Abstract:
:A number of synthetic manganese complexes exhibit both in vitro and in vivo catalytic antioxidant activities. This study reports that the antioxidant potencies of a new series of meso-N,N'-dialkyl-imidazolium substituted manganese(III) porphyrins are dependent, in part, on their ability to redox cycle with endogenous flavin-dependent oxidoreductases. Inhibition of lipid peroxidation activities of these novel cationic porphyrins was compared using rat brain homogenate as a source of lipids and endogenous oxidoreductases. Iron and ascorbate was used as initiators of lipid peroxidation, and two indices of lipid peroxidation (thiobarbituric acid reactive species (TBARS) and F(2)-isoprostanes) were determined. All meso-N,N'-dialkyl-imidazolium substituted porphyrins tested were potent inhibitors of lipid peroxidation with IC(50) ranging from 0.1 to 34 microM with a metal-dependent potency of Mn(III)>Co(III)>Zn(II). A flavin-dependent oxidoreductase antioxidant process was supported by the ability of the diphenyleneiodonium chloride (DPI, a flavoenzyme inhibitor) to decrease the potency of Mn-porphyrins in the lipid peroxidation model and that Mn-porphyrins stimulate NADPH oxidation in rat brain homogenates. These data suggest that metalloporphyrins may have differential antioxidant effects in tissues due to the presence or absence of flavin-dependent oxidoreductases.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Kachadourian R,Johnson CA,Min E,Spasojevic I,Day BJdoi
10.1016/j.bcp.2003.08.036subject
Has Abstractpub_date
2004-01-01 00:00:00pages
77-85issue
1eissn
0006-2952issn
1873-2968pii
S000629520300683Xjournal_volume
67pub_type
杂志文章abstract::Prostaglandin synthetase has the ability to catalyze the metabolism of paracetamol to a reactive metabolite, which binds to protein and reduced glutathione (GSH). This was demonstrated with microsomes isolated from both sheep seminal vesicles (SSV) and rabbit kidney medulla. The activation of paracetamol occurred thro...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90029-6
更新日期:1982-04-01 00:00:00
abstract::Cobalt protoporphyrin generated from 5-amino[4-14C]laevulinate by homogenates or primary cultures of chick embryo liver exposed to CoCl2 was found to be radioactivity unextractable by acid/acetone, when extra protein was added. The activity of ferrochelatase was required for formation of cobalt protoporphyrin since in...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90333-1
更新日期:1982-03-15 00:00:00
abstract::1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is believed to induce neurotoxicity by inhibiting mitochondrial oxidative metabolism, whereas acetyl-L-carnitine (ALC) facilitates this process by transporting fatty acids into mitochondria for beta oxidation. We investigated whether large doses of ALC given by gavag...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90034-t
更新日期:1993-05-25 00:00:00
abstract::The cellular distribution of AcCoA:arylamine N-acetyltransferase (NAT; EC 2.3.1.5) activities was examined in the rat small intestine to determine if heterogeneous cellular distribution contributes to preferential tumor development in the colonic region after exposure to heterocyclic amines (HAs). A chelation/elution ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00659-x
更新日期:1998-05-01 00:00:00
abstract::We describe the synthesis and the pharmacological characterization of a new quaternary selective serotonin reuptake inhibitor (SSRI) N-methyl-citalopram (NMC) with periphery restricted action due to its inability to cross the blood brain barrier. NMC recognized and blocked the human platelet serotonin transporter (SER...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.07.035
更新日期:2010-11-15 00:00:00
abstract::The use of NMR methods to study conformational and dynamic aspects of the proline residues in the nonapeptide bradykinin is reviewed. NMR analyses involve considerations of bistable equilibria which include the cis/trans conformational heterogeneity of the imide bond, the cis'/trans' regions of conformational stabilit...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90176-l
更新日期:1990-07-01 00:00:00
abstract::Quinones are ubiquitously present in mammals and their environment. They are involved in physiologic functions such as electron transport but are also toxic compounds. In particular, quinone-quinol redox cycles may lead to oxidative stress, and arylating quinones have been demonstrated to activate endoplasmic reticulu...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2011.12.006
更新日期:2012-04-01 00:00:00
