Involvement of nitroxide radicals in cocaine-induced hepatotoxicity

1982 ◽  
Vol 60 (12) ◽  
pp. 1614-1620 ◽  
Author(s):  
Elmer J Rauckman ◽  
Michelle W Kloss ◽  
Gerald M Rosen
Keyword(s):  
Hydrogen Peroxide ◽  
Reduced Glutathione ◽  
Cellular Proteins ◽  
Lipid Hydroperoxides ◽  
Pyridine Nucleotides ◽  
Futile Cycle ◽  
The One ◽  
Cytochrome P 450 ◽  
Stimulation Of

Cocaine administration can produce hepatotoxicity in non-induced mice of at least one strain, DBA/2Ha and hepatotoxicity in induced mice of several strains. Metabolic studies and the administration of metabolites indicate that the minor metabolic pathway, cocaine → norcocaine → N-hydroxynorcocaine → norcocaine nitroxide, is responsible for the observed cocaine-induced hepatotoxicity. In vitro experiments show that cytochrome P-450 can oxidize N-hydroxynorcocaine to norcocaine nitroxide. Norcocaine nitroxide is unreactive towards cellular proteins or glutathione but does react directly with reduced pyridine nucleotides and is rapidly reduced enzymatically by the microsomal flavoproteins, NADPH-cytochrome P-450 reductase and FAD-containing monooxygenase. These reactions constitute a futile cycle in which NADPH is consumed and superoxide and hydrogen peroxide are generated. We postulate that the destruction of hydrogen peroxide by glutathione peroxidase results in the accumulation of excess oxidized glutathione which is actively excreted by the cell, since insufficient NADPH is available for glutathione reductase to maintain the GSH/GSSG ratio at an acceptable level. As reduced glutathione levels diminish, the cell can no longer protect itself against toxic lipid hydroperoxides which accumulate as a result of stimulation of lipid peroxidation (caused by the one electron cycling reaction, N-hydroxynorcocaine to norcocaine nitroxide cycle). Finally, as glutathione is depleted below a certain level, the cell loses the ability to maintain the GSH/GSSG ratio in a range consistent with homeostasis resulting in loss of cellular function. Ultimately, necrosis results. This mechanism is consistent with all the information available concerning cocaine-induced hepatotoxicity.

Stimulation of in vitro angiogenesis by hydrogen peroxide and the relation with Ets-1 in endothelial cells

Life Sciences ◽  
1998 ◽  
Vol 64 (4) ◽  
pp. 249-258 ◽  
Author(s):  
Masako Yasuda ◽  
Yumi Ohzeki ◽  
Shunichi Shimizu ◽  
Shinji Naito ◽  
Akira Ohtsuru ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Endothelial Cells ◽  
In Vitro Angiogenesis ◽  
Stimulation Of

scholarly journals Stimulation of Root Formation by Thiol Compounds

HortScience ◽  
1996 ◽  
Vol 31 (2) ◽  
pp. 240-243 ◽  
Author(s):  
Guy Auderset ◽  
Charles Moncousin ◽  
Jane O'Rourke ◽  
D. James Morré
Keyword(s):  
Acetic Acid ◽  
Glycine Max ◽  
Root Formation ◽  
Reduced Glutathione ◽  
Root Primordia ◽  
Hedera Helix ◽  
Thiol Compounds ◽  
Indole 3 Acetic Acid ◽  
Stimulation Of

