• Toxicological Research
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• 제35권1호
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• pp.13-24
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• 2019

Numerous ethnomedicinal uses have been attributed to different parts of Annona senegalensis (ASE), including its uses as food and food additives. The present study investigated toxicological and antioxidant effects of 28 days administration of ethanol extracts of ASE stem bark to Wistar strain albino rats. Acute toxicity test was done to determine lethal dose in Wistar rats while sub-acute toxicity test was conducted on rats divided into four groups (A - control, B - 50 mg/kg, C - 100 mg/kg, D - 150 mg/kg, respectively and treated for 28 days. Oxidative stress markers in liver and kidney as well as hepatic succinate dehydrogenase activity in the mitochondrial and post mitochondrial fractions (PMF) were evaluated. The $LD_{50}$ value of ASE was > 2,000 mg/kg. White blood cell counts gradually increased, but red blood cell counts and haematocrits level decreased significantly (p < 0.05) by about 50%. Liver enzymes in the serum and mitochondrial succinate dehydrogenase activity increased significantly (p < 0.05). Superoxide dismutase and catalase activities also increased in liver mitochondria and PMF while malondialdehyde (MDA) and reduced glutathione levels increased only in the PMF. Furthermore, only MDA levels increased significantly in the kidney after 28 days extract administration. Histopathological examination showed hepatic necrosis and no obvious signs of nephrotoxicity. Anona senegalensis is relatively safe, but prolonged ingestion could induce oxidative stress and impair ATP synthesis through the modulation of the activity of mitochondrial succinate dehydrogenase.

• 한국환경농학회지
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• 제6권2호
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• pp.94-100
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• 1987

미토콘드리아는 가시광선의 조사에 의해 그 고유한 생화학적 기능에 저해를 받게 되며 그것은 주로 파장 영역 $350{\sim}500nm$의 청색광이 유발하는 광역학적 작용(photodynamic action)의 결과라는 가정을 입증하는 자료를 수집하였다. 미토콘드리아막에 결합되어 있는 전자전달계효소들 중에서 NADH dehydrogenase, succinate dehydrogenase, 및 cytochrome c oxidase의 광저해(photoinhibition)를 조사하였던 바, 모든 효소들이 청색광에 의해 상대적으로 심한 활성상실을 보였다. NADH dehydrogenase의 FMN과 cytochrome c oxidase의 heme group은 산소가 관여하는 photosensitizer(photodynamic sensitizer)임에 반해, succinate dehydrogenase의 FAD는 sensitizer로서의 기능을 보이지 않는 대신 Fe-S center가 산소와 무관한 photosensitizer일 것이라고 해석되었다. heme group에 들어 있는 Fe도 역시 산소와 무관한 광화학반응에 어느 정도 기여하리라고 추정되는 결과도 얻었다. 미토콘드리아 전체로 볼 때 생리적 활성저해에 가장 크게 기여하는 가시광은 산소존재 조건하의 청색광이였고, 그 저해기작에는 active oxygens가 관여되어 있다는 것을 $O_2$의 분석을 통해 확인하였다. 한편 active oxygens의 생성은 미토콘드리아막의 과산화를 초래하였으며, 역시 청색광/$O_2$조건에서 그 정도가 가장 심하였다.

• Korean Journal of Acupuncture
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• 제37권1호
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• pp.37-45
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• 2020

Objectives : Mitochondria are typically known as intracellular double membrane-bound structures that supply energy for intracellular metabolism including Krebs cycle and beta-oxidation. Also, acupuncture has been known to stimulate the flow of energy. To explore the effect of acupuncture on the mitochondrial respiratory chain activities in rat's heart and kidneys, the activities of mitochondrial respiratory chain complexes I to IV were observed. Methods : The rats were divided into 11 groups; Normal (no acupuncture treatment and under anesthesia for 10 min), heart meridian five-transport-points (acupuncture treatment at HT9, HT8, HT7, HT4 and HT3 under anesthesia for 10 min), and kidney meridian five-transport-points (acupuncture treatment at KI1, KI2, KI3, KI7 and KI10 under anesthesia for 10 min). All rats were sacrificed and the heart and kidneys were examined for the changes of respiratory chain activities. Results : Acupuncture at HT7 increased the activity of succinate dehydrogenase; acupuncture at KI2 increased the activity of ubiquinol cytochrome C oxidoreductase; and acupuncture at HT9, HT8, HT3 and KI1 increased activities of cytochrome C oxidase. Conclusions : Acupuncture assists mitochondrial repiratory chain activity via the Cytochrome C oxidase signaling pathway in heart and kidney of rats.

