摘要:

AbstractEfforts to locate the active site for sulfur cyanolysis catalyzed by bovine serum albumin have led to systematic tests of several compounds that inhibit the catalyzed reaction. Hexanoate and 5‐dimethylaminonaphthalene‐1‐sulfonate bind at the same site and are partial inhibitors competitive with cyanide, uncompetitive with respect to sulfur. Various dansyl amino acids and 1‐anilino‐8‐naphthalene sulfonate display the same inhibitory behavior but bis (1‐anilino‐8‐naphthalene sulfonate) is a total inhibitor competitive with cyanide. These findings are interpreted to indicate that the cyanolysis active site is near, but not at, one of the short‐chain fatty acid binding sites on albumin subdomain 2‐AB or 3‐AB. Both ionic repulsion and steric considerations are implicated in the m

ISSN:0887-2082    

DOI:10.1002/jbt.2570050102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractThe ability of feprazone to induce the hepatic microsomal mixed‐function oxidases was investigated in the rat, with emphasis being placed on the nature of the cytochrome P‐450 family induced. Treatment with feprazone enhanced thep‐hydroxylation of aniline and the dealkylations of benzphetamine and pentoxyresorufin but had no effect on the O‐deethylation of ethoxyresorufin. The same treatment had no major effect on total cytochrome P‐450 levels but increased the spectral interaction of metyra‐pone with reduced cytochrome P‐450. Immunoblots employing monospecific polyclonal antibodies revealed that feprazone induces the apoprotein levels of the P450 II B, but not of the P450 I, family. It is concluded that feprazone is an inducer of the rat hepatic mixed‐function oxidase system showing selectivity toward the P

ISSN:0887-2082    

DOI:10.1002/jbt.2570050103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractBleomycin (BLM)‐induced lung fibrosis has been shown to be accompanied by the activation of poly(ADP‐ribose) polymerase and depletion of nicotinamide adenine dinucleotide (NAD) in the lung. Niacin, a precursor of NAD, was used in the present study to investigate its possible ameliorating effect on BLM‐induced pulmonary fibrosis in hamsters. Niacin (500 mg/kg IP) or saline (IP) was injected daily for 16 or 23 days. On day 3, hamsters were treated with BLM (7.5 U/5 mL/kg) or an equivalent volume of saline intratracheally. BLM alone significantly increased lung hydroxyproline levels, bron‐choalveolar lavage fluid protein concentration, and various inflammatory cell counts in the lavage in both experiments. In addition, BLM alone elevated prolyl hydroxylase and poly(adenosine‐5′‐diphosphate [ADP]‐ribose) polymerase activities in the 3‐week study. Niacin treatment significantly decreased BLM‐elevated lung hydroxyproline, prolyl hydroxylase, and poly(ADP‐ribose) polymerase activities. Histopa‐thology revealed that niacin treatment attenuated BLM‐induced thickened alveolar septa, foci of fibrotic consolidation, and accumulations of inflammatory cells in the parenchyma and air spaces. The ability of niacin to attenuate BLM‐induced lung fibrosis in hamsters suggests that it may have potential as an a