Root formation in shoot cuttings of soybean (Glycine max L. `Williams'), mungbean (Phaseolus aureas Mdlbg.), English ivy (Hedera helix L.), and apple (Malus ×domestica Borkh. `Jork 9') was stimulated by dithiothreitol and reduced glutathione in the presence and absence of auxin (IAA) shock. In soybean, in the absence of auxin, root formation was stimulated to about the same extent by glutathione alone as with auxin alone. The roots induced by thiol compounds were longer than roots induced by auxin shock and were completely normal in appearance. Roots produced with auxin shock alone were short and exhibited characteristic auxin-induced deformations. With a combination treatment of auxin shock and thiol compounds, roots were more numerous than with either alone, somewhat longer than with auxin alone, and exhibited fewer of the usual deformations characteristic of roots grown in the presence of external auxins. The thiol compounds also were beneficial for rooting Malus shoots propagated from callus in vitro. The thiol compounds were most beneficial with older cuttings where auxin shock was often insufficient to obtain roots. In shoots where rooting was stimulated by thiol agents, shoots grew more rapidly than in those where rooting was induced by auxin shock alone. These findings suggest a use for thiol compounds alone or in combination with auxin shock to induce differentiation of root primordia as well as for stimulation of root growth. Chemical name used: indole-3-acetic acid (IAA).

Hydrogen peroxide induces endothelium-dependent and -independent coronary arteriolar dilation: role of cyclooxygenase and potassium channels

2003 ◽  
Vol 285 (6) ◽  
pp. H2255-H2263 ◽  
Author(s):  
Naris Thengchaisri ◽  
Lih Kuo
Keyword(s):  
Hydrogen Peroxide ◽  
Smooth Muscle ◽  
Potassium Channels ◽  
Prostaglandin E ◽  
Inward Rectifier Potassium Channels ◽  
Cytochrome P 450 ◽  
Cox 1 ◽  
Coronary Arterioles

Hydrogen peroxide, a relatively stable reactive oxygen species, is known to elicit vasodilation, but its underlying mechanism remains elusive. Here, we examined the role of endothelial nitric oxide (NO), prostaglandin, cytochrome P-450-derived metabolites, and smooth muscle potassium channels in coronary arteriolar dilation to abluminal H2O2. Pig subepicardial coronary arterioles (50–100 μm) were isolated and pressurized without flow for in vitro study. Arterioles developed basal tone and dilated dose dependently to H2O2 (1–100 μM). Disruption of th endothelium and inhibition of cyclooxygenase (COX) by indomethacin produced identical attenuation of vasodilation to H2O2. Conversely, the vasodilation to H2O2 was not affected by either the NO synthase inhibitor NG-nitro-l-arginine methyl ester or the cytochrome P-450 enzyme blocker miconazole. Inhibition of the COX-1, but not the COX-2 pathway, attenuated H2O2-induced dilation similarly to indomethacin. The production of prostaglandin E2 (PGE2), but not prostaglandin I2, from coronary arterioles was significantly increased by H2O2. Furthermore, inhibition of PGE2 receptors with AH-6809 attenuated vasodilation to H2O2 similar to that produced by indomethacin. In the absence of a functional endothelium, H2O2-induced dilation was attenuated, in an identical manner, by a depolarizing agent KCl and a calcium-activated potassium (KCa) channel inhibitor iberiotoxin. However, PGE2-induced dilation was not affected by iberiotoxin. The endothelium-independent dilation to H2O2 was also insensitive to the inhibition of guanylyl cyclase, lipoxygenase, ATP-sensitive potassium channels, and inward rectifier potassium channels. These results suggest that H2O2 induces endothelium-dependent vasodilation through COX-1-mediated release of PGE2 and also directly relaxes smooth muscle by hyperpolarization through KCa channel activation.

Inhibition of nitric oxide synthesis improves detoxication in inflammatory liver dysfunction in vivo

1997 ◽  
Vol 273 (2) ◽  
pp. G530-G536 ◽  
Author(s):  
A. Veihelmann ◽  
T. Brill ◽  
M. Blobner ◽  
I. Scheller ◽  
B. Mayer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
In Vitro Assays ◽  
Serum Concentrations ◽  
Aminopyrine Breath Test ◽  
Vitro Assay ◽  
Synthase Inhibitor ◽  
Cytochrome P 450 ◽  
Stimulation Of