abstract::Glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGTs), is a crucial substance metabolism and elimination process that mostly occurs in the liver to protect the body from toxic substances and maintain homeostasis. The reaction functions well in a uridine diphosphate glucuronic acid (UDPGA) -dependent manner...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2019.113753
更新日期:2020-02-01 00:00:00
abstract::Diazepam (DZ), N-desmethyl diazepam (NOR) and temazepam (TEM) were used as substrates in drug metabolism studies to characterize the changes in cytochrome P-450 mono-oxygenase pathways in hepatocytes isolated from cynomolgus monkeys, during culture for 6 days. Hepatocytes were incubated with DZ (20 microM), NOR (6 mic...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90547-9
更新日期:1989-08-15 00:00:00
abstract::Nephrotoxicity due to renal proximal tubule accumulation of aminoglycoside (AG) antibiotics, such as gentamicin, represents a major clinical problem. Receptor-mediated endocytosis via the multi-ligand receptor megalin is thought to be a key mechanism in the cellular uptake of AGs and nephrotoxicity. This process can b...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.09.021
更新日期:2010-02-15 00:00:00
abstract::Alpha2-adrenoceptor agents as well as stress affect the activity of several hepatic monoxygenases including those related to CYP1A enzymes. This study was therefore designed to assess the role of central and/or peripheral catecholamines and, in particular, of adrenoceptors in the regulation of B(alpha)P-induced cytoch...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.09.024
更新日期:2005-01-15 00:00:00
abstract::Adenosine triphosphate (ATP) is a molecule that on one hand plays a central role in cellular energetics and which on the other is a ubiquitous signaling molecule when released into the extracellular media. Extracellular ATP accumulates in inflammatory environments where it acts as a damage-associated molecular pattern...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2020.114385
更新日期:2020-12-20 00:00:00
abstract::We investigated the effects of tranilast on inducible cyclooxygenase (COX2)-mediated prostaglandin E2 (PGE2) production and enzyme induction in interleukin-lbeta (IL-1beta)-stimulated cultured dermal fibroblasts. IL-1beta enhanced PGE2 production in cultured fibroblasts. Tranilast did not affect constitutive cyclooxyg...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00187-1
更新日期:1997-06-15 00:00:00
abstract::The constitutive androstane receptor (CAR; NR1I3) is a nuclear receptor responsible for the recognition of potentially toxic endo- and exogenous compounds whose elimination from the body is accelerated by the CAR-mediated inducible expression of metabolizing enzymes and transporters. Despite the importance of CAR, few...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.08.014
更新日期:2008-11-15 00:00:00
abstract::L-Carnitine is a key molecule in the transfer of fatty acid across mitochondrial membranes. Bioavailable L-carnitine is either provided by an endogeneous biosynthesis or after intestinal absorption of dietary items containing L-carnitine. After intestinal absorption or hepatic biosynthesis, L-carnitine is transferred ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00110-2
更新日期:2003-05-01 00:00:00
abstract::The increasing incidence of severe liver diseases worldwide has resulted in a high demand for curative liver transplantation. Unfortunately, the need for transplants by far eclipses the availability of suitable grafts leaving many waitlisted patients to face liver failure and often death. Routine use of smaller grafts...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2020.113847
更新日期:2020-05-01 00:00:00
abstract::Pig articular cartilage, overlaid with a minced preparation of synovium from the same joint, underwent extensive matrix degradation during a two-week culture period. This degradation was associated with de novo synthesis by the synovium of specific neutral proteoglycan- and collagen-degrading enzymes. Both enzymes exh...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90179-5
更新日期:1984-04-15 00:00:00
abstract::The effects of 3-monoalkyl- and 3,5-dialkyl-substitution on the cytotoxicity of paracetamol (PAR) in rat hepatocytes was studied. PAR is known to be bioactivated by the hepatic microsomal cytochrome P-450 containing a mixed-function oxidase system presumably to N-acetyl-para-benzoquinone imine (NAPQI), a reactive meta...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90653-2
更新日期:1986-11-01 00:00:00
abstract::Piperine and two of its derivatives, antiepilepsirine (AE or 3,4-methylendioxycynnamoylpiperine) and compound 7448 (N-isopropyl 3 (4 chloro-phenyl) propenoylamide) are very effective in stimulating serotonin (5HT) synthesis. AE raises the ratio of free-to-bound tryptophan (TP) in plasma and induces a long-lasting incr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90055-8