ISSN:0887-2082    

DOI:10.1002/jbt.2570050104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractThe mechanism by which chlordecone (CD) amplifies the hepatotoxicity of halomethanes such as CCl4, CHCl3, and BrCCl3has been a subject of intense study. Recent work has shown that suppression of hepatocellular regeneration leads to accelerated progression of liver injury leading to complete hepatic failure due to an unusual interaction between individually nontoxic low‐dose combination of CD and CCl4. Since polyamines are involved in cell division, their levels reflect the extent to which there is suppression of hepatocellular regeneration during CD and CCl4interaction. The present studies were designed to investigate the polyamine levels and associated enzymes in livers of rats treated with BrCCl3alone or CD and BrCCl3low‐dose combination in order to confirm whether the sequence of events of hepatotoxicity is similar to that seen in CCl4toxicity or that seen during CD and CCl4interaction. The extent of liver toxicity in rats fed 10 ppm chlordecone (CD) for 15 days prior to the injection of a single low dose of BrCCl3(15 μL/kg body weight) or after exposure to a high dose of BrCCl3(80 μL/kg body weight) without CD pretreatment, was similar 6 and 24 hr later as assessed by plasma transaminase levels. There was also an increase in transaminase levels, in rats exposed to a single low dose of BrCCl3alone (15 μL/kg body weight) but this increase was far below the high‐dose exposure alone or the combination treatment. Hepatic levels of ornithine decarboxylase, S‐adeno‐sylmethionine decarboxylase,N1‐acetylputrescine,N1‐acetylspermidine, putrescine, spermidine, and spermine at the end of 24 hr increased after exposure to a low dose of BrCCl3alone as compared to exposure to a high dose alone or the low‐dose combination of CD and BrCCl3. Liver spermidineN1‐acetyltrans‐ferase was elevated at 2, 6, and 24 hr after exposure to a high dose of BrCCl3alone as compared to treatment with a low‐dose combination of CD and BrCCl3suggesting decreased synthesis of this enzyme, in spite of a greater need as seen from liver transaminase levels. In general, it was observed that there is significant elevation in some polyamines and related enzymes during toxicity of a low dose of BrCCl3which seemed to stabilize within 24 hr. This was not observed with the other two groups of rats exposed either to BrCCl3high dose alone or the low‐dose combination of CD and BrCCl3. Results indicate that CD and BrCCl3low‐dose combination treatment causes increased liver toxicity resulting in compromised polyamine metabolism which is coincidental with suppressed hepatocellular regeneration leading to accelerated progressive phase of liver injury culminating in complete hepatic failure. These findings point to the possibility that the mechanism of potenti‐ation of BrCCl3hepatotoxicity by CD is similar to that s

ISSN:0887-2082    

DOI:10.1002/jbt.2570050105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractRepeated freezing and thawing, the addition of salts, and elevated temperatures all promote the inactivation of the rat hepatic Ah receptor. The reduced availability of bulk water to solvate the protein is proposed to be the factor linking all these routes for inactivation. Prospective protocols for purification of unliganded Ah receptor should therefore minimize the number of freeze/thaw cycles; long‐term freezing of cytosolic samples at −20°C is inadequate to maintain long‐term viability of the unliganded receptor. The stability of rat hepatic receptor is greatly increased upon binding the ligand, and the extent of ligand‐induced stabilization is much greater than what is observed with steroid hormone receptors. Concentrations of NaCl and K2HPO4up to 0.5 M inactivate the unbound Ah receptor irreversibly, with the loss of approximately 50% of the specific binding. At 2.0 M NaCl, a further reversible reduction in ligand binding activity is observed. The results at lower salt concentrations are interpreted in terms of the irreversible dissociation of a single binding unit from the trimeric cytosolic Ah receptor (which consists of two ligand‐binding units and a 90‐kDa heat shock protein), with the release of bound ligand from

ISSN:0887-2082    

DOI:10.1002/jbt.2570050106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractAflatoxin B1‐DNA adduct concentrations were measured in the livers of adult Sprague‐Dawley CD rats treated on days 2, 4, and 6 postnatally with 1.45 μmol of diethylstilbestrol and in adulthood with phenobarbital, 3‐methylchlanthrene, or vehicle prior to treatment with aflatoxin B1. Aflatoxin B1(1 mg/kg) was injected 5 hr prior to killing the rats. Female rats exposed neonatally to diethylstilbestrol had significantly higher aflatoxin B1‐DNA adduct concentrations (three‐ to sixfold) than adult female rats treated neonatally with propylene glycol. Liver aflatoxin B1‐DNA adduct concentrations were slightly higher in control males as compared to adduct concentrations in neonatally diethylstilbestrol‐treated males, as compared to adduct concentrations in control females (not significant [NS]). Phenobarbital and 3‐methylcholanthrene treatment followed by aflatoxin B1injection resulted in decreased aflatoxin B1‐DNA adduct concentrations in all rats. Our results demonstrate that neonatal exposure to diethylstilbestrol alters the capacity of adult female rats to form and/or dispose of carcinogen‐DNA adducts following a single dose of aflatoxin B1(increased adduct concentration). This alteration may be a consequence of altered imprinting mechanisms with diethylstilbestrol causing developmental modifications early in life. The animals were, however, able to respond to cytochrome P‐450 and P‐448 inducers as evidenced by decreased aflatoxin B1

