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Mitochondrial Mechanisms of Tubular Injury
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Rick G. Schnellmann, Richard D. Griner
In addition to these indirect probings, direct measurements of enzyme activity is a common technique to assess impairment of the tricarboxylic acid cycle enzymes or to the F0F1-ATPase. Inhibitors of specific mitochondrial functions such as atractyloside, to inhibit ADP/ATP translocase, and oligomycin are frequently used during measurements of ATPase activity and QO2. Conversely, more qualitative determinations such as morphological examinations are typically made to reveal gross changes in mitochondrial structure. Finally, the consequence of mitochondrial dysfunction, decreases in cellular ATP, and other adenine nucelotides can be determined by a variety of methods.
Primary Stress Damage of the Heart
Published in Felix Z. Meerson, Alexander V. Galkin, Adaptive Protection of The Heart: Protecting Against Stress and Ischemic Damage, 2019
Felix Z. Meerson, Alexander V. Galkin
This issue has been confirmed and developed in later studies. The most demonstrative result has been obtained by Bricknell et al.,105 who studied the role of glycolysis in the energy provision for membrane Ca2+ transport with a model of cardiac contracture developing in prolonged myocardial ischemic hypoxia. This contracture, being an energy-deficient muscle-relaxation disorder, results not from simple lack of ATP in the contractile apparatus, but precisely from the ATP-deficient interruption of the membrane pump responsible for Ca2+ removal from the myofibrillar troponin complexes.106,107 To collate the roles of the mitochondrial and the glycolytic ATP in the calcium pump function, the authors have studied the development of contracture (1) under blocked glycolysis and intact oxidative phosphorylation and mitochondrial ATP transport, and (2) under operative glycolysis and blocked mitochondrial ATP transport. The scheme in Figure 12 shows that in the first series glycolysis was switched off by removing glucose from the perfusing solution and adding glycolytic inhibitors — monoiodoacetate or deoxyglucose; simultaneously, acetate was added as a substrate to maintain oxidative phosphorylation. In the second series the glucose concentration was normal, glycolysis proceeded freely, oxidative phosphorylation also was not specially blocked, but translocation of mitochondrial ATP to the perimyofibrillar space was inhibited with atractyloside (Figure 12B).
TCM safety and regulations
Published in Raymond Cooper, Chun-Tao Che, Daniel Kam-Wah Mok, Charmaine Wing-Yee Tsang, Chinese and Botanical Medicines, 2017
Raymond Cooper, Chun-Tao Che, Daniel Kam-Wah Mok, Charmaine Wing-Yee Tsang
Fructus xanthii or Cangerzi is the dried ripe fruit and involucre of Xanthium sibiricum Patrin ex Widder (Asteraceae). It had been used in Chinese Medicine to expel wind-cold, clear the nasal passage, and expel wind and dampness. Hepatotoxicity and acute renal failure have been reported due to an overdose and prolonged usage of Cangerzi. Two hepatotoxic compounds of diterpenoid glycosides in Cangerzi have been identified as atractyloside (Figure 7.4) and carboxy-atractyloside. In the health guidelines issued by the Department of Health, HKSAR government and Chinese Pharmacopeia, it is recommended that Cangerzi should be properly processed to reduce the toxicity. This procedure requires stir-frying until yellow-brown on the surface. Studies have shown that using this process leads to a significant reduction in the amount of hepatotoxic compounds.
Himalayan poisonous plants for traditional healings and protection from viral attack: a comprehensive review
Published in Toxin Reviews, 2022
Shriya Pathania, Diksha Pathania, Priyanka Chauhan, Mamta Sharma
Respiration which occurs in mitochondria is commonly known as cellular respiration and produces ATP, is another susceptible target in animals, since for cellular and organ functions, ATP is essential. Many plant poisons can assault this objective with HCN, which ties to press particles of the terminal cytochrome oxidase in the mitochondrial respiratory chain. HCN does not usually occur in a free structure, however, is put away as Cyanogenic glucoside in plant cell vacuoles. When plants are injured, the content of the vacuoles gets into contact with enzymes, such as nitrilase and β-glucosidase due to the ruptured cellular matrix. These enzymes hydrolyze and Cyanogenic glucoside releases extremely toxic HCN. The Diterpene atractyloside is a powerful inhibitor of the mitochondrial ADP/ATP transporter and thus inhibits the ATP supply of cells (Wink 2007b).
Study on the protective effects of danshen-honghua herb pair (DHHP) on myocardial ischaemia/reperfusion injury (MIRI) and potential mechanisms based on apoptosis and mitochondria
Published in Pharmaceutical Biology, 2021
Jiqing Bai, Xiaoping Wang, Shaobing Du, Pengfei Wang, Yaheng Wang, Lina Quan, Yundong Xie
Radio-immunoprecipitation assay (RIPA), phenylmethyl sulphonyl fluoride (PMSF), enhanced BCA protein assay kit, SDS-PAGE gel electrophoresis buffer, beyoecl star reagent and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) apoptosis assay kit bought from Beyotime Institute of Biotechnology (Shanghai, China). 2,3,5-Triphenyltetrazolium chloride (TTC) was bought from Wanleibio (Wuhan, China). Atractyloside (ATR; purity: ≥98%) were purchased from Shang Hai Pure One Biotechnology (Shanghai, China). ATR powder was dissolved in normal saline to inject intraperitoneally for the animal experiment. ATR powder was dissolved in DMEM/F12 medium (BOSTER Biological Technology Co. Ltd) for the cell experiments. The material for the Western blots that Cytochrome C antibody (WL02410), Bax antibody (WL01637), Bcl-2 antibody (WL01556), caspase-3/cleaved-caspase-3 antibody (WL02117), caspase-9/cleaved-caspase-9 antibody (WL03421), the secondary antibody goat anti-rabbit IgG-HRP (WLA023) and internal reference antibody GAPDH (WL01114) were bought from Wanleibio (Wuhan, China). XNT were purchased from Junbisazza Pharmaceutical Limited Company (Lot: 20181225).
Acute toxic kidney injury
Published in Renal Failure, 2019
Nadezda Petejova, Arnost Martinek, Josef Zadrazil, Vladimir Teplan
The mechanism by which C. laureola and thistle Atractylis gummifera induce nephrotoxicity is not completely known. However, the basic nephrotoxin in these herbal remedies has been identified as a diterpene glycoside – atractyloside, which in animal studies has been found to affect renal cortical mitochondria and proximal tubular fragments. There is evidence that the nephrotoxicity may be caused by altered mitochondrial respiration and inhibition of oxygen uptake by the intact cells [58].