute lung leak induced by intestinal ischemia was investigated in association with neutrophilic respiratory burst. To induce lung leak, we generated intestinal ischemia for 60 min prior to the 120 min reperfusion by clamping superior mesenteric artery in Sprague-Dawley rats. Acute lung leak was confirmed by the increased lung leak index and protein content in bronchoalveolar fluid. These changes were inhibited by mepacrine, the non-specific $PLA_2$ inhibitor. The lung myeloperoxidase (MPO) activity denoting the pulmonary recruitment of neutrophils was increased by intestinal I/R, but decreased by mepacrine. Simultaneously, the number of leukocytes in bronchoalveolar fluid was increased by intestinal ischemia/reperfusion (I/R) and decreased by mepacrine. Gamma glutamyl transferase activity, an index of oxidative stress in the lung, was increased after intestinal I/R but decreased by mepacrine, which implicates that $PLA_2$ increases oxidative stress caused by intestinal I/R. The $PLA_2$ activity was increased after intestinal I/R not only in the intestine but also in the lung. These changes were diminished by mepacrine. In the cytochemical electron microscopy to detect hydrogen peroxide, intestinal I/R increased the generation of the hydrogen peroxide in the lung as well as in the intestine. Expression of interleukin-1 (IL-1) in the lung was investigated through RT-PCR. The expression of IL-1 after intestinal I/R was enhanced, and again, the inhibition of $PLA_2$ suppressed the expression of IL-1 in the lung. Taken together, intestinal I/R seems to induce acute lung leak through the activation of $PLA_2$, the increase of IL-1 expression associated with increased oxidative stress by neutrophilic respiratory burst.