Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Aflatoxin B1”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources
PubMed1992

Mutagenic activation of aflatoxin B1 by pulmonary, renal, and hepatic cytochrome P450s from rats.

The genotoxic and mutagenic activation of aflatoxin B1 (AFB1) by hepatic, renal, and pulmonary microsomes and purified cytochrome P450s was investigated in Salmonella typhimurium TA1535/pSK1002 cells in which an umu response shows DNA damage. The activity of the hepatic microsomes was greatest. Pulmonary microsomes had moderate activity and renal microsomes had low activity. P450 2C11, 2B1, 3A2, 4A2, 4B1, K-2, and K-4 were assayed in a reconstituted system with dilauroylphosphatidylcholine (DLPC). P450 2C11 (a major hepatic cytochrome P450 in male rats) had high activity. P450 2B1 (a major form as well as P450 4B1 in pulmonary microsomes) and K-2 (a minor form in renal microsomes) had moderate activity. P450 4A2 (a major form in renal microsomes), P450 K-4 (a renal form), and P450 4B1 had low activity. P450 3A2 did not have high activity in these conditions but it had high activity toward AFB1 in a modified reconstituted system with a lipid mixture and sodium cholate instead of DLPC only. The activities of other forms were not enhanced by the modification of reconstituted system. Anti-P450 2C11 or 3A2 antibodies inhibited the bioactivation of AFB1 by hepatic microsomes to 50%. These results suggest that the greater ability of hepatic microsomes as compared with pulmonary and renal microsomes to metabolize AFB1 to mutagenic products is a function of the relative proportions of the highly active cytochrome P450s, P450 2C11 and 3A2, in the liver.

Aflatoxin B1↗
PubMed1999

Enhanced duck hepatitis B virus gene expression following aflatoxin B1 exposure.

Epidemiological studies have suggested synergistic interactions between chronic hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure in the etiology of hepatocellular carcinoma (HCC), although the molecular mechanisms of their interactions are still not understood. The aim of this study was to use the Pekin duck model to investigate the impact of AFB1 exposure on duck hepatitis B virus (DHBV) replication during the early stages of virus-carcinogen interactions. Six-week-old chronic DHBV-carrier or uninfected ducks were exposed to AFB1 for 5 weeks or treated with dimethylsulfoxide (DMSO) as a control. Animals were observed for 6 to 13 weeks after AFB1 treatment to study the influence of AFB1 exposure on DHBV replication and liver pathologies. Histological analysis showed more marked changes in the livers of AFB1-treated ducks, and these were enhanced by DHBV infection. A significant increase in serum and liver DHBV DNA level was observed in AFB1-treated ducks as compared with DMSO-treated controls. In addition, viral RNAs, in particular the pregenomic RNA that is the template of viral replication, and intrahepatic DHBV DNA replicative intermediates, were significantly increased by AFB1 treatment. Moreover, an overexpression and accumulation of DHBV large envelope (L) protein was observed in the hepatocytes of AFB1-exposed animals. The in vitro study has further confirmed an increase in intracellular viral DNA and in virus release in AFB1-treated primary duck hepatocytes. Taken together, our results indicate that AFB1 exposure leads to an increase in virus gene expression associated with intrahepatic accumulation of DHBV L protein and enhanced liver pathology.

Aflatoxin B1↗
PubMed1997

Conjugation of highly reactive aflatoxin B1 exo-8,9-epoxide catalyzed by rat and human glutathione transferases: estimation of kinetic parameters.

Aflatoxin B1 (AFB1) exo-8,9-epoxide, the reactive product of the hepatocarcinogen AFB1, is stable in aprotic solvents but hydrolyzes rapidly in H2O at 25 degrees C and pH 7 (t1/2 = 1 s). However, it is also known that some glutathione (GSH) transferases can conjugate the epoxide with GSH to give the adduct in high yield. We developed an approach to estimating kinetic parameters for reactions involving this epoxide or other substrates that are unstable to H2O. Varying concentrations of the (anhydrous) epoxide and GSH transferase were mixed and the GSH conjugates were measured. The final concentrations of product were known for each set of the starting epoxide and enzyme concentrations in a modeling approach, where the competition with the hydrolysis reaction is considered with two variables, a K for binding of the enzyme and epoxide and a rate k2, which includes microscopic steps following complex formation and resulting in conjugate formation. The ratio k2/K, a measure of enzyme efficiency, varied among individual recombinant GSH transferases in the the order (rat) 10-10 >> 3-3 > (human) M1-1 > T1-1 > A1-1 > P1-1 > A2-2, from 3 x 10(6) to 10 M(-1) s(-1). The high ratio of M1-1 among the human GSH transferase enzymes tested is consistent with other work in which GSH-AFB1 conjugates were not detected in hepatocytes with an M1 null polymorphism. This general kinetic approach should be applicable to estimation of kinetic parameters involved in the interaction of other unstable substrates with enzymes.

Aflatoxin B1↗
PubMed2005

Teratogenic effects in rabbits of simultaneous exposure to ochratoxin A and aflatoxin B1 with special reference to microscopic effects.

To elucidate the teratogenic effects, ochratoxin A (OTA) and aflatoxin B1 (AFB1) were dissolved in corn oil and administered in combination to New Zealand White rabbits during 6-18 days of gestation orally with the dose levels of OTA+AFB1, 0.05+0.05 and 0.1+0.1mg/kg body weight. To assess pathomorphological features of the anomalies, the fetal serial sections were histologically examined. There was no mortality in any of the treated groups. Body weights and body weight gains of dams in the combined treatment groups were comparable with those of controls and individual treatments. The mean crown to rump lengths in both the combination dose groups and mean fetal weights in high dose combination group were significantly decreased. In the high dose combination, there was increase in the percent of implants resorbed and significant increase in the incidence of visceral anomalies. The combination treatment resulted in various gross, skeletal and visceral anomalies such as wrist drop, scoliosis, bent metacarpals, rudimentary ribs, cardiac defects and microphthalmia. There was a dose-related increase in the percent of litters showing the histopathological changes in the fetal tissues. The incidence of histopathological changes in the tissue sections prepared from fetal liver, kidneys, brain, heart and eyes was found increased in the high dose combination group. The comparative evaluation of the results of combination versus individual treatments revealed that certain anomalies observed in the individual treatment of OTA such as knuckling of fetlock, rudimentary tail or agenesis of tail, wavy ribs, hydrocephalus and agenesis of kidney and AFB1 as enlarged eye sockets and enlarged liver were absent in the combination treatment. However, some new manifestations such as cardiac defects and scoliosis were seen. The results of the present study indicated that in combination, OTA and AFB1 have antagonistic interaction. The presence of subtle lesions histologically due to an interference with normal development suggested that microscopic examination of the fetal tissues could provide additional, useful information to a developmental toxicity study.

Aflatoxin B1↗
PubMed1981

Enhanced susceptibility to aflatoxin B1 toxicity in weanling mice pretreated with carbon tetrachloride.

Weanling male mice with or without prior treatment with CCl4 (0.5 ml/kg) were exposed to either single (20.5, 25.6, 32 and 40 mg/kg) or multiple (4 mg/kg for 10 days or 8 mg/kg for 5 days) doses of aflatoxin B1. Evidence of its acute toxic and carcinogenic effects was found only in CCl4 pre-treated mice. Single dose LD 50 value under these conditions was calculated to be 26.8 mg/kg. Histological changes which predominantly occurred in the liver were characterized by acute necrosis and degeneration of the parenchymal cells. Hepatomas were observed as early as 9 months of age in CCl4 pre-treated animals given 4 mg/kg aflatoxin daily for 10 days. It is thus suggested that the repeated use of CCl4 as an anthelmintic in animals which are apparently resistant to the lethal and hepatocarcinogenic action of aflatoxin might increase their sensitivity to this mycotoxin.

Aflatoxin B1↗
PubMed2000

In vitro metabolism of aflatoxin B1 by larvae of navel orangeworm, Amyelois transitella (Walker) (Insecta, Lepidoptera, Pyralidae) and codling moth, Cydia pomonella (L.) (Insecta, Lepidoptera, Tortricidae).

