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Potentiation effect of corn extract on the production of eremofortin C, EC oxidase, and PR toxin by Penicillium roqueforti.

Eremofortin C (EC) and PR toxin are secondary metabolites of Penicillium roqueforti. Their structures are similar and differ only by an alcohol and an aldehyde group at the C-12 position. EC has been demonstrated to be the precursor of PR toxin, and EC is transformed to PR toxin by EC oxidase. These two compounds and EC oxidase are secreted by P. roqueforti in the culture medium, which is usually composed of 15% sucrose and 2% yeast extract. Recently, we discovered that the addition of corn extract to this medium increased the production of EC and PR toxin and the activity of EC oxidase in a coordinative manner. In a time-course study, we found that the peak yield of EC and PR toxin and the maximum activity of EC oxidase in the culture medium containing 7.5% sucrose, 1% yeast extract, and 20% corn extract were increased 6.2, 4.6, and 4.7-fold, respectively, as compared with those obtained in the medium without corn extract. Moreover, corn extract increased the production of EC and PR toxin and the activity of EC oxidase by P. roqueforti in a dose-dependent manner. On the other hand, when the concentrations of sucrose and yeast extract were increased while fixing the ratio of corn extract, we found that the levels of EC and PR toxin and the enzyme activity were decreased concomitantly. We thus conclude that corn extract can enhance the production of EC, PR toxin and EC oxidase by P. roqueforti when grown in a minimal medium and that the potentiation effect of corn extract is suppressed when the fungi are grown in a rich medium.

Alcohol Oxidoreductases↗

Natural occurrence and clastogenic effects of nivalenol, deoxynivalenol, 3-acetyl-deoxynivalenol, 15-acetyl-deoxynivalenol, and zearalenone in corn from a high-risk area of esophageal cancer.

This is the first report of the natural coexistence of a group of Fusarium mycotoxins (nivalenol [NIV], deoxynivalenol [DON], 3-acetyl-deoxynivalenol [3-ADON], 15-acetyl-deoxynivalenol [15-ADON], and zearalenone [ZEN]) in corn from Linxian, China, an area with a high risk of esophageal cancer. Using thin layer chromatography (TLC), high pressure liquid chromatography (HPLC), and gas chromatography (GC), 107 corn samples from Linxian were analyzed. The average levels of NIV and DON were 757 +/- 707 (54-2,760) ng/g and 5,376 +/- 4,460 (360-12,670) ng/g, respectively, with 100% positivity in 24 corn samples consumed as staple food by esophageal cancer patients and their families. Other corn samples collected from five villages in Linxian at different seasons in 1984-1986 also revealed high levels of NIV and DON contamination, with 100% positivity, suggesting that they are consistently and widely present in corn in that area. Levels of 3-ADON and 15-ADON in Linxian corn were 113 +/- 57 and 495 +/- 538 ng/g, respectively. Crude extracts of corn samples collected from esophageal cancer patients' families and the HPLC-purified NIV and DON fractions induced significant chromosome aberrations in V79 cells. Pure toxins of NIV, DON, T-2, and 3-ADON also induced chromosome aberrations in V79 cells at very low concentrations (ng levels/ml medium). Cytotoxic effects were observed at slightly higher concentrations. The levels and kinds of trichothecenes were in positive co-relation with the incidence of esophageal cancer. The data suggest that trichothecenes in food may possibly be associated with esophagitis and esophageal cancer in Linxian.

China↗

Determination of cytotoxic trichothecenes in corn by cell culture toxicity assay.

