Glutathione membrane potential

As a rule, oxygen radical overproduction in mitochondria is accompanied by peroxidation of mitochondrial lipids, glutathione depletion, and an increase in other parameters of oxidative stress. Thus, the enhancement of superoxide production in bovine heart submitochondrial particles by antimycin resulted in a decrease in the activity of cytochrome c oxidase through the peroxidation of cardiolipin [45]. Iron overload also induced lipid peroxidation and a decrease in mitochondrial membrane potential in rat liver mitochondria [46]. Sensi et al. [47] demonstrated that zinc influx induced mitochondrial superoxide production in postsynaptic neurons. 

Klein, M. et al., A membrane-potential dependant ABC-like transporter mediates the vacuolar uptake of rye flavone glucuronides regulation of glucuronide uptake by glutathione and its conjugates. Plant J., 21, 289, 2000. 

Bajijiasu. Chen et al. [248] studied the protective effect ofBajijiasu (P-D-fructofuranosyl (2-2) p-D-fructofuranosyl), a dimeric fructose isolated from the Chinese herb radix Morinda officinalis, on Ap-induced neurotoxicity in pheochromocytoma (PC12) cells. Bajijiasu reversed the reduction in cell viability induced by exposure to Ap25 35, reduced Ap25 35-induced toxicity, decreased the accumulation of intracellular ROS and the lipid peroxidation product malondialdehyde, upregulated expression of glutathione reductase and superoxide dismutase, prevented depolarization of the mitochondrial membrane potential ( Em), and blocked... 

The result is redox cycling which produces active oxygen species which can deplete NADPH and glutathione and potentially cause peroxidation of membrane lipids. 

Assays that measure mitochondrial function and cell viability and growth, cell membrane integrity, membrane potential, intracellular ATP, reduced glutathione... 

McLean and coworkers have reported that inhibitors of MPT (cyclosporine A and trifluoperazine) inhibited acetaminophen toxicity in rat liver slices and in vivo when administered as a cocktail with fructose (Beales and McLean 1996 Nieminen et al. 1997). Also, Dimova et al. (1995) reported that the MPT inhibitor trifluoperazine decreased acetaminophen-induced hepatotoxicity in the mouse. Masubuchi et al. (2005) reported that Cyclosporine A decreased acetaminophen toxicity in mice. Since hepatic glutathione depletion was the same in acetaminophen-treated and acetaminophen plus cyclosporine A-treated mice, it was concluded that the decrease in toxicity was not mediated by inhibition of NAPQI formation. Moreover, they observed that acetaminophen caused a swelling of liver mitochondria and a decrease in mitochondrial membrane potential, both of which were elinrinated by cotreatment with Cyclosporine A. Collectively, the data indicate that MPT is an important mechanism leading to acetaminophen toxicity. 

Figure 9 Handling of 6-PG in renal proximal tubular cells. Abbreviations BBM, brush border plasma membrane BLM, basolateral plasma membrane 6-MP, 6-mercaptopurine 6-PG, S-(6-purinyl) glutathione 6-PC, S-(6-purinyl)-L-cysteine NAcPC, w-acetyl-S-(6-purinyl)-L-cysteine GGT, y-glutamyltransferase DP, dipeptidase P-lyase, cysteine conjugate P-lyase PLP, pyridoxal phosphate XO, xanthine oxidase 6-ThXan, 6-thioxanthine 6-ThUrate, 6-thiourate AOAA, aminooxyacetic acid and Av /, membrane potential. (Adapted from Ref. 30.)...

Tong, V. Teng, X. W Chang, T. K. H. Abbott, F. S. Valproic acid II effects on oxidative stress, mitochondrial membrane potential, and cytotoxicity in glutathione-depleted rat hepatocytes. Toxicol. Sci. 2005, 86, 436-443. 

Silver NPs (15 and lOOnm) were evaluated for their potential toxicity in vitro in BRL 3A rat liver cells [10], In order to evaluate such toxicity, the cellular morphology, mitochondrial function MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, membrane leakage of lactate dehydrogenase (LDH), reduced glutathione (GSH) levels, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were assessed during a 24-h exposure period. 

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