Larvae of the navel orangeworm (NOW), Amyelois transitella (Walker), a major pest of almonds and pistachios, and the codling moth (CM), Cydia pomonella (L.), the principal pest of walnuts and pome fruits, are commonly found in tree nut kernels that can be contaminated with aflatoxin, a potent carcinogen. The ability of larvae of these insects to metabolize aflatoxin B1 (AFB1) was examined. A field strain of NOW produced three AFB1 biotransformation products, chiefly aflatoxicol (AFL), and minor amounts of aflatoxin B2a (AFB2a) and aflatoxin M1 (AFM1). With AFL as a substrate, NOW larvae produced AFB1 and aflatoxicol M1 (AFLM1). A lab strain of CM larvae produced no detectable levels of AFB1 biotransformation products in comparison to a field strain which produced trace amounts of only AFL. Neither NOW nor CM produced AFB1-8,9-epoxide (AFBO), the principal carcinogenic metabolite of AFB1. In comparison, metabolism of AFB1 by chicken liver yielded mainly AFL, whereas mouse liver produced mostly AFM1 at a rate eightfold greater than AFL. Mouse liver also produced AFBO. The relatively high production of AFL by NOW compared to CM may reflect an adaptation to detoxify AFB1. NOW larvae frequently inhabit environments highly contaminated with fungi and, hence, aflatoxin. Only low amounts, if any, of this mycotoxin occur in the chief CM hosts, walnuts, and pome fruits. Characterizations of enzymes and co-factors involved in biotransformation of AFB1 are discussed.

Aflatoxin B1↗
PubMed2000

Preliminary evidence that degradation of aflatoxin B1 by Flavobacterium aurantiacum is enzymatic.

The ability of crude protein extracts from Flavobacterium aurantiacum to degrade aflatoxin B1 (AB1) in aqueous solution was evaluated. Crude protein extracts (800 microg of total protein per ml) degraded 74.5% of AB1 in solution. An average of 94.5% of AB1 was recovered after incubation with heat-treated crude protein extracts (800 microg of total protein per ml). DNase I-treated crude protein extracts degraded 80.5% of AB1 in solution, suggesting that removal of aflatoxin by F. aurantiacum is not due to nonspecific binding with the bacterium's genomic DNA. Proteinase K-treated crude protein extracts degraded 34.5% of AB1, providing evidence that degradation of aflatoxin is linked to a protein that is possibly an enzyme. Solution pH affected the amount of AB1 degraded by crude protein extracts after 24 h. Maximum degradation was observed at pH 7 (pH levels tested: 5, 6, 7, and 8), with some AB1 degradation occurring at pH levels as low as 5 and as high as 8. Acidic pH levels were more detrimental to the ability of crude protein extracts to degrade AB1 than was basic pH. The results of this work indicate that the degradation of AB1 by F. aurantiacum may be enzymatic.

Aflatoxin B1↗
PubMed1990

Altered benzo[a]pyrene metabolism in C3H/10T1/2 cells transformed by aflatoxin B1 or 3-methylcholanthrene.

C3H/10T1/2 clone 8 (10T1/2) cells possess Phase I and Phase II xenobiotic metabolizing enzymes associated with the metabolism of polycyclic aromatic hydrocarbons to activated or detoxified species. We compared the metabolism of benzo[a]pyrene (BaP) by these cells to an aflatoxin B1 (AFB1)-transformed line (7SA) and a 3-methylcholanthrene (3-MC)-transformed line (MCA) isolated from carcinogen-treated 10T1/2 cells. Relative to 10T1/2 cells, basal levels of cytochrome P450-mediated aryl hydrocarbon hydroxylase (AHH) were significantly depressed in 7SA cells by about 30%. The inducibility of AHH by BaP treatment was depressed by 30-70% in MCA and 7SA cells over a 36-hr time course. 10T1/2 and MCA cells accumulated similar intracellular amounts of 3-OH-BaP by 12 and 24 hr, respectively; in contrast the accumulation of 3-OH-BaP in 7SA cells was 70% lower. During 36 hr of BaP treatment, total BaP-DNA adduct levels formed in 7SA and MCA cells, determined by 32P-postlabeling analysis, were 90 and 83% lower, respectively, than those found in 10T1/2 cells. These differences in response to BaP treatment were not related to cellular differences in the uptake or efflux of BaP. Relative to 10T1/2 or MCA cells, 7SA cells were found to have at least a twofold increase in UDP-glucuronyltransferase activity, which correlated with the lower intracellular accumulation of 3-OH-BaP and enhanced formation of extracellular polar metabolites. MCA cells had an almost twofold increase in glutathione S-transferase activity relative to parental 10T1/2 cells but produced lower levels of extracellular polar metabolites. These results demonstrate an association between chemical transformation of 10T1/2 cells and altered xenobiotic metabolism. This system may provide an in vitro model for examining the molecular events responsible for the biochemically altered phenotype of the malignantly transformed cell.

