• Title/Summary/Keyword: Toxicity Reduction

Search Result 448, Processing Time 0.028 seconds

Acute Toxicity of the BKCa Channel Opener LDD175

  • Choi, Ji-Young;Choi, Jong-Hyun;Lee, Geum-Seon;Ko, Hong-Sook;Park, Chul-Seung;Kim, Yong-Chul;Cheong, Jae-Hoon
    • Biomolecules & Therapeutics
    • /
    • v.14 no.4
    • /
    • pp.253-258
    • /
    • 2006
  • LDD175(4-choloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-l-carboxylic acid) is one of benzofuroindole derivatives that act as a potent $BK_{Ca}$ channel openers. In the process of testing LDD175 as a new drug candidate, an acute toxicity study was carried out in mice. The mice were administered LDD175 intraperitoneally at dose of 0.2, 1, 10, 50, 100, 200, 400, 800mg/kg and orally at dose of 10, 100, 400, 800mg/kg body weight. After administering LDD175, the vital organs such as the liver, kidney and spleen were carefully observed for any significant pathological features or differences from the norm over a l4-day period. LDD175 did not induce any short-term toxicity at doses less than 100mg/kg. A $LD_{50}$ of LDD175 was 2493mg/kg in male mice and 4908mg/kg in female mice. Weight reduction was observed at a dose of 800mg/kg in male, and 400 and 800mg/kg in female. The kidney weight decreased in females after an intraperitoneal injection of LDD175 high dose(>400mg/kg, i.p.), and the spleen weight increased in the male(800mg/kg, i.p.) and female(400mg/kg, i.p.) mice. Inspite of the change in organ weights, there were neither histopathological changes nor any gross morphological abnormalities detected in any organ. LDD175 did not produce significant changes in the general behavior at doses of <200mg/kg, but decreased locomotor activity was observed at an intraperitoneal dose of 400mg/kg. Its effects on the locomotor activity and activity on the rotarod were tested and compared with the effects of diazepam 5mg/kg. The decrement in the locomotor activity and the activity on the rotarod induced by LDD175 was less serious than it by diazepam.

Asymmetric Bioconversion of Acetophenone in Nano-Sized Emulsion Using Rhizopus oryzae

  • Li, Qingzhi;Shi, Yang;He, Le;Zhao, Hui
    • Journal of Microbiology and Biotechnology
    • /
    • v.26 no.1
    • /
    • pp.72-79
    • /
    • 2016
  • The fungal morphologies and pellet sizes were controlled in acetophenone reduction by Rhizopus oryzae. The acetophenone conversion and (S)-phenylethanol enantiomeric excesses (e.e.) reached the peak after 72 h of incubation when using pellets with 0.54 mm diameter, which showed an excellent performance compared with suspended mycelia, clumps, and pellets with 0.65 or 0.75 mm diameter. Furthermore, nano-sized acetophenone was used as a substrate to improve the performances of biotransformation work. The results showed that the conversion of nanometric acetophenone and (S)-phenylethanol e.e. reached the maximum (both >99%) after 32 h of incubation when using 0.54 mm diameter pellets, at least 24 h in advance of the control group. On the other hand, Tween 80 and 1, 2-propylene glycol showed low or no toxicity to cells. In conclusion, pellets and acetophenone nanoemulsions synergistically result in superior performances of acetophenone reduction.

Kahweol inhibits lipid accumulation and induces Glucose-uptake through activation of AMP-activated protein kinase (AMPK)

  • Baek, Jung-Hwan;Kim, Nam-Jun;Song, Jun-Kyu;Chun, Kyung-Hee
    • BMB Reports
    • /
    • v.50 no.11
    • /
    • pp.566-571
    • /
    • 2017
  • Weight loss ${\geq}5$ percent is sufficient to significantly reduce health risks for obese people; therefore, development of novel weight loss compounds with reduced toxicity is urgently required. After screening of natural compounds with anti-adipogenesis properties in 3T3-L1 cells, we determined that kahweol, a coffee-specific diterpene, inhibited adipogenesis. Kahweol reduced lipid accumulation and expression levels of adipogenesis and lipid accumulation-related factors. Levels of phosphorylated AKT and phosphorylated JAK2, that induce lipid accumulation, decreased in kahweol-treated cells. Particularly, kahweol treatment significantly increased AMP-activated protein kinase (AMPK) activation. We revealed that depletion of AMPK alleviated reduction in lipid accumulation from kahweol treatment, suggesting that inhibition of lipid accumulation by kahweol is dependent on AMPK activation. We detected more rapid reduction in blood glucose levels in mice administrated kahweol than in control mice. We suggest that kahweol has anti-obesity effects and should be studied further for possible therapeutic applications.

