• Archives of Pharmacal Research
• /
• 제28권3호
• /
• pp.311-318
• /
• 2005

Oxidative stress has been reported to elevate ceramide level during cell death. The purpose of the present study was to modulate cell death in relation to cellular glutathione (GSH) level and GST (glutathione S-transferase) expression by regulating the sphingolipid metabolism. LLC­PK1 cells were treated with H$_2$O$_2$ in the absence of serum to induce cell death. Subsequent to exposure to H$_2$O$_2$, LLC-PK1 cells were treated with desipramine, sphingomyelinase inhibitor, and N-acetylcysteine (NAC), GSH substrate. Based on comparative visual observation with H202-treated control cells, it was observed that 0.5 $\mu$M of desipramine and 25 $\mu$M of NAC exhibited about 90 and $95\%$ of cytoprotection, respectively, against H$_2$O$_2$-induced cell death. Desipramine and NAC lowered the release of LDH activity by 36 and $3\%$ respectively, when compared to $71\%$ in H$_2$O$_2$-exposed cells. Cellular glutathione level in 500 $\mu$M H202-treated cells was reduced to 890 pmol as compared to control level of 1198 pmol per mg protein. GST P1-1 expression was decreased in H$_2$O$_2$-treated cells compared to healthy normal cells. In conclusion, it has been inferred that H$_2$O$_2$-induced cell death is closely related to cellular GSH level and GST P1-1 expression in LLC-PK1 cells and occurs via ceramide elevation by sphingomyelinase activation.

• Food Science and Biotechnology
• /
• 제16권6호
• /
• pp.967-974
• /
• 2007

The present work is aimed to evaluate the protective effect of glutathione-enriched Saccharomyces cerevisiae FF-8 strain on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity and oxidative stress in rats. The activities of liver markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase), lipid peroxidative index (thiobarbituric acid-reactive substances), and the antioxidant status (reduced glutathione) were used to monitor those protective roles of FF-8 strain. The liver marker enzymes in plasma and the lipid peroxidation in the liver were increased when $CCl_4$ was treated but these were significantly decreased by FF-8 strain treatment. The hepatic concentration of glutathione in the current glutathione-enriched FF-8 strain fed animal was approximately twice as high as the normal, but this was slightly increased in response to $CCl_4$ plus glutathione-enriched FF-8 strain. The increased liver triglyceride concentration due to the $CCl_4$ treatment was significantly decreased by FF-8 strain and the reduced level reached to that of normal group. Administration of FF-8 strain in normal rat did not show any signs of harmful effects. Therefore, the current findings suggest that FF-8 strain could be an effective antioxidant with no or negligible side-effects and it might be useful for the purpose of protection treatment of hepatotoxicity and oxidative stress in $CCl_4$-treatment in rat.

• Biomolecules & Therapeutics
• /
• 제13권4호
• /
• pp.256-262
• /
• 2005

We examined the signaling molecules involved in the 6-hydroxydopamine (6-OHDA)-induced neuronal cell death and increase in cellular glutathione (GSH) level in SK-N-SH cells. The 6-OH-DA-induced cell death was significantly prevented by the pretreatment with N-acetylcysteine (NAC), a thiol antioxidant, and BAPTA, an intracellular $Ca^{2+}$ chelator. Although 6-OHDA induced ERK phosphorylation, the pretreatment with PD98059, an ERK inhibitor, did not block 6-OHDA-induced cell death. In addition, the 6-OHDA-induced activation of caspase-3, a key signal for apoptosis, was blocked by the pretreatment with NAC and BAPTA. While the level of reactive oxygen species (ROS) was significantly increased in the 6-OHDA-treated cells, the cellular GSH level was not altered for the first 6-hr exposure to 6-OHDA, but after then, the level was significantly increased, which was also blocked by the pretreatment with NAC and BAPTA, but not by PD98059. Depletion of GSH by pretreating the cells with DL-buthionine-(S,R)-sulfoximine (BSO), a glutathione synthesis inhibitor, rather significantly potentiated the 6-OHDA-induced death. In contrast to the pretreatment with NAC, 6-OHDA-induced cell death was not prevented by the post-treatment with NAC 30 min after 6-OHDA treatment. The results indicate that the GSH level which is increased adaptively by the 6-OHDA-induced ROS and intracellular $Ca^{2+}$ is not enough to overcome the death signal mediated through ROS-$Ca^{2+}$ -caspase pathway.

