Benzene increases the ratio of arachidonic acids to docosahexaenoic acids and inhibits the de novo synthesis of ceramide in the rat liver

Sul, Donggeun,Shim, Ilsub,Im, Hosub,Won, NamHee,Kim, Hae-Joon,Lee, Eunil WILEY 2005 Journal of Applied Toxicology Vol. No.

<P>The present study investigated the effects of inhalation exposure of benzene at 0, 10, 200 and 600 ppm for 1, 2 and 4 weeks on n-6 and n-3 fatty acids and ceramide levels in the rat liver. No signicant difference in the ratio of saturated fatty acid to unsaturated fatty acid was found on increasing benzene exposure levels, but the ratio of saturated fatty acid to unsaturated fatty acid decreased with increasing benzene exposure times, with the exception of the phospholipids of rats exposed to 200 and 600 ppm of benzene. A signicant increase in the ratio of arachidonic acid to docosahexaenoic acid was found in the phospholipids of rats exposed to 200 and 600 ppm of benzene for 4 weeks. In our study, no change in the relative amounts of sphingomyelin in phospholipids, due to benzene exposure at 600 ppm for 4 weeks resulted in the lack of sphingomyelin turnover. However, ceramide levels in the livers of rats exposed to 600 ppm of benzene for 4 weeks were signicantly reduced upon increasing the benzene concentration. This result shows that the de novo synthesis of ceramide was signicantly inhibited at higher levels of benzene and that the ratio of arachidonic acid to docosahexaenoic acid in phospholipids is dose-dependently related to benzene exposure. Copyright © 2005 John Wiley & Sons, Ltd.</P>

DNA damage in T- and B-lymphocytes of rats exposed to benzene

Donggeun Sul,Doyoung Lee,Gyu-Chan Jo,Hosub Im,Hyungho Hong,Dukjin Jo,Chan-wha Kim,Hae-Joon Kim,Eunil Lee 한국환경성돌연변이발암원학회 2002 한국환경성돌연변이·발암원학회지 Vol.22 No.4

Single cell gel electrophoresis assay was carried out to evaluate DNA damage in T-and Blymphocytes from rats exposed to benzene and the correlation between DNA damage and the level of t,t-muconic<br/> acids, which are urinary benzene metabolites, was investigated. In control rats, the mean values of Olive tail moments in T- and B-lymphocytes were 1.507±0.187 and 1.579±0.206 respectively. DNA damages of T-lymphocytes in rats exposed for 4 weeks showed the highest Olive tail moments at each benzene concentration examined (2.72-4.351). However this DNA damage was decreased after 6 weeks of exposure (1.74-2.09). DNA damages of B-lymphocytes did not show such differences with exposure time or benzene concentration (1.49-2.07) except at 200 ppm at 4 weeks. T-lymphocytes show significantly more damages than B-lymphocyte upon acute exposure to benzene.

Delphinidin Ameliorates Beta-Amyloid-Induced Neurotoxicity by Inhibiting Calcium Influx and Tau Hyperphosphorylation

KIM, Hyo-Shin,SUL, Donggeun,LIM, Ji-Youn,LEE, Dongho,JOO, Seong Soo,HWANG, Kwang Woo,PARK, So-Young Japan Society for Bioscience, Biotechnology, and A 2009 Bioscience, Biotechnology, and Biochemistry Vol.73 No.7

<P>Beta-amyloid (Aβ) has been suggested to induce neurotoxicity in Alzheimer’s disease. We evaluated the neuroprotective effects of delphinidin, an anthocyanidin commonly present in pigmented fruits and vegetables, against Aβ-induced toxicity. Aβ (25–35) significantly decreased the viability of PC12 cells, and this was accompanied by an increase in intracellular calcium levels and tau phosphorylation. However, treatment with delphinidin rescued PC12 cells from Aβ by attenuating the elevation of intracellular calcium levels and tau phosphorylation. Taken together, these results suggest that delphinidin protects PC12 cells against Aβ-induced toxicity by attenuating intracellular calcium influx and tau hyperphosphorylation.</P>