Inflammatory stimulation of the liver induces nitric oxide (NO) biosynthesis and suppression of detoxication. In this study the effect of NO biosynthesis on cytochrome P-450 (CYP) enzyme activity was investigated by comparing in vivo and in vitro assays. To establish liver inflammation, CD rats were injected with Corynebacterium parvum (C. parvum) suspension. After 5 days NO biosynthesis was highly induced as indicated by increased NO2- plus NO3- serum concentrations. At the same time the aminopyrine breath test (ABT), measuring CYP activity in vivo, was reduced to 42% and the in vitro assay of aminopyrine turnover was suppressed to 12% of NaCl- injected controls. When C. parvum-injected animals were treated with the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA), CYP activities significantly improved with an ABT of 76% and an in vitro aminopyrine turnover of 47% of controls. Neither C. parvum injections nor L-NMMA treatment resulted in a significant change of CYP protein concentrations. These data indicate that suppression of xenobiotic metabolism can be attenuated by inhibition of NO biosynthesis during an ongoing process of inflammation.

Influence of thiol substances on in vitro and in vivoL-thyroxine deiodination in rainbow trout, Salmo gairdneri

1984 ◽  
Vol 62 (8) ◽  
pp. 1495-1501 ◽  
Author(s):  
J. G. Eales ◽  
Shirley Shostak ◽  
Catherine G. Flood
Keyword(s):  
Rainbow Trout ◽  
Reduced Glutathione ◽  
Salmo Gairdneri ◽  
Physiological Conditions ◽  
Low Concentrations ◽  
Dtt Dithiothreitol ◽  
High Concentrations ◽  
Stimulation Of

The effects of the thiols DTT (dithiothreitol) and GSH (reduced glutathione) on hepatic in vitro and in vivo T4 (L-thyroxine) deiodination by rainbow trout held at 11 °C were studied. Hepatic deiodination increased progressively over the DTT range of 0.02–20 mM. GSH was less potent than DTT at low concentrations and strongly inhibited deiodination at high concentrations (> 1 mM). Hepatic deiodination was not increased by 1 mM NADPH or anaerobic conditions and was enhanced and not inhibited by the GSH inhibitor, diamide (2.5 mM), indicating that the low T4 deiodination in the absence of DTT is not due to endogenous GSH deficiency. Intraperitoneally injected GSH consistently increased plasma levels of 125I and [125I]-3,5,3′-triiodo-L-thyronine (T3) in fed or starved [125I]T4-injected trout, suggesting a GSH stimulation of extrahepatic T4 deiodination. However, injected GSH did not elevate plasma T3 concentrations. This was probably due to a demonstrated GSH stimulation of plasma T4 and T3 clearance. Force-fed GSH did not increase [125I]T4 deiodination. It is concluded that exogenous thiols can enhance T4 deiodination both in vitro and in vivo. However, availability of neither endogenous nor dietary GSH appears to regulate T4 deiodination under physiological conditions, including altered nutritional state.

scholarly journals Differences in the tooth whitening effect between strawberry juice and apple juice in-vitro

2012 ◽  
Vol 24 (1) ◽  
Author(s):  
Stephanie Stephanie ◽  
Ayu Trisna Hayati ◽  
Endang Sukartini
Keyword(s):  
Hydrogen Peroxide ◽  
Apple Juice ◽  
Mineral Water ◽  
Test Results ◽  
Tooth Whitening ◽  
Group Iii ◽  
The One ◽  
One Way Anova ◽  
Strawberry Juice

Bleaching is the tooth whitening by applying chemical materials oxidizing the organic tooth pigmentation and creating smaller and lighter molecules. Commonly used in the tooth bleaching is hydrogen peroxide. Strawberry and apple contain hydrogen peroxide and ellagic acid which will bond with an unsaturated bond of the tooth pigmentation. The purpose of this research was to finding out and measuring the tooth whitening level and effectivity between the strawberry and apple juice. The type of this research was a true experimental (in-vitro), using 30 samples of maxillary premolars with cutted radicular until the CEJ. Samples were divided into 3 groups (immersed in strawberry juice; apple juice; and mineral water); with three times daily immersion in one week. The tooth colour level was measured using a spectrophotometer. Data were analyzed using the one-way ANOVA and LSD test. The results showed significant differences among all groups. Normality test showed the variance between homogenous groups, with the p-value of 0.198 (p ≥ 0.05). The one-way ANOVA test results showed a significance value (0.000), indicated a significant degree of the tooth whitening level between all groups. The LSD test results showed that the tooth whitening level in group I (immersed in strawberry juice) was significantly different to group II (immersed in apple juice) and group III (immersed in mineral water), with a significance value of 0.01 and 0.00 ( p ≤ 0.05). The tooth whitening level in group II was significantly different from group III, with a significance value of 0.03 (p ≤ 0.05). There were differences in the tooth whitening level between immersion in strawberry juice, apple juice, and mineral water, with the most effective tooth whitening level found in the strawberry juice immersion.