Aflatoxin B1↗
PubMed1988

Modification of aflatoxin B1 biotransformation in vitro and DNA binding in vivo by dietary broccoli in rats.

Cruciferous vegetables have been shown to have anticarcinogenic effects in animals but biochemical mechanisms have not been completely elucidated. The effects of dietary broccoli on in vivo DNA binding of the hepatocarcinogen aflatoxin B1 (AFB) and in vitro formation of the putative carcinogenic intermediate, AFB-8,9-epoxide, as well as detoxification of the epoxide by conjugation with glutathione (GSH), were examined in this study. Animals were fed a purified diet, a purified diet plus 25% freeze-dried broccoli, or standard rodent chow for 3 wk. In vivo binding of AFB to hepatic DNA was determined. Biotransformation of AFB in vitro (microsomal oxidation to AFB-8,9-epoxide, as well as hydroxylated metabolites, and cytosolic GSH conjugation of AFB-8,9-epoxide generated in situ) was measured by an HPLC method that allows specific and direct determination of AFB metabolites and thus, the rates of their formation. Microsomal mixed-function oxidase and epoxide hydrolase activities and cytosolic glutathione S-transferase activities were also measured with commonly used surrogate substrates. The rate of cytosolic conjugation of AFB-8,9-epoxide was increased 2.8-fold by the broccoli diet and 2.2-fold by the chow diet. These changes were not fully reflected by increases in activity with surrogate substrates. The chow diet did not affect epoxide hydrolase activity nor glutathione S-transferase activity toward 3,4-dichloronitrobenzene or benzo[a]pyrene 4,5-oxide, whereas these activities were significantly increased by the broccoli diet. Microsomal formation of AFB-8,9-epoxide was unaffected by the dietary treatments, whereas formation of aflatoxin M1 was increased. The chow diet, but not the broccoli diet, increased the amount of aflatoxin Q1 formed from AFB. Binding of AFB to DNA in vivo was significantly lower in the broccoli group but not in the chow-fed animals. These results indicate that broccoli contains substances that cause a reduction in the binding of AFB metabolites to DNA, possibly through the induction of glutathione S-transferase(s). Broccoli and rodent chow differ in their constituents that increase levels of xenobiotic biotransformation enzymes relative to a purified diet. The results also indicate the limitations of reliance on measurements of biotransformation pathways using surrogate substrates instead of carcinogenic compounds of interest.

Aflatoxin B1↗
PubMed1982

Initiation of C3H/10T1/2 cell transformation by N-methyl-N'-nitro-N-nitrosoguanidine and aflatoxin B1.

The utility of C3/H/10T1/2 mouse embryo fibroblasts for the detection of carcinogenic substances has been limited by their apparent insensitivity to the oncogenic effects of direct-acting alkylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and procarcinogens such as aflatoxin B1 (AFB1). Because the process of C3H/10T1/2 transformation can be observed to proceed through discrete stages of initiation and promotion, we have considered the possibility that MNNG and AfB1 may only initiate C3H/10T1/2 transformation. Treatment of asynchronous C3H/10T1/2 cells with MNNG or AfB1 alone generally produced few transformed foci. If MNNG or AfB1 treatment was followed by the exposure of cells to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), numerous transformed foci were produced. Phorbol did not enhance transformation by either substance. MNNG and AfB1 thus appear to be initiating agents for transformation. TPA also enhanced the transformation of C3H/10T1/2 cells by low doses of 3-methylcholanthrene (3-MCA), but transformation by high concentrations of 3-MCA was inhibited by the presence of TPA. These studied suggest that the sensitivity of the C3H/10T1/2 transformation system to potential carcinogens can be dramatically heightened if the bioassay is conducted in the presence and absence of TPA.

Aflatoxin B1↗
PubMed1989

In vivo effect of dietary factors on the molecular action of aflatoxin B1: role of riboflavin on the catalytic activity of liver fractions.