Extracellular synthesis of silver nanoparticle by Pseudomonas hibiscicola - Mechanistic approach

  • Punjabi, Kapil;Mehta, Shraddha;Yedurkar, Snehal;Jain, Rajesh;Mukherjee, Sandeepan;Kale, Avinash;Deshpande, Sunita
    • Advances in nano research
    • /
    • v.6 no.1
    • /
    • pp.81-92
    • /
    • 2018
  • Biosynthesis of nanoparticles has acquired particular attention due to its economic feasibility, low toxicity and simplicity of the process. Extracellular synthesis of nanoparticles by bacteria and fungi has been stated to be brought about by enzymes and other reducing agents that may be secreted in the culture medium. The present study was carried out to determine the underlying mechanisms of extracellular silver nanoparticle synthesis by Pseudomonas hibiscicola isolated from the effluent of an electroplating industry in Mumbai. Synthesized nanoparticles were characterized by spectroscopy and electron microscopic techniques. Protein profiling studies were done using Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (1D-SDS PAGE) and subjected to identification by Mass Spectrometry. Characterization studies revealed synthesis of 50 nm nanoparticles of well-defined morphology. Total protein content and SDS PAGE analysis revealed a reduction of total protein content in test (nanoparticles solution) samples when compared to controls (broth supernatant). 45.45% of the proteins involved in the process of nanoparticle synthesis were identified to be oxidoreductases and are thought to be involved in either reduction of metal ions or capping of synthesized nanoparticles.

Copper ion Toxicity Causes Discrepancy between Acetate Degradation and Methane Production in Granular Sludge

  • Bae, Jin-Woo;Rhee, Sung-Keun;Jang, Am;Kim, In-S.;Lee, Sung-Taik
    • Journal of Microbiology and Biotechnology
    • /
    • v.12 no.5
    • /
    • pp.849-853
    • /
    • 2002
  • Metal ions have an adverse effect on anaerobic digestion. In an acetate degradation test of upflow of anaerobic sludge blanket granules with $Cu^{2+}$, not all of the acetate that disappeared was stoichiometrically converted to methane. In the presence of 400 mg/g-VSS (volatile suspended solids) $Cu^{2+}$, only 26% of the acetate consumed was converted to methane. To study acetate conversion by other anaerobic microorganisms, sulfate and nitrate reductions were investigated in the presence of $Cu^{2+}$ Sulfate and nitrate reductions exhibited more resistance to $Cu^{2+}$than methanogenesis, and the granules reduced 2.2 mM and 5.4 mM of nitrate and sulfate, respectively, in the presence of 400 mg/g-VSS copper ion. However, the acetate degraded by sulfate and nitrate reductions was only 24% of the missing acetate that could have been stoichiometrically converted to $CO_2$. Accordingly, 76% of the acetate consumed appeared to have been converted to other unknown compounds.

In vitro Alternatives to Skin Irritation Test

  • Shin, Dae-Sup;Kim, Dai-Byung;Ryu, Seung-Rel;Lee, Sun-Hee;Koh, Jae-Sook;Park, Won-Sae;Kim, Pu-Young
    • Biomolecules & Therapeutics
    • /
    • v.3 no.3
    • /
    • pp.242-244
    • /
    • 1995
  • In vitro cell culture system has been proposed as a promising alternative model to in vivo skin irritation test. These studies were performed to screen the cytotoxicity effects of surfactants using normal human skin fibroblasts. Cell membrane integrity assessed by the leakage of lactate dehydrogenase (LDH) and mitochondrial integrity by MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromides reduction test were affected in a dose dependent manner. The irritation potential of surfactants to human skin patch test, and the changes of capillary permeability by rabbit intradermal safety test were assessed as in vivo methods. Our results suggest that LDH leakage assay and MTT reduction test using cultured human fibroblasts could be predictive for the irritancy of various surfactants in human, and LDH assay is superior correlated with in vivo test (r=0.886) to MTT test with in vivotest (r=0.757).

  • PDF

Iron Toxicity to Peritoneal Macrophage Due to Alteration of Mitochondria by NO

  • Yoon, Ji-Yeon;Kim, Jin-Sun;Lee, Heum-Sook;Lee, Kyo-Young;Cheon, Choong-Ill;Lee, Myeong-Sok;Park, Jong-Hoon;Song, Eun-Sook
    • Animal cells and systems
    • /
    • v.8 no.2
    • /
    • pp.97-103
    • /
    • 2004
  • The cytotoxic effect of iron was examined in peritoneal macrophage to determine contributing factors by iron injection to rat. Viability was reduced by 24% by the iron-overload and by 30% by short-term iron addition. Total iron was increased by 45% in the iron-overloaded with remarkable elevation (9 to 14 fold) in the presence of $FeSO_4$. Free calcium was also increased by 19% in control and 44% in iron-overloaded group due to additional $FeSO_4$ NO and MDA were increased by 40% and 136%, respectively, with significant reduction (37%) of NAD(P)H. RCR and cytochrome c oxidase activity were lowered approximately by 10% with reduction of mitochondrial membrane potential. Addition of iron was frequently associated with altered distribution of mitochondria of high membrane potential in the iron-overloaded macrophage. These results suggest altered mitochondria with high NO and low NAD(P)H due to iron.