The great sensitivity of some cell species to toxins has been adapted to a direct biological determination of trichothecene contamination of food and feeds. The murine spleen lymphocyte stimulated by PHA (Phaseolus vulgaris phytohaemagglutinin) appeared to be the most convenient cells because of their particular sensitivity to cytotoxic trichothecenes and the opportunity to translate this cytotoxicity to immunosuppressive hazard, one of the most important concerns for trichothecenes. In this paper, the use of cell cultures was adapted for a survey of corn. The toxins were extracted by aqueous methanol, and the extract was defatted with hexane and purified on a silica gel/Florisil column. This extract was then used for a gas chromatographic (GC) determination and the biological test. The growth of cells was measured by the incorporation of tritiated thymidine (3H Tdr), and the inhibition was expressed by the IC50: concentration of corn extract inhibiting by half the 3H Tdr incorporation. We have tested pure toxins, control corn, corn spiked with T-2 toxin, corn experimentally inoculated with toxigenic Fusarium strains, and naturally contaminated corn. A good correlation exists between IC50 and the T-2 toxin concentration as determined by GC analysis. The response is not affected by the presence of zearalenone or by small amounts of deoxynivalenol. A quantitative evaluation of cytotoxic trichothecenes in corn is valuable in the range of 100 ppb to 10 ppm, expressed as T-2 toxin equivalents. The result is obtained in 48 h.

Animals↗

Effect of supplemental vitamin E and selenium in high moisture corn diets on the incidence of mulberry heart disease and hepatosis dietetica in pigs.

Forty-eight intact male pigs were used to investigate the influence of source of protein supplement, corn moisture content, and supplemental vitamin E-selenium survived the cidence of mulberry heart disease, hepatosis dietetica and associated lesions. Pigs fed soybean meal-high moisture corn diets survived fewer days than pigs fed the other diets. None of the pigs fed torula yeast-dry corn or soybean meal-high moisture corn without supplemental vitamin E-selenium survived the 13 week trial. Supplemental vitamin E-selenium increased survival of pigs. A higher incidence of hepatosis dietetica, myocardial degeneration, skeletal muscle degeneration, and exudative diathesis was observed in pigs fed torula yeast-dry corn or soybean meal-high moisture corn than pigs fed soybean meal-dry corn. Supplemental vitamin E-selenium resulted in a reduction in the incidence of the above lesions by approximately 50% with the exception of hepatosis dietetica. Tissue selenium concentration did not appear to be related to the incidence of the various lesions.

Animal Feed↗

Solvent-efficient thin-layer chromatographic method for the determination of aflatoxins B1, B2, G1, and G2 in corn and peanut products: collaborative study.

An interlaboratory study of a solvent-efficient thin-layer chromatographic (TLC) method for the determination of aflatoxins B1, B2, G1, and G2 was conducted in laboratories located in the United States, France, Tunisia, and Denmark. Eighteen artificially contaminated samples plus blanks of raw peanuts and peanut butter and corn containing varying amounts of aflatoxins B1, B2, G1, and G2 were distributed to participating laboratories. The method consists of elements of the U.S. Food and Drug Administration (FDA), Contaminants Branch (CB) (AOAC Method 968.22) and FDA, Best Foods (BF) (AOAC Method 970.45) methods with reduced requirements for solvents. Participating laboratories used either visual or densitometric techniques during the final determinative step. Statistical analysis of the data was performed to determine or confirm outliers and to compute repeatability and reproducibility of the method using either visual or densitometric techniques for the determinative step. Reported results from laboratories using a densitometer showed that, for corn, the relative standard deviation for repeatability (RSDr) for aflatoxin B1 ranged from 56.6 to 41.7% for contamination levels ranging from 5 to 50 ng/g. For raw peanuts and peanut butter, the RSDr values for aflatoxin B1 ranged from 21.3 to 37.3% and 65.9 to 42.1%, respectively, for the contamination levels ranging from 5 to 25 ng/g. RSDr ranges for aflatoxins B2, G1, and G2 were similar. For reproducibility (R), the RSDR ranges for aflatoxin B1 were 41.7-56.6%, 56.6-84.8%, and 26.4-37.3% for corn, peanut butter, and raw peanuts, respectively. Average recoveries for all aflatoxins at all levels were 95.3, 139.0, and 95.6% for corn, peanut butter, and raw peanuts, respectively. When analysts determined aflatoxin concentrations in corn by visual comparison to standards, the RSDr values for aflatoxin B1 were 47.8-11.4% for contamination levels ranging from 5 to 50 ng/g. For raw peanuts and peanut butter, the RSDr values for aflatoxin B1 were 76.3-12.6% and 33.4-8.8%, respectively, for the contamination levels ranging from 5 to 25 ng/g. RSDr values for aflatoxins B2, G1, and G2 were similar. The RSDR values for aflatoxin B1 were 34.6-90.2%, 45.5-59.3%, and 31.8-78.3% for corn, peanut butter, and raw peanuts, respectively. Average recoveries for all aflatoxins at all levels were 111.0, 157.6, and 92.3% for corn, peanut butter, and raw peanuts, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Aflatoxin B1↗

Differing hepatotoxicity and lethality after subacute trichloroethylene exposure in aqueous or corn oil gavage vehicles in B6C3F1 mice.

Subacute toxicity of trichloroethylene (TCE) was evaluated in male and female B6C3F1 mice using corn oil or aqueous gavage vehicles. Mice received oral doses of TCE five times a week for 4 weeks at 600, 1200 and 2400 mg/kg/day for males and 450, 900 and 1800 mg/kg/day for females. Vehicle control mice were dosed with either corn oil or a 20% aqueous solution of Emulphor. A dose-related increase in lethality occurred in male and female mice receiving TCE in Emulphor but not corn oil during the first week of treatment. Lethality was consistent with central nervous system depressant effects of TCE. After 4 weeks of exposure, body weights were not altered by TCE but liver/body weight ratios were uniformly increased by TCE administered in either vehicle in both sexes. Only male mice treated with TCE in corn oil, however, sustained elevations in serum enzyme levels, accompanied by liver histopathology. TCE in corn oil produced inflammation-associated focal necrosis in 30-40% of the male mice, with increasing severity from low to high dose. Lipid accumulation, as indicated by Oil-Red O staining, was most prevalent in male mice treated with TCE in corn oil but also occurred to a lesser degree in animals receiving either gavage vehicle alone. This study indicates that the type of oral gavage vehicle is an important factor in determining the nature of TCE toxicity.

Administration, Oral↗

Impact of diets containing corn oil or olive/sunflower oil mixture on the human plasma and lipoprotein lipid metabolism.

BACKGROUND: The effects of monounsaturated fatty acids (MUFA) rich diets compared to those that are rich in polyunsaturated fatty acids (PUFA) as well as the effects of an intake of single oils compared to oil mixtures are controversially discussed and results are contradictory. AIM OF THIS STUDY: To evaluate the effects of a plant oil-mixture (olive/sunflower oil; saturated/monounsaturated/polyunsaturated (S/M/P) = 14:69:17) high in oleic acid but also showing a moderate content of polyunsaturated fatty acids (PUFA) in comparison with a single, PUFA rich corn oil (S/M/P = 13:33:54) used in a normal, balanced diet on human plasma and lipoprotein metabolism. METHODS: The double-blind designed study comprised 28 healthy, non-smoking young men aged between 19 and 31 years. After two weeks of adjustment (mixed, balanced diet: 11.6 MJ average, average fat intake approximately 105 g/d), the design included a two week test period in which a diet with 80 g corn oil/d vs a mixture of 68 g olive- and 12 g sunflower oil/d (total 80 g) as the main fat source was given, followed by a crossover after two weeks. Compliance and ingestion of diets were monitored by assessing the fatty acid pattern in LDL and by determination of alpha- and gamma-tocopherol in plasma and LDL. Results Diets were well incorporated due to the significant changes in plasma- and LDL-tocopherol levels and the significant different average ratio of oleic acid to linoleic acid in LDL. The PUFA-rich corn oil diet was able to reduce low density lipoprotein (LDL) cholesterol from adjustment to T2 significantly (p < 0.01), which was also confirmed by a trend after cross over (p=0.15). Total cholesterol (only after cross over at T3), total triglycerides (TG) and very low density lipoprotein (VLDL)-TG were significantly lower at T2 after the corn oil diet than after the mixed oil diet. Total high density lipoproteins (HDL) and HDL cholesterol remained unchanged by both diets. CONCLUSIONS: The results show that during the intervention of two weeks for each diet and the following cross over the corn oil diet had more influence on lipoprotein metabolism than the MUFA-rich diet. The hypocholesteremic effect of the PUFA-rich diet must also be connected with the high amount of unsaponifiable substances, mainly phytosterols in the corn oil.

Adult↗

Effect of dietary hydrogenated corn oil (trans-octadecenoate rich oil) on plasma and hepatic cholesterol metabolism in the hamster.

The effect of dietary hydrogenated corn oil (trans-octadecenoate-rich oil) on plasma cholesterol and triglyceride concentrations was compared with dietary palmitic acid in hamsters given a cholesterol-rich diet. The addition of dietary palmitic acid and hydrogenated corn oil accelerated the increase in plasma VLDL- and LDL-cholesterol levels and plasma triglyceride level induced by dietary cholesterol loading. Dietary cholesterol, palmitic acid and hydrogenated corn oil showed no effect on plasma HDL-cholesterol concentration. A decrease in hepatic LDL receptor activity was seen in animals fed a diet supplemented with cholesterol in combination with palmitic acid or hydrogenated corn oil in comparison with animals fed a diet supplemented with cholesterol alone. Hydrogenated corn oil (trans-octadecenoate-rich oil) appears to potentiate the effect of dietary cholesterol in elevating the plasma VLDL- and LDL-cholesterol levels through the suppression of hepatic LDL receptor activity. trans-Octadecenoate in dietary hydrogenated corn oil may be as atherogenic as dietary palmitic acid due to a suppression of hepatic LDL receptors in the presence of dietary cholesterol loading.

Animals↗

Corn oil and its minor constituents as inhibitors of DMBA-induced chromosomal breaks in vivo.

Inhibitory effects of corn oil and its constituents have been studied against 7,12-dimethylbenz[a]anthracene (DMBA)-induced chromosomal breaks in B6C3F1 female mice using the in vivo bone-marrow micronucleus assay. We tested propyl gallate, alpha-tocopherol and beta-sitosterol as constituents of corn oil. In addition, sunflower oil was tested also to check whether corn oil differs from any other vegetable oil. Corn oil, propyl gallate, beta-sitosterol or sunflower oil were injected i.p. to mice for 2 days at 24-h intervals, prior to injecting DMBA i.p. alpha-Tocopherol was mixed in powdered food and the mice were fed on it for 4 days before receiving DMBA. Bone-marrow samples were collected at various 24-h intervals. About 50-70% reduction in number of micronucleated polychromatic erythrocytes (MNPCE)/500 PCEs were observed in all the treatments wherever corn oil was used. Significant inhibitory effects were noted in treatments with alpha-tocopherol and beta-sitosterol. Sunflower oil also showed an inhibitory effect, similar to that with corn oil.

9,10-Dimethyl-1,2-benzanthracene↗

Effect of gavage vehicle on hepatotoxicity of carbon tetrachloride in CD-1 mice: corn oil versus Tween-60 aqueous emulsion.

This investigation was conducted to evaluate the effect of gavage vehicles on altering the severity of the subchronic hepatotoxicity of carbon tetrachloride (CCl4). Male and female CD-1 mice were gavaged with 0, 1.2, 12, and 120 mg/kg CCl4 in either a corn oil or 1% Tween-60 vehicle once daily for 5 consecutive days per week for 90 days. The study revealed that the hepatotoxicity was greater in the mid- and high-dose groups of mice that had received CCl4 administered in corn oil. Increases in serum enzyme activities were detected in the mid-dose groups of mice that were gavaged with CCl4 in corn oil. The serum enzyme activities were significantly higher in the high-dose groups of animals in which CCl4 was administered in corn oil. Histopathological findings indicated that hepatocellular changes following the administration of CCl4 at the mid- and high-dose levels were more frequent and more severe when CCl4 was given in corn oil than when it was administered in Tween-60. The experimental findings indicate that the no-observed-adverse-effect level from CCl4 exposure was lowered by an order of magnitude (from 12 to 1.2 mg/kg) and that the hepatotoxicity of CCl4 was enhanced in the high-dose treatment groups when corn oil was employed as the gavage vehicle.

Animals↗

Premalignant alterations in rat colonic N1-acetylspermidine levels induced by 1,2-dimethylhydrazine: effects of a high corn oil dietary regimen.