ISSN:0887-2082    

DOI:10.1002/jbt.2570050107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractEight methylenedioxyphenyl (MDP) compounds were examined for their ability to induce cytochrome P450 (P450) in mouse liver. Induction by safrole, isosafrole, and dihydrosafrole was studied in both C57BL/6N (Ah‐responsive) and DBA/2N (Ahnonresponsive) male mice after IP administration of 200 mg/kg/day MDP compound for 3 days. Hepatic P450 content, ethylmorphineN‐demethylase, ethoxy‐resorufin O‐deethylase, and acetanilide hydroxylase activities were induced to the same extent in both strains of mice. Benzo(a)pyrene hydroxylase activity, however, was not induced in either C57 or DBA mice. The similarity of results in both strains of mice indicated induction of these P450 isozymes by these three MDP compounds is not mediated by the Ah receptor. Induction of P450 by butylbenzodioxole (n‐butyl‐BD), tertiarybutylbenzodioxole (t‐butyl‐BD), methylbenzodioxole (methyl‐BD), nitrobenzodioxole (nitro‐BD), and bromobenzodioxole (bromo‐BD) was examined only in C57BL/6N mice. Methyl‐BD, nitro‐BD, and bromo‐BD did not induce hepatic microsomal proteins or selected P450 monooxygenase activities. In contrast,n‐butyl‐BD, andt‐butyl‐BD induced P450 content, ethylmorphineN‐demethylase, acetanilide hydroxylase, and ethoxyresorufinO‐deethylase activities. Benzo(a)pyrene hydroxylase was not induced by any of the treatments. Induction of these P450 activities is consistent with induction of P450 IIB1 and P450 IA2, but not induction of P450 IA1. Western blot analysis with antibodies to P450 isozymes induced with either phenobarbital (Pb) or 3‐methylcholanthrene (3‐MC) confirmed that both IIB1 and IA2

ISSN:0887-2082    

DOI:10.1002/jbt.2570050108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractThe effects of pretreatment with symmetrically dihalogenated biphenyls (DXBs, X‐F, Cl(C), Br(B) and I) on rat liver drug metabolism enzymes were investigated. 4,4′‐DFB, ‐DCB, and ‐DBB as well as 2,2′‐DFB appeared to be inducers of microsomal cytochrome P‐450‐linked monoxygenases (N‐demethylases of aminopyrine and ethylmorphine). However, no structure‐induction relationship was found. 4,4′‐DXBs also induced a cytochrome P‐448‐linked mono‐oxygenase (ethoxyre‐sorufinO‐deethylase), and their order of induction potential seemed to parallel the increase of the size of the halogen substituent. Therefore, 4,4′‐DXB's may be categorized as mixed‐type inducers, the cytochrome P‐450 component being the more pronounced. Data on the cytochrome P‐448 induction by dihalogenated biphenyls with only para substituents may be considered as a refinement of the previously described structure‐activity relationship in this respect. All of the DXBs except 3,3′‐DCB and 4,4′‐DIB, enhanced, like phenobarbital, the activity of UDP‐glucuronyltransferase toward 4‐hydroxybiphenyl. Only 4,4′‐DFB was able to induce the activity of glutathione S‐transferase toward 1,2‐epoxy‐3‐(p‐nitrophenoxy)propane. Studies after 4,4′‐DBB‐treatment revealed, like phenobarbital, a preferential induction of ethylmorphineN‐demethylase on rough endoplasmic reticulum‐derived microsomes, whereas UDP‐glucuronyltransferase activity toward 4‐hydroxybiphenyl was induced to a larger extent on smooth endoplasmic re

ISSN:0887-2082    

DOI:10.1002/jbt.2570050109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

ISSN:0887-2082    

DOI:10.1002/jbt.2570050110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractPhospholipase A1, A2, and C and diacylglycerol lipase activities were measured in cell sonicates after exposing confluent monolayers of porcine pulmonary artery endothelial cells to 5 ppm NO2, a toxic constituent of environmental pollution, for 24 and 48 hr. There was a significant increase (2.25‐fold) in phospholipase A1activity in 24 and 48 hr NO2‐exposed cells, whereas activities of phospholipases A2and C and diacylglycerol lipase were comparable to control cells at both time points. When endothelial cells were prelabeled with [3H]‐arachidonic acid and then exposed to NO2for 48 hr, increased counts were recovered from cell lysophospholipids with concomitant decreased recovery of counts from cell phosphatidylcholine and phosphatidylethanolamine. These results demonstrate that NO2exposure results in specific activation of phospholipa

ISSN:0887-2082    

DOI:10.1002/jbt.2570050111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY