scholarly journals F1F0-ATPase, early target of the radical initiator 2,2′-azobis-(2-amidinopropane) dihydrochloride in rat liver mitochondria in vitro

1996 ◽  
Vol 320 (2) ◽  
pp. 571-576 ◽  
Author(s):  
Frédéric BEAUSEIGNEUR ◽  
Marc GOUBERN ◽  
Marie-France CHAPEY ◽  
Joseph GRESTI ◽  
Catherine VERGELY ◽  
...  
Keyword(s):  
Permeability Transition ◽  
Liver Mitochondria ◽  
Proton Channel ◽  
Rat Liver Mitochondria ◽  
Antioxidant Defences ◽  
Radical Initiator ◽  
Malondialdehyde Formation ◽  
Respiratory Chain Activity ◽  
F1fo Atpase

This study was designed to determine which enzyme activities were first impaired in mitochondria exposed to 2,2′-azobis-(2-amidinopropane) dihydrochloride (AAPH), a known radical initiator. EPR spin-trapping revealed generation of reactive oxygen species although malondialdehyde formation remained very low. With increasing AAPH concentrations, State-3 respiration was progressively depressed with unaltered ADP/O ratios. A top-down approach demonstrated that alterations were located at the phosphorylation level. As shown by inhibitor titrations, ATP/ADP translocase activity was unaffected in the range of AAPH concentrations used. In contrast, AAPH appeared to exert a deleterious effect at the level of F1FO-ATPase, comparable with dicyclohexylcarbodi-imide, which alters FO proton channel. A comparison of ATP hydrolase activity in uncoupled and broken mitochondria reinforced this finding. In spite of its pro-oxidant properties, AAPH was shown to act as a dose-dependent inhibitor of cyclosporin-sensitive permeability transition initiated by Ca2+, probably as a consequence of its effect on F1FO-ATPase. Resveratrol, a potent antiperoxidant, completely failed to prevent the decrease in State-3 respiration caused by AAPH. The data suggest that AAPH, when used under mild conditions, acted as a radical initiator and was capable of damaging F1FO-ATPase, thereby slowing respiratory chain activity and reducing mitochondrial antioxidant defences.

scholarly journals Chenodeoxycholate Is a Potent Inducer of the Permeability Transition Pore in Rat Liver Mitochondria

2001 ◽  
Vol 21 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Anabela P. Rolo ◽  
Paulo J. Oliveira ◽  
António J. M. Moreno ◽  
Carlos M. Palmeira
Keyword(s):  
Bile Acids ◽  
Rat Liver ◽  
Cell Injury ◽  
Disease Process ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Potent Inducer

Several reports support the concept that bile acids may be cytotoxic during cholestatic disease process by causing mitochondrial dysfunction. Here we report additional data and findings aimed at a better understanding of the involvement of the permeability transition pore (PTP) opening in bile acids toxicity. The mitochondrial PTP is implicated as a mediator of cell injury and death in many situations. In the presence of calcium and phosphate, chenodeoxycholic acid (CDCA) induced a permeability transition in freshly isolated rat liver mitochondria, characterized by membrane depolarization, release of matrix calcium, and osmotic swelling. All these events were blocked by cyclosporine A (CyA) and the calcium uniporter inhibitor ruthenium red (RR). The results suggest that CDCA increases the sensitivity of isolated mitochondria in vitro to the calcium-dependent induction of the PTP.

scholarly journals Polarographic and spectroscopic studies of the effects of fluoroacetate/fluorocitrate on cells and mitochondria

2007 ◽  
Vol 21 (2) ◽  
pp. 121-134 ◽  
Author(s):  
Valeriy P. Zinchenko ◽  
Nikolay V. Goncharov ◽  
Vera V. Teplova ◽  
Vitaliy A. Kasymov ◽  
Olga I. Petrova ◽  
...  
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Spectroscopic Studies ◽  
Reciprocal Relationship ◽  
Rat Liver Mitochondria ◽  
Calcium Balance ◽  
Pyridine Nucleotides

Experiments were performed with rat liver mitochondria, Ehrlich ascite tumor cells (EATC) and cardiomyocytes, exposed to fluoroacetate (FA) or fluorocitrate (FC)in vitro. The effects of FA developed at much higher concentrations in comparison with FC and was dependent upon respiratory substrates: with pyruvate, FA induced a slow oxidation of pyridine nucleotides (NAD(P)H) and inhibition of respiration. NAD(P)H oxidation was prevented by incubation of mitochondria with cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore. Studies of the NAD(P)H level and calcium response generated in EATC under activation with ATPviathe metabotropic P2Y receptor, revealed a loss of NAD(P)H from mitochondria resulting in a shift in the balance of mitochondrial and cytosolic NAD(P)H on exposure to FA. An increase of cytosolic [Ca2+] was observed in the cell lines exposed to FA and is explained by activation of plasma membrane calcium channels; this mechanism could have an impact on amplitude and rate of Ca2+waves in cardiomyocytes, and cause the hypersensitivity of platelets reported on earlier. Highlighting the reciprocal relationship between intracellular NAD(P)H and calcium balance, we discuss metabolic pathway modulation in the context of development of an effective therapy for FA poisoning.

Magnetic nanostructured lipid carrier for dual triggered curcumin delivery: Preparation, characterization and toxicity evaluation on isolated rat liver mitochondria

2021 ◽  
pp. 088532822110346
Author(s):  
Mohammad Yoozbashi ◽  
Hamid Rashidzadeh ◽  
Mehraneh Kermanian ◽  
Somayeh Sadighian ◽  
Mir-Jamal Hosseini ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Nanostructured Lipid Carrier ◽  
Mitochondrial Toxicity ◽  
X Ray Diffraction ◽  
Temperature Dependent ◽  
Reducing Ability ◽  
Transmission Electron

In this research, magnetic nanostructured lipid carriers (Mag-NLCs) were synthesized for curcumin (CUR) delivery. NLCs are drug-delivery systems prepared by mixing solid and liquid (oil) lipids. For preparation of NLCs, cetylpalmitate was selected as solid lipid and fish oil as liquid lipid. CUR-Mag-NLCs were prepared using high-pressure homogenization technique and were characterized by methods including X-ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), and dynamic light scattering (DLS). The CUR-Mag-NLCs were developed as a particle with a size of 140 ± 3.6 nm, a polydispersity index of 0.196, and a zeta potential of −22.6 mV. VSM analysis showed that the CUR-Mag-NLCs have excellent magnetic properties. Release rate of the drug was higher at 42 °C than 37 °C, indicating that release of the synthesized nanoparticles is temperature-dependent. Evaluation of mitochondrial toxicity was done using the isolated rats liver mitochondria including glutathione (GSH), malondialdehyde (MDA), and the ferric- reducing ability of plasma (FRAP) assays to study biosafety of the CUR-Mag-NLCs. Results of In vitro study on the isolated mitochondria revealed that both CUR-Mag-NLCs and curcumin have no specific mitochondrial toxicity.

IN VITRO LIPID PEROXIDATION INHIBITORY AND ANTI-ARTHRITIC ACTIVITIES OF SOME INDIAN MEDICINAL PLANTS

INDIAN DRUGS ◽  
2012 ◽  
Vol 49 (06) ◽  
pp. 31-35
Author(s):  
A. A Rege ◽  
◽  
P. R. Juvekar ◽  
A. R. Juvekar
Keyword(s):  
Lipid Peroxidation ◽  
Liver Mitochondria ◽  
Tinospora Cordifolia ◽  
Ocimum Sanctum ◽  
Rat Liver Mitochondria ◽  
Total Phenolic ◽  
Lipid Peroxidation Inhibitory Activity ◽  
Gallic Acid Equivalent ◽  
Indian Medicinal Plants

Anti-lipid peroxidation effect of aqueous extracts of Ocimum sanctum, Tinospora cordifolia and Withania somnifera was evaluated against Fe2+-ascorbic acid-induced lipid peroxidation using rat liver mitochondria as model system, whereas, anti-arthritic activity was evaluated by proteinase inhibitory assay. O. sanctum showed potent anti-lipid peroxidation and anti-arthritic activities. T. cordifolia exhibited moderate anti-lipid peroxidation activity, but considerable anti-arthritic activity, whereas, W. somnifera revealed least lipid peroxidation inhibitory activity and considerable anti-arthritic activity. Besides, Folin-Ciocalteu reagent in terms of gallic acid equivalent achieved the total phenolic content and the trend was found to be O. sanctum > T. cordifolia > W. somnifera.

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