• BMB Reports
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• v.56 no.2
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• pp.96-101
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• 2023

Particulate matter is an air pollutant composed of various components, and has adverse effects on the human body. Particulate matter is known to induce cell death by generating an imbalance in the antioxidant system; however, the underlying mechanism has not been elucidated. In the present study, we demonstrated the cytotoxic effects of the size and composition of particulate matter on small intestine cells. We found that particulate matter 2.5 (PM_2.5) with extraction ion (EI) components (PM_2.5 EI), is more cytotoxic than PM containing only polycyclic aromatic hydrocarbons (PAHs). Additionally, PM-induced cell death is characteristic of ferroptosis, and includes iron accumulation, lipid peroxidation, and reactive oxygen species (ROS) generation. Furthermore, ferroptosis inhibitor as liproxstatin-1 and iron-chelator as deferiprone attenuated cell mortality, lipid peroxidation, iron accumulation, and ROS production after PM_2.5 EI treatment in human small intestinal cells. These results suggest that PM_2.5 EI may increase ferroptotic-cell death by iron accumulation and ROS generation, and offer a potential therapeutic clue for inflammatory bowel diseases in human small intestinal cells.

• Archives of Pharmacal Research
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• v.27 no.11
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• pp.1147-1153
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• 2004

Bladder cancer is a common cancer with high risk of recurrence and mortality. Intravesicle chemotherapy after trans-urethral resection is required to prevent tumor recurrence and progression. It has been known that antioxidants enhance the antitumor effect of bacillus Calmette-Guerin (BCG), the most effective intravesical bladder cancer treatment. Capsaicin, the major pungent ingredient in genus Capsicum, has recently been tried as an intravesical drug for overactive bladder and it has also been shown to induce apoptotic cell death in many cancer cells. In this study, we investigated the apoptosis-inducing effect and alterations in the cellular redox state of capsaicin in MBT-2 murine bladder tumor cells. Capsaicin induced apoptotic MBT-2 cell death in a time- and dose-dependent manner. The capsaicin-induced apoptosis was blocked by the pretreatment with Z-VAD-fmk, a broad-range caspase inhibitor, or Ac-DEVD-CHO, a caspase-3 inhibitor. In addition to the caspase-3 activation, capsaicin also induced cytochrome c release and decrease in Bcl-2 protein expression with no changes in the level of Bax. Furthermore, capsaicin at the concentration of inducing apoptosis also markedly reduced the level of reactive oxygen species and lipid peroxidation, implying that capsaicin may enhance the antitumor effect of BCG in bladder cancer treatment. These results further suggest that capsaicin may be a valuable intravesical chemotherapeutic agent for bladder cancers.

• Journal of Food Hygiene and Safety
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• v.1 no.2
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• pp.143-149
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• 1986

Paraquat의 만성독성에 대한 vitamin E 급여의 효과를 조사하기 위하여 랫드에 paraquat를 50 ppm의 농도로 희석한 물을 음수 대신 투여하면서 vitamin E 함유 사료를 급여하여 paraquat에 대한 vitamin E의 방어 효과를 측정하였는 바 다음과 같은 결과를 얻었다. 1.혈장 vitamin E 농도는 사료 kg 당 10 mg까지의 vitamin E 함유 사료의 급여로 약 150$\mu\textrm{g}$/100ml까지 급격히 상승하였으며 그 후 급여량의 증가에도 비교적 안정된 혈중 농도를 유지하였고, 또한 paraquat 투여는 vitamin E 급여량에 관계없이 혈중 vitamin E 농도의 감소를 가져왔다. 2. 간저장 vitamin E 농도는 혈장 vitamin E 농도와 달리 급여량의 증가에 따라 비례하여 증가하는 경향을 보였으며 paraquat 투여에 의한 영향이 적었다. 3. Paraquat 투여는 적혈구 용혈율을 크게 증가시켰음 (95%), 100$\mu\textrm{g}$/100ml 이상의 vitamin E 혈장 농도에서는 안정된 적혈구 용혈율 (10% 이하)을 나타내었다. 4. Paraquat 투여는 혈장 trypsin inhibitor capacity를 크게 증가시켰으며, vitamin E 급여에 의하여 다소 회복되는 경향을 보였으나 정상에 이르지 못하였다. 5. 혈장 및 적혈구 glutathione peroxidase 활성은 paraquat 투여에 의하여 영향을 받지 않았다. 6. paraquat 투여 후의 lipid peroxide는 vitamin E의 급여로 감소되었다.