Weanling rats were kept on a synthetic riboflavin-free diet for 4 weeks, and subsequently on the same diet but supplemented with riboflavin for 2 weeks. The ability of liver microsomes to catalyze reactions of aflatoxin B1 (AFB1) leading to its activation and DNA adduct formation was measured after each period of experimental feeding. A decrease in both activities was evident during riboflavin deficiency, and this could be restored after normal supply of the vitamin. The decrease was attributed to a fall in the endogenous flavin content, specifically the coenzyme flavin adenine dinucleotide which forms an integral part of the microsomal monooxygenase that catalyzes the activation reactions. The vitamin and its coenzymes, however, inhibit the microsomal enzyme activity when added in excess in the in vitro system. It is envisaged that riboflavin may play a role in regulating the carcinogenic activity of AFB.

Aflatoxin B1↗
PubMed1997

CYP1A induction by beta-naphthoflavone, Aroclor 1254, and 2,3,7,8-tetrachlorodibenzo-p-dioxin and its influence on aflatoxin B1 metabolism and DNA adduction in zebrafish.

This study investigated the inductive response of cytochrome P4501A (CYP1A) in the zebrafish (Danio rerio) following exposure to Aroclor 1254, beta-naphthoflavone (betaNF), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and then investigated TCDD modulation of aflatoxin B1 (AFB1) metabolism and hepatic AFB1-DNA adduction. Aroclor 1254 fed at 500 ppm for 1 to 9 days or intraperitoneal (ip) injection of 75-200 mg Aroclor 1254/kg body weight failed to induce CYP1A protein or associated 7-ethoxyresorufin-O-deethylase (EROD) activity. By contrast, dietary betaNF at 500 ppm for 3 or 7 days induced CYP1A protein and EROD activity approximately threefold above controls. A single ip injection of 150 mg/kg betaNF showed maximal induction of CYP1A protein and EROD activity near 24 hr, both of which decreased to control levels during the next 6 days. Single ip administration of 25, 50, 100, or 150 mg betaNF/kg body weight provided dose-responsive increases in CYP1A and EROD activity. Dietary exposure to 0.75 ppm TCDD for 3 days also significantly induced CYP1A and EROD. The effect of TCDD on the metabolism of [3H]AFB1 in zebrafish was then investigated. The major [3H]AFB1 metabolites excreted in water over 24 hr in the control group were aflatoxicol, aflatoxicol-glucuronide, and parent AFB1. By contrast, the predominant metabolites in the TCDD-pretreated group were aflatoxicol-M1-glucuronide, aflatoxicol, aflatoxin M1 plus aflatoxicol-M1 (unresolved), aflatoxicol-glucuronide, and parent AFB1. Surprisingly, hepatic AFB1-DNA adduction was approximately fourfold higher in the TCDD treated group than in controls. This significant difference could not be explained by increased capacity for bioactivation of AFB1 as measured by an in vitro AFB1-exo-8, 9-epoxide trapping assay. However, it was demonstrated that both control and induced zebrafish have high capacity to bioactivate aflatoxin M1 to a reactive intermediate, such that secondary bioactivation of this genotoxic intermediate may be responsible for the increased DNA binding.

Aflatoxin B1↗
PubMed1989

Mutagenic activation of aflatoxin B1 by P-450 HFLa in human fetal livers.

The genotoxic and mutagenic activation of promutagens by human fetal livers was measured by the induction of umu gene expression in Salmonella typhimurium TA1535/pSk1002. Liver homogenates of human fetuses were the most active for the mutagenic activation of aflatoxin B1 (AFB1), followed by 2-amino-3-methylimidazo(4,5-f)quinoline (IQ), and to a lesser extent by 2-amino-6-methyldipyrido(1,2-a:3',2'-d)imidazole (Glu-P-1). The amounts of P-450 HFLa immunochemically determined in human fetal livers correlated highly with the induction of umu gene expression by AFB1 (r = 0.98, n = 5). P-450 HFLa catalyzed the mutagenic activation of AFB1 in a reconstituted system: cytochrome b5 markedly stimulated the activation. Anti-P-450 HFLa antibodies inhibited the mutagenic activation of AFB1 in a dose-dependent manner. These results strongly support the idea that P-450 HFLa is responsible for the mutagenic activation of AFB1 in human fetal livers.

Aflatoxin B1↗
PubMed1984

Glucuronides in bile of rainbow trout (Salmo gairdneri) injected with [3H]aflatoxin B1 and the effects of dietary beta-naphthoflavone.

