• Nutritional Sciences
• /
• v.7 no.4
• /
• pp.189-195
• /
• 2004

1bis study investigated the antioxidative effect in kidney of senescence-accelerated prone SAMP8 mice with calorie restriction. 4-weeks-old SAMP8 female mice were divided into 4 groups according to the experimental feeding period: for 4, 8, 12 month, and at natural death. Each group was subdivided into 2 groups, with thirteen mice each one, as ad libitum group and as dietary restriction group (60% of ad libitum feeding amount). After feeding for a given period, the mice were sacrificed to get the following results: among the experimental groups, there wereno significant differences in xanthine oxidase (XOD) activity in their kidney tissues. The contents of cytochrome $P_{450}$ decreased in ad libitum group and dietary restriction group by age. The activity of NADPH-cytochrome $P_{450}$ reductase showed a trend similar to cytochrome $P_{450}$. Superoxide radical content increased with age. At the 4th, 8th and 12 months of the experimental period, the activity in the dietary restriction group was less than that of ad libitum group by as much as 17% 14% and 14% respectively. For hydrogen peroxide, the contents were increased in the ad libitum group with age, while no correlation between content and age was observed in the dietary restriction group. In the 8th and 12th months of the experimental period, the were in the dietary restriction group less than that of ad libitum group counterpart as much as 17% and 20o/c, respectively. For the cellular membrane stability of the kidney, no significant correlation with age was observed in either the dietary restriction group or the ad libitum group. However at the 12th month of the experiment, however, the stability in the dietary restriction group was 11 % higher than that in the ad libitum group. In conclusion, with these results obtained from the SAMP8 mouse model, we demonstrate that dietary restriction has the effects of anti-oxidation and anti-senescence in the kidney.

• Asian-Australasian Journal of Animal Sciences
• /
• v.15 no.3
• /
• pp.438-444
• /
• 2002

This study was conducted to investigate the effect of aflatoxin $B_1$ ($AFB_1$) alone or mixed function oxidase (MFO)-activated $AFB_1$ on various functions of mule duck peritoneal macrophages. Duck peritoneal macrophages were incubated with $AFB_1$ 0, 5, 10, 20, 50 and $100 {\mu}g/ml$ for 12 h. The cell viability significantly declined as the concentration of $AFB_1$ increased and more obviously detrimental effects was noticed in MFO-metabolized $AFB_1$ treatments. Either in opsonized or unopsonized Candida albicans, phagocytotic ability of macrophages was decreased with the elevation of the concentration of $AFB_1$. Significantly higher levels of macrophages were damaged in MFO-metabolized $AFB_1$ than $AFB_1$ alone in concentrations above $20{\mu}g/ml$. The cytotoxicity activity was in the range of 41 to 33% after exposure to $AFB_1$ 5 to $100{\mu}g/ml$, and a significant higher TNF-like substance secretion by lipopolysaccharide (LPS) stimulation was obtained. When LPS was present in the medium, the percentage of cytotoxicity was higher than all treatments of $AFB_1$ both with and without MFO-activation in the absence of LPS. The results suggest that MFO-metabolized $AFB_1$ can alter cell viability and morphology of duck macrophages more than $AFB_1$ administered alone. Both with and without MFOactivation, $AFB_1$ has detrimental effects on phagocytotic ability and TNF-like substance secretion, increasing with level of $AFB_1$.

• Environmental Analysis Health and Toxicology
• /
• v.3 no.3_4
• /
• pp.39-51
• /
• 1988

Effects of ${\alpha}$-tocopherol and perilla oil on the toxicity of polychlorinated biphenyls (PCB) in male rat were studied. Rats were fed ad libitum for 6 weeks with the animal diet which contains PCB 30 ppm and 100 ppm. Perilla oil (0.5 g/kg body weight) and ${\alpha}$-tocopherol (30 mg/kg body weight) were administered intraperitoneally twice a week for 6 weeks. Rats fed with PCB showed enlargement of liver and spleen, increase in aspartate aminotransferase, alkaline phosphatase, sereum lipid and cytochrome P 450 and decrease in body weight and glutathione. When perilla oil was administered to rats fed with PCB increase in aspartate aminotransferase, alkaline phosphatase, serum lipid and cytochrome P45O and decrease in body weight and glutathione were significantly augmented, compared to rats fed with PCB alone. This means that perilla oil potentiates the toxicity of PCB. On the other hand when ${\alpha}$-tocopherol was administered to rats fed with PCB increase in aspartate aminotransferase, alkaline phosphatase, serum lipid and cytochrome P45O and decrease in body weight and glutathione were signigicantly reduced, compared to rats fed with PCB alone. This means that u-tocopherol reduces the toxicity of PCB. From the above results, it may be concluded that PCB is metabolized by microsomal mixed function oxidase and the metabolite causes the toxicity and microsomal glutathione plays a role of protection on the toxicity of PCB.