• Archives of Pharmacal Research
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• v.18 no.3
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• pp.189-194
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• 1995

The focus of this study was to investigate the influences of enzymatic scavengers of active oxygen metabolites and phospholipase $A_2$ inhibitor on hepatic secretory and microsomal function during hepatic ischemia/reperfusion. Rats were pretreated with free radical scavengers such as superoxide dismutase (SOD), catalase, deferoxamine and phospholipase $A_2$ inhibitor such as quinacrine and then subjected to 60 min. no-flow hepatic ischemia in vivo. After 1, 5 hr of reperfusion, bile was collected, blood was obtained from the abdominal aorta, and liver microsomes were isolated. Serum aminotransferase (ALT) level was increased at 1 hr and peaked at 5 hr. The increase in ALT was significantly attenuated by SOD plus catalase, deferoxamine and quinacrine especially at 5 hr of reperfusion. The wet weight-to-dry weight ratio of the liver was significantly increased by ischemia/reperfusion. SOD and catalase treatment minimized the increase in this ratio. Hepatic lipid peroxidiltion was elevated by ischemia/reperfusion, and this elevation was inhibited by free radical scavengers and quina crine. Bile flow and cholate output, but not bilirubin output, were markedly decreased by ischemia/reperfusion and quinacrine restored the secretion. Cytochrome $P_{450}$ content was decreased by ischemia/reperfusion and restored by free radical scavengers and quinacrine to the level of that of the sham operated group. Aminopyrine N-demethylase activity was decreased and aniline p-hydroxylase was increased by ischemia/reperfusion. The changes in the activities of the two enzymes were prevented by free radical scavengers and quinacrine. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory functions as well as microsomal drug metabolizing systems by increasing lipid peroxidation, and in addition to free radicals, other factors such as phospholipase $A_2$ are involved in pathogenes of hepatic dysfunction after ischemia/reperfusion.

• Journal of Chest Surgery
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• v.21 no.5
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• pp.803-815
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• 1988

The present experiments were performed to confirm the hypothesis that xanthine oxidase[XOD], as a source and mechanism of oxygen radical production, plays an important role in the genesis of the reperfusion injury of ischemic myocardium. The experimental ischemic-reperfusion injury was induced in isolated, Langendorff preparations of rat hearts by 60 min. Of global ischemia with aortic clamping followed by 20 min. of reperfusion with oxygenated Krebs-Henseleit solution[pH 7.4, 37*C]. The results were as follows: 1. The releases of creatine phosphokinase and a lipid peroxidation product, malondialdehyde[MDA] into the coronary effluent were abruptly increased upon reperfusion of ischemic hearts. The increases of the enzyme and MDA were suppressed significantly in the hearts removed from rats pretreated with allopurinol, a specific XOD inhibitor[20mg/kg, oral, 24 hrs and 2 hrs before study]. This effect of allopurinol was comparable to that of oxygen radical scavengers, superoxide dismutase[5, 000U] and catalase[12, 500 U]. 2. The increased SOD-inhibitable reduction of ferricytochrome C, which was infused to the hearts starting with reperfusion, was significantly suppressed in allopurinol pretreated hearts. 3. Activities of myocardial XOD were compared in the normal control hearts and the ischemic ones. Total enzyme activities were not different in both hearts. However, comparing with the control, the ischemic ones showed higher activity in 0-form and lower activities in D-form and D/O-form. 4. In the ischemic hearts, phenylmethylsulfonyl fluoride, a serine protease inhibitor, prevented significantly the increase of 0-form and the decreases of D and D/O-form, while thiol reagents did not affect the changes of the enzyme. 5. The increase of 0-form and the decreases of D and D/0-form were not significant in both calcium-free perfused and pimozide, a calmodulin inhibitor, treated ischemic hearts. 6. The SOD-inhibitable reduction of ferricytochrome C were suppressed by PMSF and pimozide treatment as well as by calcium-free perfusion. It is suggested from these results that in the ischemic rat myocardium, xanthine oxidase is converted to oxygen radical producing 0-form by calcium, calmodulin-dependent proteolysis and plays a contributing role in the genesis of ischemic-reperfusion injury by producing oxygen free radicals.