Rainbow trout Salmo gairdneri were fed a diet containing the mixed-function oxidase system inducer, beta-naphthoflavone or were fed a control diet. For the two respective diets, as much as 50 and 12% of an i.p.-injected dose of [3H]aflatoxin B1 was recovered in the bile. The major product in the bile of beta-naphthoflavone-fed trout was an aflatoxicol-M1 glucuronide, whereas the major product in the control bile was an aflatoxicol glucuronide.

Aflatoxin B1↗
PubMed1981

Enhancement of Aflatoxin B1 induced liver carcinogenesis by portal diversion in the rat.

Conflicting results have been reported on the influence of portacaval anastomosis on liver carcinogenesis. The purpose of this investigation was to study the effect of portal diversion on liver carcinogenesis induced in the rat by a potent chemical liver carcinogen, Aflatoxin B1 (AFB1). Liver tumors appeared earlier and were significantly bigger in rats with shunts than in sham-operated controls. Portal diversion also induced in rats fed AFB1 a splenic atrophy with nearly complete disappearance of Malpighian corpuscles suggesting a profound immunodepression. This might be responsible for the enhancement of liver cancer by portacaval anastomosis in the rats fed AFB1. Thus, the influence of portal diversion on liver cancers appears to be multifactorial.

Aflatoxin B1↗
PubMed2006

Indirect competitive immunoassay for detection of aflatoxin B1 in corn and nut products using the array biosensor.

Because of the potential health risks of aflatoxin B1 (AFB1), it is essential to monitor the level of this mycotoxin in a variety of foods. An indirect competitive immunoassay has been developed using the NRL array biosensor, offering rapid, sensitive detection and quantification of AFB1 in buffer, corn and nut products. AFB1-spiked foods were extracted with methanol and Cy5-anti-AFB1 added to the resulting sample. The extracted sample/antibody mix was passed over a waveguide surface patterned with immobilized AFB1. The resulting fluorescence signal decreased as the concentration of AFB1 in the sample increased. The limit of detection for AFB1 in buffer, 0.3 ng/ml, was found to increase to between 1.5 and 5.1 ng/g and 0.6 and 1.4 ng/g when measured in various corn and nut products, respectively.

Aflatoxin B1↗
PubMed1991

The development of a human cell line stably expressing human CYP3A4: role in the metabolic activation of aflatoxin B1 and comparison to CYP1A2 and CYP2A3.

We have developed a human lymphoblastoid cell line, designated 3A4/Hol, which stably expresses human CYP3A4 cDNA. This cell line exhibited testosterone 6 beta-hydroxylase activity, produced immunologically detectable CYP3A4 protein and was more sensitive to the cytotoxicity and mutagenicity of the carcinogenic mycotoxin aflatoxin B1 (AFB1) than was the parent cell line. The concentration-response for AFB1 cytotoxicity and mutagenicity in 3A4/Hol cells was compared to the responses of isogenic cell lines expressing comparable levels of human CYP1A2 (1A2/Hyg cells) and human CYP2A3 (2A3/Hyg cells). 1A2/Hyg cells were 3- to 6-fold more sensitive than 3A4/Hol cells to AFB1-induced mutation. 3A4/Hol cells were 10- to 15-fold more sensitive to AFB1-induced mutation than 2A3/Hyg cells. The differences in mutagenicity were supported by the relative binding of [3H]AFB1 to cellular DNA.

Aflatoxin B1↗
PubMed1992

Synergism between aflatoxin B1 and oxytetracycline on fatty acid esterification in isolated rat hepatocytes.

The individual and combined effects of aflatoxin B1 (AFB1) and oxytetracycline (OXT) on the synthesis and secretion of triacylglycerols in isolated rat hepatocytes maintained in suspension during 2.5 h were studied. Secretion of triacylglycerols was inhibited by both drugs when administered separately. This inhibition was accompanied by a concomitant elevation of intracellular triacylglycerols only at the highest AFB1 dose tested. Total synthesis of triacylglycerols was not inhibited by AFB1 or by OXT. When the two drugs were simultaneously added to the incubation medium, the AFB1-induced accumulation of intracellular triacylglycerols was no longer observed; the inhibition of secretion was nevertheless identical to that observed with AFB1 alone. Finally, total esterification of palmitate was inhibited by 20% compared to the AFB1-treated cells. These data suggest that OXT inhibits lipid accumulation induced by AFB1 but that this effect is due to an inhibition of total synthesis of triacylglycerols. The mechanism of AFB1's effect and of the interaction between both molecules is discussed.

Aflatoxin B1↗