scholarly journals Caloric Restriction Mimetics Attenuate the Hallmarks of Aging

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 512-512
Author(s):  
Guido Kroemer
Keyword(s):  
Caloric Restriction ◽  
Cellular Proteins ◽  
Nutrient Depletion ◽  
Acetyl Coenzyme A ◽  
Cellular Effects ◽  
High Throughput Technology ◽  
Screening Assays ◽  
Cancer Immunosurveillance ◽  
Stimulation Of

Abstract Nutrient depletion, which is one of the physiological triggers of autophagy, results in the depletion of intracellular acetyl coenzyme A (AcCoA) coupled to the deacetylation of cellular proteins. We found that there are at least 4 possibilities to mimic these effects, namely (i) the depletion of cytosolic AcCoA by interfering with its biosynthesis, (ii) the stimulation cytosolic AcCoA consumption, (iii) the inhibition of protein acetyltransferases, or (iii) the stimulation of protein deacetylases. Thus, AcCoA depleting agents, AcCoA-consuming agents, acetyltransferase inhibitors or deacetylase activators are highly efficient inducers of autophagy and reduce aging-associated diseases including diabetes, obesity, cardiac failure and failing cancer immunosurveillance. Hence, we classify them as “caloric restriction mimetics” (CRM). We have initiated the systematic search for CRMs based on their cellular effects in vitro. We built screening assays amenable to high-throughput technology for the identification of CRMs. These results will be discussed.

Involvement of hydrogen and lipid peroxides in acute tobacco smoking-induced platelet hyperactivity

1995 ◽  
Vol 268 (2) ◽  
pp. H679-H685 ◽  
Author(s):  
D. Blache
Keyword(s):  
Reduced Glutathione ◽  
Plasma Concentrations ◽  
Lipid Peroxides ◽  
Thiobarbituric Acid ◽  
Thiobarbituric Acid Reactive Substance ◽  
Lipid Hydroperoxides ◽  
Platelet Activity ◽  
Induced Aggregation ◽  
Platelet Hyperaggregability

Previous studies have established that cigarette smoking results in acute platelet hyperaggregability. We investigated whether changes in plasma oxidative properties could occur after smoking and whether such changes could be responsible for this enhanced platelet activity. In the present work, we report that platelets from nonsmokers become hyperactive after incubation with plasma prepared from blood of smokers obtained 10 min after smoking. This effect was not observed with presmoking plasma and could be inhibited in vitro by adding either catalase or reduced glutathione plus peroxidase to plasma or 2,6-di-tert-butyl-p-cresol (BHT) to platelets before incubation. Comparison of pre- and postsmoking plasma showed that smoking resulted in a decrease in vitamin E (18%, P < 0.01) and increases in conjugated diene (35%, P < 0.001), thiobarbituric acid-reactive substance (23%, P < 0.02), and free fatty acid (FFA, 40%, P < 0.005) plasma concentrations. The FFA fraction was peroxidized to a higher extent when extracted from postsmoking than from presmoking plasma. This peroxidized FFA fraction enhanced the thrombin-induced aggregation of platelets from nonsmokers. This increased response was inhibited either when the peroxidized FFA fractions were isolated from plasma treated with reduced glutathione and peroxidase or by pretreatment of the platelets with BHT. We conclude that the enhanced formation of lipid hydroperoxides found in postsmoking plasma seems to be responsible for the acute and marked platelet hyperactivity observed after smoking.

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