Recently, our laboratory has demonstrated that elevations in the levels of N1-acetylspermidine could be detected in the colonic mucosa of rats after administration of 1,2-dimethylhydrazine for 15 weeks, i.e., before the development of colon tumors. Since prior studies have indicated that diets high in fat, particularly unsaturated fat, promote the development of dimethylhydrazine-induced tumors, it was of interest to examine the effect of a corn oil dietary regimen (20% by weight) on colonic N1-acetylspermidine levels in this model of colonic adenocarcinoma. Four groups of rats were used in these studies: chow, chow + carcinogen, corn oil and corn oil + carcinogen. The carcinogen groups received weekly s.c. injections of 1,2-dimethylhydrazine (20 mg/kg body wt) for 15 weeks, while the control groups received diluent. 1 week after the last injection, animals from each group were killed, and their proximal and distal colons were resected, examined and compared with respect to polyamine levels, including N1-acetylspermidine, as well as the activities of ornithine decarboxylase, spermidine N1-acetyltransferase, and polyamine oxidase. In view of previous studies which suggested that N1-acetylspermidine levels may be elevated in the urine of patients with various malignancies, it was also of interest to examine and compare the urinary levels of this acetylated polyamine in animals from each group. The results of these experiments demonstrated that: (1) the levels of N1-acetylspermidine in the distal colonic segment were found to be increased approx. 25 and 80% in the chow + carcinogen and corn oil + carcinogen groups, respectively, compared to their control counterparts; (2) the activities of spermidine N1-acetyltransferase in the distal colonic segments of chow + carcinogen and corn oil + carcinogen animals were increased 1.5- and 2-fold, respectively, compared to control values; (3) dimethylhydrazine administration did not affect the levels of this acetylated polyamine or spermidine N1-acetyltransferase activities in the proximal colon, but, in general, did increase the levels of putrescine and spermidine as well as ornithine decarboxylase activities in both colonic segments of animals fed chow or corn oil diets; and (4) elevated urinary levels of N1-acetylspermidine did not appear to be a reliable 'premalignant' marker in this experimental model of colonic adenocarcinoma.

1,2-Dimethylhydrazine↗

Evaluation of oils and microbial pathogens for control of lepidopteran pests of sweet corn in New England.

Vegetable and mineral oil, Beauveria bassiana (Balsamo) and Bacillus thuringiensis subsp. kurstaki Berliner were evaluated for control of Ostrinia nubilalis (Hübner) (Lepidoptera: Pyralidae), Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) and Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) in sweet corn (Zea mays L.). Field experiments in Maine and Massachusetts during 1993 and 1994 evaluated oils and pathogens singly or in combinations, using a single application directly to the top of the silk channel, immediately after pollination. Mineral oil alone provided equal (1993) or better (1994) control compared with corn oil. In both years, mineral or corn oil plus B. thuringiensis resulted in 93-98% marketable ears, compared with 48-52% marketable ears in untreated plots. In three factorial experiments with B. bassiana, B. thuringiensis and corn oil, B. bassiana at 5 x 10(7) conidia per ear provided little or no control while B. thuringiensis and corn oil provided significant though not always consistent control of all three species. The combination of B. thuringiensis and corn oil provided the largest and most consistent reduction in numbers of larvae and feeding damage to ears.

Animals↗

Digestibility of cocoa butter and corn oil and their influence on fatty acid distribution in rats.

The comparative bioavailability of cocoa butter (a predominantly saturated fat) and corn oil (a predominantly unsaturated fat) was determined in male Sprague-Dawley rats by analysis of total fecal lipids following ad libitum feeding of purified diets containing 5, 10 and 20% cocoa butter or corn oil for 2 wk. Fecal lipid elimination was significantly increased (P less than 0.05) in each cocoa butter group when compared with the corresponding corn oil group, resulting in lower digestibility coefficients for cocoa butter (59-72%) than for corn oil (93-97%). Body weight gain and food intake data were similar among all treatment groups. Fecal fatty acid profiles in rats fed corn oil diets consisted primarily of 27-34% palmitic acid (16:0), 22-32% stearic acid (18:0) and 25-37% oleic acid (18:1). Palmitic, oleic and linoleic acids were also the primary fatty acids stored in epididymal fat tissue from corn oil-fed rats. In contrast, fecal fatty acids in animals fed cocoa butter diets consisted of 31-37% palmitic acid and 58-64% stearic acid; oleic acid was the major fatty acid stored in epididymal fat tissue. These results indicate that the decreased digestibility of cocoa butter is largely a result of its fatty acid composition. This reduced bioavailability of cocoa butter may be at least partially responsible for its previously described neutral effect on serum cholesterol.