Strategies Against Human Papillomavirus Infection and Cervical Cancer

Jung Woon-Won,Chun Taehoon,Sul Donggeun,Hwang Kwang Woo,Kang Hyung-Sik,Lee Duck Joo,Han In-Kwon The Microbiological Society of Korea 2004 The journal of microbiology Vol.42 No.4

Papillomaviruses infect a wide variety of animals, including humans. The human papillomavirus (HPV), in particular, is one of the most common causes of sexually transmitted disease. More than 200 types of HPV have been identified by DNA sequence data, and 85 HPV genotypes have been well char­acterized to date. HPV can infect the basal epithelial cells of the skin or inner tissue linings, and are, accordingly, categorized as either cutaneous or mucosal type. HPV is associated with a panoply of clin­ical conditions, ranging from innocuous lesions to cervical cancer. In the early 1980s, studies first reported a link between cervical cancer and genital HPV infection. Genital HPV infections are now rec­ognized to be a major risk factor in at least $95\%$ of cervical cancers. 30 different HPV genotypes have been identified as causative of sexually transmitted diseases, most of which induce lesions in the cervix, vagina, vulva, penis, and anus, as the result of sexual contact. There is also direct evidence demon­strating that at least four of these genotypes are prerequisite factors in cervical cancer. The main aim of this review was to evaluate the current literature regarding the pathovirology, diagnostics, vaccines, therapy, risk groups, and further therapeutic directions for HPV infections. In addition, we reviewed the current status of HPV infections in South Korean women, as evidenced by our data.

The inhibitory effect and the molecular mechanism of glabridin on RANKL-induced osteoclastogenesis in RAW264.7 cells.

Kim, Hyun-Sook,Suh, Kwang Sik,Sul, Donggeun,Kim, Byung-Jo,Lee, Seung Kwan,Jung, Woon-Won D.A. Spandidos 2012 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.29 No.2

<P>Osteoblastic bone formation and osteoclastic bone resorption are in balance to maintain a constant, homeostatically controlled amount of bone. Excessive bone resorption by osteoclasts is involved in the pathogenesis of bone-related disorders. In the present study, we evaluated the inhibitory effects of glabridin, a flavonoid purified from licorice root, on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and its molecular mechanisms in murine osteoclast progenitor RAW264.7 cells. Glabridin significantly inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity, the formation of multinucleated osteoclasts and resorption-pit formation. In mechanistic studies of the anti-osteoclastogenic potential of glabridin, we found that glabridin inhibited RANKL-induced expression of c-Fos and subsequent expression of NFATc1, which is a master regulator of osteoclastogenesis. Interestingly, glabridin inhibited the RANKL-induced expression of signaling molecules (TRAF6, GAB2, ERK2, JNK1 and MKK7) and osteoclast survival-related signaling pathways such as c-Src, PI3K and Akt2. Glabridin also inhibited the bone resorptive activity of mature osteoclasts by inhibiting osteoclast-associated genes (cathepsin?K, MMP-9, CAII, TCIRG1, OSTM1 and CLCN7). Taken together, our data suggest that glabridin holds great promise for use in preventing osteoclastogenesis by inhibiting RANKL-induced activation of signaling molecules and subsequent transcription factors in osteoclast precursors and these findings may be useful for evaluating treatment options in bone-destructive diseases.</P>

DNA Damage in T and B Lymphocytes, Bone Marrow, Spleens, and Livers of Rats Exposed to Benzene

Lee, Eunil,Im, Hosub,Oh, Eunha,Jung, Woon-Won,Kang, Hyung-Sik,Sul, Donggeun Taylor Francis 2005 Inhalation toxicology Vol.17 No.7