• Journal of Nutrition and Health
• /
• 제20권2호
• /
• pp.111-121
• /
• 1987

어유를 섭취하였을 때, 체내 과산화물 생성과 항산화 기능을 조사하며, 그 결과를 다른 식이지방과 비교하기 위하여, 고등어유, 대두유, 쇠기름, 들기름, 채종유의 5 종의 지방을 먹이의 10% 되게 식이를 조제하여 70g 내외의 암, 수컷의 흰쥐에게 섭취시켰다. 출생후 초기 성장시에 적응도를 관찰하기 위하여, 위의 쥐들을 34일간 조제식이로 사육한후, 교배시켜 출생한 2 대째 쥐들을 수유시기(17일, 26일)과 이유시기(39일)에 희생시키고, 출산, 수유를 마친 어미쥐(나이 123일, 총 식이일수 81일)를 희생하여 간과 뇌조직의 지질과산화물, $\alpha$-tocopherol, glutathione 양을 정량하고, glutathione peroxidase, superoxide dismutase의 활성을 측정하였다. 간조직의 지질과산화물 값은 고등어유를 섭취한 어미쥐와 수유기(17, 26일)의 새끼쥐들에게서 타군에 비해 높았으나 39일의 새끼쥐에서는 채종유보다는 높았으나 대두유, 들기름군과 같은 수준이었다. 뇌조직에서는 간에 차이가 거의없었다. 간조직의 $\alpha$-tocopherol 농도와 환원형의 glutathione(GSH) 의 농도가 어미쥐에서 타군에 비해 현저히 낮았고, 새끼쥐에서도 $\alpha$-tocopherol 경우는 같은경향이나 그 정도가 덜 현저하며, GSH의 경우는 타군들과 차이가 없었다. 산화형 glutathioe (GSSG)의 농도는 어미쥐, 새끼쥐모두에서 식이지방에 따른 차이가 일관성 있게 나타나지 않았다. Glutathione peroxidase 활성은 간장과 뇌조직에서 성장과정중의 새끼쥐들에서 모두 약간씩 증가하였고, 채종유군에서 타군에 비해 증가정도가 낮아 활성이 39일에 현저히 낮았다. Superoxide dismutase 의 활성은 성장기간에 따른 변화는 적었고, 고등어유군이 타군에 비해 비교적 낮은값을 유지하였다. 어미쥐와 17일째 새끼쥐에서는 달리 26일과 39일째 새끼쥐의 간조직 glutathioe peroxidase 의활성이 지질과산화물 농도와 정의 상관관계가 보여져, 출생후 초기 성장과정에서 체내 적응성이 존재함을 나타내주었다.

• 한국식품영양과학회지
• /
• 제16권2호
• /
• pp.147-155
• /
• 1987

어유(魚油)에 포함된 $C20{\sim}22({\omega}3)$ 지방산을 섭취하였을 때, 간과 뇌조직의 지질과산화물 형성 및 항산화기능을 조사하기 위하여, 고등어유를 식이함량에 10%(w/w)되게 조제한 사료를, 70g 외의 암, 수컷의 취에게 주어 3개월간 사육하였다. 이 결과를 ${\omega}3$지방, ${\omega}6$지방, ${\omega}9$지방 및 포화지방과 비교하기 위하여, 다른 4군의 암, 수컷의 쥐들에게 들기름, 대두유, 채종유 및 쇠기름을 각각 첨가한 조제식이를 주어 같은 기간동안 사육하였다. 간조직의 지질과산화들 농도가 고등어유군에서 현저히 높은 반면, ${\alpha}-tocopherol$과 환원형 glutathione (GSH)의 양은 낮았다. 이 현상은 암컷에서가 숫컷에서보다 분명히 드러났고, 고등어유군 외의 타군간의 차이는 숫컷에서 약간 보여 졌으나 일관성은 없었다. 모든 식이군의 간조직 GSH농도는 숫컷에서가 암컷에서보다 낮았으나 산화형 glutathione (GSSG) 농도는 식이나 성에 따른 차이가 없었다. 뇌조직에서는 식이지방에 따른 지질과산화물과 ${\alpha}-tocopherol$ 농도의 차이가 발견되지 않았다. 간과 뇌의 양 조직에서 glutathione peroxidase나 superoxide dismutase의 활성이 식이에 따라 변화는 없었으나 glutathione peroxidase의 활성은 숫컷에서가 암컷에서보다 일관성있게 낮았다. 따라서 이 연구에서는 성(性)에 따른 항산화 기능에 차이가 있다는 것을 밝혔으며, 어유(魚油)를 통하여 C2O 이상의 ${\omega}3$ 다불포화지방산를 섭취할 때, 총 불포화도가 유사하거나 높은 $C18:2({\omega}6)$나 $C18:3({\omega}3)$ 지방산 섭취시보다 체내에서 많은 지질과산화들을 형성하며, 그에 따른 항산화물질의 소모가 크다는 것이 주목된다고 하겠다.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
• /
• pp.161-161
• /
• 2001

Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is an antioxidant selenoenzyme which interacts directly with and diminishes peroxidized phospholipids, cholesterol and cholesteryl ester in tissues. PHGPx activity appears in most tissues, but is especially high in testis. In testis, PHGPx level decreases in hypophysectomized rats but is partially restored after gonadotropin treament.(omitted)

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2003년도 추계학술대회
• /
• pp.189-189
• /
• 2003