• The Korean Journal of Pesticide Science
• /
• v.2 no.2
• /
• pp.10-15
• /
• 1998

The bimolecular inhibition rate constants of carbofuran and N-dimethylphosphinothioyl carbofuran(PSC) to acetylcholinesterase(AChE) were $7.7{\times}10^{5}\;M^{-1}{\cdot}min^{-1}$ and $1.2{\times}10^{3}\;M^{-1}{\cdot}min^{-1}$, respectively. These results showed that PSC required a bioactivation process for its toxic action because it didn't inhibit the target enzyme effectively. The potency of PSC as an inhibitor of AChE increased when PSC and AChE were incubated with microsomes fortified with NADPH compared with microsome alone. Piperonyl butoxide(PBO) addition to these coupled systems greatly reduced the inhibition of the target enzyme by blocking the bioactivation process. In vivo inhibition study of mouse brain AChE, $I_{50}$ value for AChE was 28 mg/kg for PSC and the value increased to 57 mg/kg when PBO was pretreated. This result showed that cytochrome $P_{450}$ would also play a role in the bioactivation process of PSC in vivo. And conversioin of carbofuran from PSC was 55 % in a chemical oxidation system using meta-chloroperoxybenzoic acid. The oxidative activation of PSC to carbofuran was shown to be essential for showing its toxicological action and cytochrome $P_{450}$ was identified as an important enzyme which participated in this process.

• Korean Journal of Environmental Biology
• /
• v.22 no.1
• /
• pp.177-183
• /
• 2004

Cytochrome P45O (CYP) contents and 7-ethoxyresorufin-O-deethylase (EROD) activity were determined in hepatic microsome of olive flounder (Paralichthys olivaceus) exposed to tributyltin chloride (TBTC), tributyltin oxide (TBTO), and triphenyltin chloride (TPTC). In addition, effects of in vivo (intraperitoneal injection of 7.5 mg $kg^{-1}$ BW) exposure of flounder to TPTC on CYP, NADPH cytochrome c reductase, NADH cytochrome b5 yeductase and EROD levels were measured. In in vitro exposure of hepatic microsome to organotins, TBTC, TBTO and TPTC reduced CYP contents and inhibited EROD activity. The TPTC was the strongest inhibitor, which is followed by TBTO and TBTC. The degree of inhibition, especially EROD acitivity, depended on the exposure duration. In addition, all the target enzymes in flounder were inhibited by TPTC with the in vivo exposure to TPTC. As EROD activity was the most sensitive to the inhibitions and demonstrated good reproducibility of the results, it could be used as a helpful tool toy monitor effects of organotin compounds on mixed funciton oxygenase system in marine fish.

• Korean Journal of Environmental Agriculture
• /
• v.10 no.2
• /
• pp.167-177
• /
• 1991

O-ethyl S-methyl ethylphosphonothioate [$LD_{50}$ (rat, oral) 4.6mg/kg ; $K_i$(bovine erythrocyte acetylcholinesterase) 303 $M^{-1\;min-1}$] was selected as a model compound to study the mode of action of O, S-dialkyl alkylphosphonothioates which have been hypothesized to be toxic via a bioactivation process. Two chemical oxidants, meta-chloroperoxybenzoic acid and monoperoxyphthalic acid, and rat liver microsomal oxidases were used to mimic the action of mixed function oxidases on the model compound. The formation of S-oxide, a very unstable active intermediate, was proposed based on the identification of metabolic products.Furthermore, a trapping experiment with ethanol showed that the unstable intermediate S-oxide had the ability to phosphorylate acetylcholinesterase which is an important enzyme in nerve systems. The S-oxide intermediates are presumed to be responsible for the toxicity of O,S-dialkyl alkylphosphonothioates.

• Korean journal of applied entomology
• /
• v.32 no.3
• /
• pp.291-299
• /
• 1993

Midgut tissues from 4 insect specIes were exammed for the activity of cytochrome P-450 monooxygenases, a major enzyme involved in chemical detoxification. When Helicoverpa assulta larvae were reared on an artificial d;et, the specific activity of the midgut cytochrome P-450 monooxygenases (MFO) was :3 times higher than that of the fat body, The specific activity of the midgut cytochrome P-450 monooxygenases was higher in H. assul/a larvae when reared on Nicotiana tabacum leaves than when on CapsIcum annuum fruits or an artificial diet. In the case of Hyphantria cunea larvae, Tilia megaphyllo leaves were the best in inducing midgut cytochrome P-450 monooxygenases activity. When larvae of H. assulta, Spodoptera exigua, H. cunea and Spodoptera litura were reared on their own artificial diet, the highest activity was seen in S. exigua larvae which is a polyphagous and insecticide-resistant strain.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1993.04a
• /
• pp.97-97
• /
• 1993

본 연구과제에서는 적출판류간실험법 (isolated perfused liver technique)을 약물의 간독성 유발 및 보간작용에 관한 실험법으로 개발하고자 butylated hydroxyanisole (BHA) 을 이용하여 보간실험을 하였다. BHA를 식이투여한 흰쥐로부터 적출한 간에 간독성 모델물질로 2,6-dichlorophenolindophenol (DCPIP) 을 관류시켜 관류액내의 DCPIP의 유리형, 환원형, glucuronide, sulfate 포합체의 대사체를 측정하여 DCPIP 외 대사양상을 관찰하였으며, 동시에 간세포 손상으로 관류액내로 유출된 lactate dehydrogenase (LDH)의 활성도를 측정하여 DCPIP예 의할 간세포독성 유발정도를 간접적으로 측정하여 대조군과 비교하였다. 그리고 BHA에 의한 보간작용이 약물대사효소의 변와에 기인한 것인가를 관찰하기 위하여 모델약물로 7-ethoxycoumarin (EC) 이나 EC의 phase I 대사산물인 7-hydroxycoumarin (HC) 을 관류시켜 관류액내의 HC의 유리체, glucuronide 포합체, sulfate 포합체로의 대사량을 측정하여 약물대사시 약물의 활성화에 관계하는 phase I mixed function oxidase (MFO) 효소와 약물의 해독화에 관계하는 phase II 포합효소 (UDP-glucuronyltranesferase(UDPGT)와 sulfotransferase (ST))의 활성도 변화를 측정하여 대조군과 비교하였다. 간독성 모델물질인 DCPIP를 적출한 흰쥐의 간에 관규시켰을때 BHA 전처리군이 LDH가 유출되기 시작하는 시간이 대조군에 비하여 유의적으로 늦었으며, LCH가 유출량도 유의적으로 감소되어 DCPIP에 의한 간독성 유발능력이 BHA에 의하여 감소됨을 관찰하였다. 아울러 DCPIP의 대사체중 환원체와 glucuronide 포합체의 생성량이 증가되어 BHA에 의하여 quinone reductase와 UDPGT 활성도가 증가되었음을 알 수 있었다. 그리고 BHA 전처리에 의하여 MFO효소계와 ST의 활성도에는 변화가 없었으나 UDOGT 의 활성도는 약 2.2배 증가되었다. 이상의 결과로 BHA에 의한 보간작용은 간독성 물질을 활성화시키는 phase I MFO 효소의 활성도에는 변화없이 해독작용에 관여하는 phase II효소들의 활성도 증가에 기인된 것을 알 수 있었다. 그리고 이러한 결과는 적출한 관류간실험법은 여러 약물의 보간효과를 관찰하는 실험법으로 적합할 것으로 사료되었다.

• Korean Journal of Veterinary Research
• /
• v.38 no.1
• /
• pp.17-28
• /
• 1998

Drug-metabolizing activities of Korean native cattle and swine were investigated from viewpoints of the cytochrome P-450's level, their dependent mixed function oxidase activities, the reactive oxygen species formation and cytosolic enzyme acitivities from each liver homogenates. Level of cytochrome P-450 in the liver microsome of Korean native cattle was $0.28{\pm}0.05nmole/mg$ and that in pigs $0.35{\pm}0.03nmole/mg$. Level of cytochrome $b_5$ of Korean native cattle was $0.24{\pm}0.06nmole/mg$, and that of pigs $0.2{\pm}0.05nmole/mg$, showing no difference between two species. NADPH P-450 reductase were higher in Korean native cattle ($58.3{\pm}5.3nmole/mg/min$) than in pigs ($29.9{\pm}3.8nmole/mg/min$)(p<0.01). The activities of cytochrome P-450 dependent monooxygenases such as ethoxyresorufin O-deethylase (cattle, $96.5{\pm}12.5nmole/mg/min$ ; pigs, $13.6{\pm}2.1nmole/mg/min$), N-benzphetamine N-demethylase (cattle, $5.23{\pm}0.82nmole/mg/min$ ; pigs, $0.76{\pm}0.3nmole/mg/min$) and aniline hydroxylase (cattle, $0.95{\pm}0.1nmole/mg/min$ ; pigs, $0.33{\pm}0.08nmole/mg/min$) were much higher in Korean native cattle than in swine(p<0.01). However, the activity of testosterone $7{\alpha}$-hydroxylase was higher in swine ($90.4{\pm}1.2nmole/mg/min$) than cattle (cattle, $32.8{\pm}1.2nmole/mg/min$). Interestingly, testosterone $16{\alpha}$-hydroxylase, a marker enzyme for P-450 IIA was not detected in both animal species. These results suggest that Korean native cattle and pigs have high contents of P-450 IA1 and P-450 IIIA. Total sulfhydryl compound (cattle, $10.3{\pm}1.1nmole/mg$ ; Pigs, $14.5{\pm}1.8nmole/mg$) and glutathione related enzymes except glutathione reductase (cattle, $38.1{\pm}7.9nmole/mg/min$; swine, $22{\pm}3.6nmole/mg/min$) showed higher levels in swine than in Korean native cattle. Superoxide dismutase (cattle, $7.64{\pm}0.84nmole/mg/min$ ; pigs, $4.47{\pm}0.94nmole/mg/min$) and catalase (cattle, $30.4{\pm}3.7nmole/mg/min$ ; pigs, $17.2{\pm}1.8nmole/mg/min$) were remarkably higher in Korean native cattle than in swine (p<0.05).