<P>Single-cell gel electrophoresis assays were performed in order to evaluate DNA damage occurring in the T and B lymphocytes, spleens, bone marrow, and livers of rats exposed to benzene at a concentration of 100, 200, or 400 ppm for 2 or 4 wk. The level of t , t -muconic acid ( t , t -MA), which is a urinary benzene metabolite, was determined. In the control rats, mean Olive tail moments in the T and B lymphocytes were 1.507 ± 0.398 and 1.579 ± 0.206, respectively. DNA damage in the T and B lymphocytes exposed to 400 ppm benzene for 4 wk caused those rats to exhibit the highest Olive tail moments, with their values measured as 4.351 ± 0.510 and 3.140 ± 0.631, respectively. Also, the t , t -MA levels increased directly with increasing benzene exposure time and dose during the 4 wk. After 4 wk, the levels of t , t -MA in urine from rats exposed to 100, 200, and 400 ppm were 19.30 ± 5.62, 30.36 ± 4.46, and 46.93 ± 9.10 mg/g creatinine. In conclusion, the present study demonstrates that benzene exposure results in significant DNA damage in the T and B lymphocytes, bone marrow, spleens, and livers of rats. DNA damage in the blood cells and organs was also discovered to vary directly with benzene exposure, in both a dose-dependent and time-dependent manner. In addition, a similar trend regarding DNA damage was found in the blood cells and organs, and evidenced a good association with the level of t , t -MA in the urine.</P>

An Evaluation of the Neonatal Immune System Using a <i>Listeria</i> Infection Model

Byun, Hyun-Jung,Jung, Woon-Won,Lee, Jong-Bae,Chung, Hee Yong,Sul, Donggeun,Kim, Sang Joon,Park, Chung-Gyu,Choi, Inho,Hwang, Kwang Woo,Chun, Taehoon S. Karger AG 2007 NEONATOLOGY Vol.92 No.2

<P><I>Background:</I> T helper 1 (Th1)/T helper 2 (Th2)-biased cytokine regulation may be another reason that neonates are much more susceptible to infectious disease than are adults. <I>Objectives:</I> We attempted to determine the ability of neonatal mice to direct the Th1 phenotype against <I>Listeria monocytogenes</I> (LM), because LM, an intracellular Gram-positive bacterium, induces profound cellular immunity by Th1 cells in vivo. <I>Methods:</I> In order to determine whether neonatal mice evidence strong Th1 activity during LM infection, neonatal mice were compared with adult mice with regard to susceptibility to LM, cytotoxic T lymphocyte activity, and cytokine profiles. Neonatal gene profiles relevant to Th1 and Th2 differentiation during LM infection were also compared between neonatal and adult mice, via real-time PCR and RT-PCR. <I>Results:</I> Neonatal mice were found to be far more susceptible to LM infection than adult mice, due to a lack in the induction of cytotoxic T cell activity, coupled with poor IFN-γ secretion. Further, LM-infected neonatal mice evidenced much lower levels of expression of Th1-type immune components, including IL-12, IFN-γ, Delta-4 and T-bet, as compared to those features in adult mice. These results may be due to the comparably lower expressions of mannose-bind lectins and some of toll-like receptors (TLRs) such as TLR-5, -6 and -9, necessary mediators to develop Th1 immune responses. <I>Conclusions:</I> Neonatal mice may not mount an adequate Th1 type immune response due to a significantly lower expression of Th1-type immune components as compared to adult mice, even when forced into a Th1-prone environment.</P><P>Copyright © 2007 S. Karger AG, Basel</P>

Thermosensitive and mucoadhesive delivery systems of mucosal vaccines

Han, In-Kwon,Kim, Young Bong,Kang, Hung-Sik,Sul, Donggeun,Jung, Woon-Won,Cho, Hee Jeong,Oh, Yu-Kyoung Elsevier 2006 Methods Vol.38 No.2