• The Journal of Korean Medicine
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• v.32 no.1
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• pp.109-120
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• 2011

Objectives: The aim of this investigation was to evaluate the efficacy of KHchunggan-tang aqueous extract on the experimental nonalcoholic fatty liver disease(NAFLD) induced by palmitate. Materials and Methods: To generate a cellular model of NAFLD, we used HepG2 cells, a human hepatoma cell line, treated with 0.5 mM palmitate. By this cellular model, effects of KHchunggan-tang aqueous extract were evaluated. Intracellular lipid accumulation, free radical formation, and apoptosis were detected by Nile red staining, 2',7'-dichloroflourescin diacetate(H2DCF-DA), and 4',6-diamidino-2-phenylindole(DAPI)/propidium iodide(PI) staining, respectively. Some proteins related with NAFLD were determined by western blot. Results: Typical pathological features of NAFLD occurred in the cellular model. Palmitate increased the levels of intracellular lipid vacuoles, decreased cell viability, and increased apoptosis. Palmitate increased free radical formation and lipid peroxidation, too. However, KHchunggan-tang aqueous extract reduced palmitate-induced pathologic features, i.e. steatosis, free radical formation, and apoptosis. In addition, KHchunggan-tang aqueous extract suppressed palmitate-activated c-Jun N-terminal kinase(JNK) signaling, and SP600125, a JNK inhibitor, significantly reversed the palmitate-induced pathologic changes as KHchunggan-tang aqueous extract. It means that the signaling pathway other than JNK can be involved in the KHchunggan-tang mediated cellular protection of palmitate-treated Hep G2 cells. Conclusions: These results suggest that KHchunggan-tang aqueous extract has hepatoprotective effects on NAFLD with combined properties in cellular steatosis, ROS production, and cytoprotection, and thus may have valuable clinical applications for treatment of this chronic liver disease.

• Biomolecules & Therapeutics
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• v.18 no.3
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• pp.300-307
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• 2010

Photosensitized peroxidation of membrane lipids has been implicated in skin pathologies such as phototoxicity and premature aging. We have previously reported that syriacusin compounds isolated from Hibiscus Syriacus inhibited lipid peroxidation. Here, we investigated whether syriacusins could be effective inhibitor to skin aging using ultraviolet-irradiated human dermal fibroblast cells (HDFCs). Syriacusins A, B, and C inhibit the activity of human neutrophil elastase (HNE), a serine protease to degrade extracellular matrix (ECM) proteins including elastin, with $IC_{50}s$ of 8.0, 5.2, and $6.1\;{\mu}M$, respectively. No changes in cell viability were detected by syriacusins A and B in UV-B ($10\;mJ/cm^2$) irradiated HDFCs. Matrix metallo-proteinase (MMP)-1 expression in HDFCs was increased by UV-B irradiation. MMP-1 expression in UV-B irradiated HDFCs was decreased by $10\;{\mu}M$ and $20\;{\mu}M$ syriacusin A to 50% and 20% of untreated control, respectively. Syriacusin B treated with $20\;{\mu}M$ reduced MMP-1 expression in UV-B irradiated HDFCs to 60% of untreated control. Syriacusin A also inhibited MMP-2 expression accompanying the increase of type-I pro-collagen in UV-B irradiated HDFCs. These results demonstrate that syriacusin A could be a more effective compound to inhibit skin aging caused by UV irradiation. It suggests that syriacusins A and B might be developed as possible agents to treat or prevent skin aging.