• 대한약리학회지
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• 제21권1호
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• pp.12-26
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• 1985

흰쥐 뇌 미토콘드리아에 의한 $O^{-}_{2}{\cdot}$ 의 생성과 이 radical의 유해작용 및 그 작용기전을 알아보기 위하여 본실험을 수행하였다. Succinate와 antimycin존재하에서 미토콘드리아는 $O^{-}_{2}{\cdot}$을 생성하였으며 이는 SOD-inhibitable NBT환원으로 확인되었다. 동일 조건에서 $H_2O_2$는 일차생성물인 $O^{-}_{2}{\cdot}$의 dismutation으로 생성됨을 알수 있었다. 상기조건에서 미토콘드리아의 막지질이 파괴되었고 반응액에 첨가된 isocitrate dehydrogenase와 적혈구에 각각 불활성화와 용혈이 초래되었다. 이같은 작용은 $Fe^{++}$이 있을때만 관찰 되었다. 그리고 독작용은 superoxide dismutase 혹은 castalase에 의해서 억제되었다. 또한 methional을 첨가하였을 때 ethylene이 생성되었으며 그 생성은 $Fe^{++}$에 의하여 현저히 증가하였다. Ethylene 생성 역시 상기 효소에 의하여 억제되었다. 따라서 미토콘드리아에서 발생된 $O^{-}_{2}{\cdot}$은 거대분자 및 세포에 독성을 나타낼수 있으며 이같은 작용은 $Fe^{++}$의 촉매작용에 의한 $O^{-}_{2}{\cdot}$와 $H_2O_2$의 상호작용으로 발생되는 $OH{\cdot}$ 에 의한것으로 추측되었다. 이상의 결과는 미토콘드리아가 유독성 산소 radical을 발생하므로 조직손상을 시킬 수 있다는 가능성을 시사하는 증거라고 생각되었다.

• Korean Journal of Acupuncture
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• 제36권4호
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• pp.200-209
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• 2019

Objectives : The liver is rich in mitochondria and it plays a key role in whole-body energy homeostasis. Mitochondria is double membrane-bound organelle that supplies energy for intracellular metabolism including Krebs cycle and beta-oxidation. Acupuncture is known to stimulate and regulate the flow of energy. To explore the effect of acupuncture on the mitochondrial respiratory chain activity in the rats' livers, the activity of mitochondrial respiratory chain complexes I to IV was observed. Methods : The rats were divided into 4 groups; Normal 1 (no acupuncture treatment and anesthesia for 5 min), Normal 2 (no acupuncture treatment and anesthesia for 10 min), MA1 (acupuncture treatment at bilateral LR3 under anesthesia for 5 min), and MA2 (acupuncture treatment at bilateral LR3 under anesthesia for 10 min). All rats were sacrificed and the livers were examined for respiratory chain change. Results : There was no difference in ubiquinon oxidoreductase, succinate dehydrogenase, and ubiquinol cytochrome C oxidoreductase after acupuncture at LR3. Acupuncture at LR3 for 10 min increased the activity of cytochrome C oxidase compared with no acupuncture groups. Conclusions : Acupuncture at LR3 mediated mitochondrial respiratory chain activity via the cytochrome C oxidase signaling pathway in the livers of rats.

• Molecules and Cells
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• 제38권12호
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• pp.1054-1063
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• 2015

Mitochondria play a crucial role in eukaryotic cells; the mitochondrial electron transport chain (ETC) generates adenosine triphosphate (ATP), which serves as an energy source for numerous critical cellular activities. However, the ETC also generates deleterious reactive oxygen species (ROS) as a natural byproduct of oxidative phosphorylation. ROS are considered the major cause of aging because they damage proteins, lipids, and DNA by oxidation. We analyzed the chronological life span, growth phenotype, mitochondrial membrane potential (MMP), and intracellular ATP and mitochondrial superoxide levels of 33 single ETC component-deleted strains during the chronological aging process. Among the ETC mutant strains, 14 ($sdh1{\Delta}$, $sdh2{\Delta}$, $sdh4{\Delta}$, $cor1{\Delta}$, $cyt1{\Delta}$, $qcr7{\Delta}$, $qcr8{\Delta}$, $rip1{\Delta}$, $cox6{\Delta}$, $cox7{\Delta}$, $cox9{\Delta}$, $atp4{\Delta}$, $atp7{\Delta}$, and $atp17{\Delta}$) showed a significantly shorter life span. The deleted genes encode important elements of the ETC components succinate dehydrogenase (complex II) and cytochrome c oxidase (complex IV), and some of the deletions lead to structural instability of the membrane-$F_1F_0$-ATP synthase due to mutations in the stator stalk (complex V). These short-lived strains generated higher superoxide levels and produced lower ATP levels without alteration of MMP. In summary, ETC mutations decreased the life span of yeast due to impaired mitochondrial efficiency.

• International Journal of Oral Biology
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• 제34권4호
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• pp.185-190
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• 2009

This study examined the effects of red light generated from a light emitting diode (LED) upon proliferation and mitochondrial stress in human gingival fibroblasts (hGFs). Cells were exposed to LED-generated red light at a clinically relevant intensity and distance with a 610-630 nm wavelength for various times (0-48 min). At different exposure times, cells were processed for the analysis of succinate dehydrogenase (SDH) activity, proliferation, mitochondrial membrane potential (MMP) and cytotoxicity. Cell cycle progression was also investigated by flow cytometry after staining with propidium iodide. Red light exposure was found to inhibit SDH activity and DNA synthesis in hGFs in a time-dependent manner. Light exposure also reduced the MMP levels in these cells and this was closely associated with a $G_0/G_1$ arrest. In contrast, exposure of hGFs to red light for 48 min led to a dramatic loss of MMP with an attendant increase in cytotoxicity. These findings demonstrate that LED-generated red light may cause mitochondrial stress and growth inhibition in hGFs during tooth whitening therapy, depending on the length of the exposure.