Recent studies suggest that inflammatory events are implicated in a variety of human diseases including cancer and neurodegenerative diseases. It has been reported that expression of inducible cyclooxygenase (COX) and nitric oxide (NO) synthase and subsequent production of prostaglandins (PG)s and NO, respectively are elevated in many inflammatory disorders.(omitted)

• 약학회지
• /
• 제53권6호
• /
• pp.314-320
• /
• 2009

We examined metabolic conversion of cysteine into glutathione (GSH) and taurine in rat liver under oxidative stress. Administration of tert-butylhydroperoxide (t-BHP) into the portal vein of male rats resulted in a rapid elevation of serum sorbitol dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities, which decreased gradually in 24 hr. Hepatic cysteine concentration was reduced in 3 hr, and recovered progressively, reaching a level greater than 200% of the normal value in 24 hr. GSH was increased both in liver and blood at 9 hr after t-BHP challenge, whereas hypotaurine or taurine was not altered. $\gamma$-Glutamylcysteine synthetase (GCS) activity was increased from 9 hr after t-BHP treatment, but protein expression of the GCS-heavy subunit was not changed in liver. Activity or expression of cysteine dioxygenase was not affected by t-BHP treatment. Taken together, these data show that an acute oxidant challenge to the rats may induce upregulation of cysteine availability and GCS activity, resulting in an enhancement of hepatic GSH synthesis, but the increased cysteine level does not stimulate taurine synthesis via cysteine sulfinate pathway. It is indicated that the regulation of GSH and taurine biosynthesis from cysteine is not solely dependent on the cysteine concentration in rat liver under oxidative stress.

• 한국식생활문화학회지
• /
• 제19권1호
• /
• pp.52-60
• /
• 2004

This study was performed to investigate the effect of Lycii fructus beer on serum lipid profiles and antioxidant activity in rat Sprague-Dawley (SD) rats weighting about 190g were divided into the following 5 groups ; distillate water (Control), 5% ethanol in distillate water (Ethanol), commercial beer (CB), Lycii fructus beer (LFB) and 5% alcohol red wine diluted with distillate water (RW). Body weight, total food intake, FER and percent organ (liver, kidney) weight per body weight were not significantly changed by Lycii fructus beer drinking. After 6 weeks, serum total cholesterol, triglyceride and HDL cholesterol level were not significantly different. But, Lycii fructus beer intake tended to decrease serum triglyceride level and atherogenic index. Also, GOT and GPT levels were expressed lower than Ethanol group. There was not significantly different in hepatic glutatiione (GSH) content and glutathione-S-transferase (GST) activities among 5 groups. Lipid peroxidation in the hepatic was decreased by Lycii fructus beer intake. The results demonstrated that Lycii fructus beer was potential and effective antioxidant that can protect the decrease associated with alcohol.

• Journal of Nutrition and Health
• /
• 제35권2호
• /
• pp.183-191
• /
• 2002

The purpose of this study was to investigate the effect of dietary mushroom powder on blood glucose levels, seam lipid levels, glucose 6-phosphtase (G6Pase), thiobarbituric arid reactive substance (TBARS) and glutathione enzymes in diabetic rats treated with streptozotocin (STZ). Four groups of rats (Sprague-Dawley male rats, 180-200 g) were fed as follows: normal rats were fed a control diet (C), diabetic rats were file a control diet (CD), normal fats were fed a mushroom powder diet (M), and diabetic rals were find mushroom powder diet (MD). Diabetes was induced by single injection of streptozotocin (60 mg/kg B.W.). The animals were fed ad libium each of the experimental diets for five weeks. Food and water intake was determined every day. Blood glucose and serum total cholesterol levels were determined every week. After five weeks, the rats were sacrificed and blood glucose, serum total cholesterol, triglyceride levels and glutathione enzymes were measured. HDL-cholesterol levels were analyzed and LDL-cholesterol concentrations were calculated by equation. There was body weight loss in the diabetic rats, but the MD group showed less body weight loss than the CD group. Blood glucose and serum total cholesterol level of the MD group were lower than those of the CD group (p < 0.05). Also, serum total cholesterol of the M group was lower than that of the C group (p < 0.05). But the serum triglyceride level of the diabetic rats (CD and MD) was higher than that of the normal rats (C and M). However, there was no significant difference between the control diet group and the mushroom diet group. Serum HDL-cholesterol levels of the C group and CD group were higher than that of the M group (p < 0.05), and the MD group was not significantly different. But the serum LDL-cholesterol levels of the M group were lower than those of the C group (p < 0.05). Activity of hepatic microsomal G6Pase significantly increased in the CD and MD, reaching levels higher than those of the C and M groups. Hepateic gutathione S-transferase (GST, glutathione reductase (GR) and glutathione peroxidase (GPX) activity was not significant. But renal GST, GR and GPX activity in the MD group was lower than that of the CD group (p < 0.05). These results suggest that dietary mushroom reduces renal disorders such as oxidation and aging of tissue. In conclusion, dietary mushroom groups reduced blood glucose and cholesterol levels in STZ-induced diabetic rats and renal glutathione enzymes activity was averted in diabetic rats.