Characterization of Copper Toxicity Symptoms and Determination of Tissue Critical Concentration for Diagnostic Criteria in Korean Bred Strawberries (국내육성 주요 딸기 품종에서 발생하는 구리(Cu) 과잉 증상 및 영양진단을 위한 식물체 내 한계농도)

  • Choi, Jong Myung;Nam, Min Ho;Lee, Chiwon W.
    • Horticultural Science & Technology
    • /
    • v.30 no.5
    • /
    • pp.477-483
    • /
    • 2012
  • This study was carried out to investigate the influence of copper concentrations in fertilizer solution on the growth of and nutrient uptake by domestically bred strawberries. The characterization of toxicity symptoms as well as tissue analyses based on dry weight of above ground tissue were also conducted to determine the threshold levels in plants when toxicity developed in copper. The dry weights of the above ground tissue were not significantly different among the treatments of 0.25 mM to 1.0 mM in 'Keumhyang' and 'Maehyang' strawberries and that of 0.25 mM to 3.0 mM in 'Seolhyang' strawberry. This indicates that the 'Seolhyang' strawberry is more tolerant to copper toxicity than 'Keumhyang' or 'Maehyang' strawberries. Application of copper at high concentrations resulted in severe toxicity such as death of extensive areas of leaves. The lower leaves became yellow and die rapidly as the symptoms spread up the plants. The leaf blades and petioles died back to the crown and hang on by mechanical attachment. Symptoms of copper toxicity in lower leaves developed as browning on leaf margins and in patches between leaf veins that became necrotic. The elevation of copper concentrations in fertilizer solution did not influence the tissue phosphorus, potassium, calcium, and magnesium contents based on the dry weight of the above ground tissue. The tissue copper contents increased lineally as the copper concentrations in fertilizer solution were elevated. But the tissue iron, manganese and boron contents were not influenced by the concentrations. When the concentration of copper at which growth of a plant is retarded by 10% is regarded as threshold level, the copper contents based on dry weight of above ground plant tissue should be lower than 71.4, 57.9 and 74.8 $mg{\cdot}kg^{-1}$ in 'Keumhyang', 'Maehyang' and 'Seolhyang' strawberries, respectively. The symptom characterization and established threshold level in copper toxicity would help growers to prevent the reduction of crop growth and yield in 'Seolhyang' strawberry cultivation.

The Toxic Effects of Mysid, Neomysis awatschensis Exposed to Organotin (유기주석 노출에 의한 Mysid, Neomysis awatschensis의 독성 영향)

  • 지정훈;김상규;황운기;강주찬
    • Environmental Analysis Health and Toxicology
    • /
    • v.17 no.4
    • /
    • pp.357-362
    • /
    • 2002
  • Tests for the toxicity of tributyltin (TBT) were conducted on mysid collected from Dadepo beach, Pusan, Korea. The toxic effects of tributyltin on the survival, growth and oxygen consumption of the mysid, Neomysis awatschensis have been evaluated. Mysids were exposed to several concentrations of TBT (0, 0.56, 1.15, 3.07 and 6.12 $\mu\textrm{g}$/L) for 6 weeks. Survival rate was decreased with increases in concentration and exposure time and the reduction of more than 40% occurred at TBT concentration greater than 1.15 $\mu\textrm{g}$/L after 6 weeks. Growth rate was significantly decreased at concentrations greater than 1.15 $\mu\textrm{g}$/L. Oxygen consumption rate was also decreased in a concentration-dependent way and significantly decreased to 39,47 and 69% of the control at 1.15, 3.07 and 6.12 $\mu\textrm{g}$/L, respectively. These results indicate that the contamination of aquatic environment by TBT has the potential to significantly reduce coastal and estuaries recruitment of mysids.

Distribution and Phytotoxicity of Mercury in Tomato Seedlings Exposed to Mercury

  • Cho, Un-Haing
    • The Korean Journal of Ecology
    • /
    • v.22 no.2
    • /
    • pp.89-94
    • /
    • 1999
  • Thirty-day-old seedlings of tomato (Lycopersicon esculentum) were treated with different concentrations of HgCl$_2$(0. 10 and 50 $\mu$M) for up to 20 days. and the detailed distribution of Hg absorbed and its toxicity in different plant parts (roots, stems and leaves) were investigated. The accumulation of Hg in plants increased with external Hg concentrations. and Hg is strongly retained by roots. Further. Hg content in leaves was various. showing more accumulation in older leaves. Seedlings exposed to toxic levels of Hg showed not only the reduction of dry weight and length of both shoot and root. and chlorophyll levels in leaves but also the enhancement of malondialdehyde (a lipid peroxidation product) formation in all plant parts investigated. These results suggest that physiological impairment of a plant exposed to Hg may be achieved by internal distribution of Hg absorbed and Hg-induced oxidative stress in different plant parts.

  • PDF