• BMB Reports
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• v.45 no.8
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• pp.482-487
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• 2012

To identify the novel inhibitors of endoplasmic reticulum stress-induced cell death, we performed a high throughput assay with a chemical library containing a total of 3,280 bioactive small molecules. Cyclosporine A and bromocriptine were identified as potent inhibitors of thapsigargiin-induced cell death (cut-off at $4{\sigma}$ standard score). However, U74389G, the potent inhibitor of lipid peroxidation had lower activity in inhibiting cell death. The inhibition effect of cyclosporine A and bromocriptine was specific for only thapsigargin-induced cell death. The mechanism of inhibition by these compounds was identified as modification of the expression of glucose regulated protein-78 (GRP-78/Bip) and inhibition of phosphorylation of p38 mitogen activated protein kinase (MAPK). However, these compounds did not inhibit the same events triggered by tunicamycin, which was in agreement with the cell survival data. We suggest that the induction of protective unfolded protein response by these compounds confers resistance to cell death. In summary, we identified compounds that may provide insights on cell death mechanisms stimulated by ER stress.

• The Journal of Korean Medicine
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• v.36 no.4
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• pp.42-55
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• 2015

Purpose: The object of this study is to observe the anti-ulcerative effects of BK-1202 (IGM), a mixed herbal formula consisting of 9 herbal drugs, which have been traditional Korean medicine for treating various digestive diseases, on indomethacin-induced gastric ulcer in rat. Methods: Three different doses of IGM extract (200, 100 and 50 mg/kg) were orally administered once 30 min before indomethacin treatment. Six hours after indomethacin treatment, changes in the gross lesion scores, fundic histopathology, MPO activity and antioxidant activities were observed. The results were compared with two reference groups treated with omeprazole (10 mg/kg), antioxidant and proton pump inhibitor, and DA-9601 (100 mg/kg), a standardized extract of the herb Artemisiaasiatica. Results: In all three doses of IGM extract, significantly decreased gastric damages were observed in the indomethacin-induced gastric ulcer rats, when compared with the indomethacin-treated control rats. IGM extracts also strengthened the antioxidative defense systems, decreasing the level of lipid peroxidation and catalase activity while increasing the superoxide dismutase and glutathione contents. IGM extracts showed similar anti-ulcerative effects to those shown by equal dose of DA-9601, and the effects of 50 mg/kg IGM extracts were comparable to those of 10 mg/kg omeprazole. Conclusion: The results obtained in this study suggest that IGM extract has favorable effects on the indomethacin -induced gastric damages by strengthening the antioxidative defense systems and enhancing anti-inflammatory effects.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.20 no.1
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• pp.1-13
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• 1994

An antioxidative compound was isolated from pine needles. This compound was identified as 4-hydroxy-5-methyl-3[2H]-furanone on the basis of spectroscopic evidences. It scavenged 1,1-diphenyl-2-picrylhydrazyl free radicals more efficiently than maltol and tocopherol did. It exhibited an inhibitory effect on the lipid peroxidation of rat liver microsome induced by Fe(ll)/ascorbate, and the protective effect against UV cytotoxicity in cultured human fibroblasts. In addition, HMF appeared to prevent the cellular melanogenesis in the cultured murine melanoma cells, more effectively than kojic acid, a well known inhibitor of melanogenesis, while the former was not so effective as the latter for the inhibilion of the tyrosinase. Considering that cellular melanogenesis is a metabolic process triggered by oxidative stress, it was tentatively deduced that the antioxidative property of HMF may afford the effect against cellular pigmentation by alleviating the causative stress. This study provided a novel inhibitor of melanogenesis, that might be useful for the cosmetic applications.