更新日期:1984-12-01 00:00:00
abstract::Thioredoxin reductase (TR1) is a selenoprotein that is involved in cellular redox status control and deoxyribonucleotide biosynthesis. Many cancers, including lung, overexpress TR1, making it a potential cancer therapy target. Previous work has shown that TR1 knockdown enhances the sensitivity of cancer cells to antic...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.09.024
更新日期:2011-01-15 00:00:00
abstract::To identify needed human equilibrative nucleoside transporter 4 (hENT4) inhibitors, we cloned and stably expressed the recombinant protein in PK15NTD (nucleoside transporter deficient) cells, and, investigated its interaction with a series of dipyridamole analogs synthesized in our laboratory. Compounds were tested in...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.08.063
更新日期:2013-12-01 00:00:00
abstract::Phenylbutyrate has been shown recently to induce fetal hemoglobin (HbF) production in patients with sickle cell anemia and beta thalassemia. We have now examined related aromatic fatty acids in order to define the range of active structures and identify plausible mechanisms of action. Structure-function analysis revea...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(96)00476-5
更新日期:1996-10-25 00:00:00
abstract::Previous reports have indicated that insulin administration triggers an early increase in plasma tryptophan (TRP) levels in fasted rats. Then, the present study was undertaken to investigate the putative role of liver tryptophan pyrrolase (TPO) in this short-term effect of insulin. In 24 hr fasted rats, doses of insul...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90312-9
更新日期:1990-08-15 00:00:00
abstract::Adult hepatocytes from rat and man were maintained for 2 weeks between two gel layers in a sandwich configuration to study the influence of this culture technique on the preservation of basal activities of xenobiotic-metabolizing phase I and phase II enzymes. The response of these enzyme activities to an enzyme induce...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00204-9
更新日期:1997-10-01 00:00:00
abstract::The present study was designed to evaluate the radioprotective effect of N- acetylcysteine (NAC) on gamma-radiation induced toxicity in hepatic tissue in rat. The cellular changes were estimated using malondialdehyde (MDA, an index of lipid peroxidation), superoxide dismutase (SOD), glutathione peroxidase (GSHPx), red...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.09.018
更新日期:2008-02-01 00:00:00
abstract::In this study, we showed that oligogalacturonic acid (OGA) purified from flax pectin inhibit in vitro osteoclastic bone resorption in a dose-dependent manner. The OGA inhibitory effect was neither linked to an effect on osteoclast apoptosis, nor to an inhibition of cathepsin K activity. By means of an in vitro collage...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.07.014
更新日期:2009-12-15 00:00:00
abstract::Isolated rat liver mitochondria have been incubated in the presence of the general anesthetic 2,6-diisopropylphenol (0-100 microM) and the efficiency of oxidative phosphorylation has been evaluated by measuring the respiratory rates, the rates of ATP synthesis or hydrolysis and the magnitude of the transmembrane elect...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90684-w
更新日期:1991-06-21 00:00:00
abstract::Sustained activation of AMP-activated protein kinase (AMPK) induces apoptosis in several cell types. In pancreatic beta cells this occurs under glucose limitation, or in the presence of the pharmacological AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR). It is unknown whether Akt activation can countera...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.02.019
更新日期:2008-05-15 00:00:00
abstract::Despite tobacco being highly addictive, it is unclear if nicotine has significant affective properties. To address this, we studied taste reactions to gustatory stimuli, palatable sucrose and unpalatable quinine, which are believed to reflect ongoing affective state. Taste reactivity was assessed during chronic nicoti...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.06.017
更新日期:2009-10-01 00:00:00
abstract::The ability of adrenergic catechol derivatives, including dobutamine, dopamine, and isoproterenol, to inhibit lipid peroxidation was examined. All the catechol derivatives we tested strongly inhibited lipid peroxidation. Dobutamine was a more powerful inhibitor of iron-catalyzed lipid peroxidation than the other agent...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(98)00075-6
更新日期:1998-06-15 00:00:00