<P><B>Abstract</B></P><P>Mucosal vaccination is emerging as a potential administration route for eliciting antigen-specific mucosal and systemic immunogenicity. Most mucosal vaccines have been administered in a phosphate-buffered saline vehicle that may limit the exposure of antigens to the mucosal surfaces and result in poor immunogenicity. To improve the potency of the mucosal vaccines, we have developed mucosal vaccine delivery systems that might prevent leakage and increase retention of vaccines on mucosal surfaces. Thermosensitive polymers have been used to reduce the leakage problems of nasal or vaginal vaccines, while mucoadhesive polymers have been employed to increase the mucosal contact of the vaccines. Here, we describe the formulation and delivery methods of mucosal vaccines using thermosensitive and mucoadhesive polymers.</P>

Subacute inhalation toxicity assessment of fly ash from industrial waste incinerators

Shim, Ilseob,Oh, Eunha,Yang, Sangyoung,Ryu, Taekwon,Soh, Jaewon,Sul, Donggeun,Kim, Pilje Informa Healthcare 2012 Inhalation toxicology Vol.24 No.11

<P>Fly ash from industrial waste incinerators has been a significant concern because of their constituent toxic heavy metals and organic compounds. The objective of this study was to identify the subacute inhalation toxicity of fly ash from industrial waste incinerators, using whole body inhalation exposure chambers. Male and female groups of Sprague-Dawley rats were exposed to fly ash by inhalation of concentrations of 0, 50, 100, 200 mg/m<SUP>3</SUP>, for 6 h/day, 5 days/week for 4 weeks. There was no significant difference in body weight, and relative organ weight to body weight, between the exposure groups and the control group. Hematological examinations revealed a significant increase of monocyte counts in fly ash exposed rats and brown pigment laden macrophage was found in the lungs of rats exposed to high concentration of fly ash. A decrease of blood glucose levels and an increase in glutamate oxaloacetate transaminase activity were observed in fly ash treated rats. There was also a significant increase of lactate dehydrogenase levels in rat blood exposed fly ash. A significant dose-dependent increase of DNA damage was found in lymphocytes, spleen, bronchoalveolar lavage, liver, lung, and thymus of rats exposed to fly ash. In addition, the level of lipid peroxidation was increased in the plasma of rats exposed to a high concentration of fly ash. These results suggest that inhalation of fly ash from industrial waste incinerators can induce histopathologic, hematological, and serum biochemical changes and oxidative damage.</P>

Mitomycin-C Concentration in Cornea and Aqueous Humor and Apoptosis in the Stroma After Topical Mitomycin-C Application: Effects of Mitomycin-C Application Time and Concentration

Song, Jong-Suk,Kim, Jun-Heon,Yang, Minho,Sul, Donggeun,Kim, Hyo-Myung Masson Pub. USA 2007 Cornea Vol.26 No.4

PURPOSE:: To evaluate the effects of the applied mitomycin-C (MMC) concentration and application time on the aqueous MMC concentration and apoptosis in the corneal stroma. METHODS:: New Zealand white rabbits underwent mechanical epithelium debridement of the central 7.5 mm of the cornea. A sponge soaked in MMC solution was placed on the denuded corneal stroma. The effect of the exposure times ranging from 15 to 120 seconds and the different MMC concentrations ranging from 0.005% to 0.04% on the aqueous MMC concentration and the apoptosis in the stromal cells were evaluated. RESULTS:: The aqueous concentration of MMC increased linearly with increasing exposure time and MMC concentration. The correlation between the aqueous MMC concentration and the applied concentration (r = 0.809, P < 0.001) was higher than the correlation between the aqueous MMC concentration and the application time (r = 0.693, P < 0.001). Terminal deoxyribonucleotidyltransferase-mediated dUTP-digoxigenin nick end labeling (TUNEL)-positive cells were detected in the superficial stroma of the central denuded cornea. The numbers of TUNEL-positive cells increased linearly with increasing concentrations, and the increase was statistically significant (P = 0.026). However, the numbers of TUNEL-positive cells increased only slightly with an increasing application time, and the increase was not statistically significant (P = 0.928). CONCLUSIONS:: Reducing the applied concentration or decreasing the exposure time might be a good modality for reducing the potential MMC toxicity. The applied MMC concentration had greater effects on the aqueous MMC concentration and apoptosis in the stromal cells than the exposure time.