Adipose Tissue↗

Diets containing corn oil, coconut oil and cholesterol alter ventricular hypertrophy, dilatation and function in hearts of rats fed copper-deficient diets.

Cardiac hypertrophy and function were evaluated in rats fed diets containing deficient, marginal or adequate levels of copper. The fat concentration of the diets was either 10 g/100 g corn oil, 10 g/100 g coconut oil or 10 g/100 g coconut oil + 1 g/100 g added cholesterol. Left ventricular (LV) wall thickening of hearts in rats fed copper-deficient diets was characterized by greater (P < 0.05) LV free wall width, regardless of dietary fat type, and greater intraventricular septum width in the rats fed corn oil. Rats fed the copper-deficient diet with coconut oil + cholesterol had LV chamber volumes that were twofold larger than those of rats fed the copper-deficient diet with coconut oil or corn oil. Copper deficiency reduced LV chamber volume only in rats fed coconut oil + cholesterol. Cardiac LV end diastolic pressure in rats fed copper-deficient diets was twofold larger than in copper-adequate and copper-marginal groups fed corn oil or coconut oil. Hearts from rats fed the copper-deficient diet with corn oil compared with those from rats fed the copper-deficient diet with coconut oil + cholesterol had greater right ventricular (RV) and LV end diastolic pressures, LV pressures and LV and RV maximal rates of positive pressure development. Our data suggest that cardiac adaptations in rats fed copper-deficient diets are influenced by dietary fat type: 1) hearts of rats fed the copper-deficient diet with corn oil were concentrically hypertrophied, whereas cardiac contractility was maintained in the presence of high preload; 2) preload and contractility in hearts of coconut oil-fed rats was greater than cardiac response to cholesterol addition to the coconut oil diet; 3) hearts in copper-deficient rats fed coconut oil + cholesterol exhibited eccentric hypertrophy and ventricular dysfunction.

Animals↗

Neoplasms observed in untreated and corn oil gavage control groups of F344/N rats and (C57BL/6N X C3H/HeN)F1 (B6C3F1) mice.

Control data on F344/N rats and (C57BL/6N X C3H/HeN)F1 (B6C3F1) mammary tumor virus-free mice from the National Toxicology Program (NTP) were examined to determine if animals receiving corn oil by gavage showed tumor incidences that differed from those of untreated control animals. Analyses of these data were adjusted for interlaboratory variability, time-related trends, and supplier effects. Two biologically significant effects were found: Male F344/N control rats receiving corn oil by gavage showed a higher (P less than .05) incidence of pancreatic acinar cell adenoma and a lower (P less than .001) incidence of leukemia (primarily mononuclear cell leukemia) than did the corresponding untreated controls. The increased incidences of pancreatic acinar cell adenoma seen in male rats administered corn oil by gavage were associated with elevated body weights observed in these animals relative to untreated controls. Female F344 rats and male and female B6C3F1 mice showed little or no evidence of a difference in tumor incidence between corn oil gavage-treated and untreated controls. A review of nearly 300 carcinogenesis studies done by the National Cancer Institute (NCI) and the NTP revealed that there were no corn oil gavage studies in which increased incidences of pancreatic acinar cell tumors or leukemia in male F344/N rats were the sole evidence of the carcinogenicity of a test chemical. Thus use of corn oil appears to have little impact on the interpretation of NCI-NTP carcinogenicity studies.

Animals↗

Pharmacokinetics of ipriflavone and metabolites after oral administration of a corn-oil suspension relative to the Osteofix tablet.

Ipriflavone (IP) is a derivative of naturally occurring isoflavones and is marketed as Osteofix for the treatment of osteoporosis in Europe. IP has poor aqueous solubility, and the Osteofix compressed tablet has poor and variable bioavailability (F ). IP is incompletely absorbed after oral administration and is converted to five major metabolites (M1, M2, M3, M4, and M5). It is also further converted to metabolites M6 and M7 to a very small extent. The metabolites, especially M2 and M5, also have activity. A pilot study was conducted in healthy male volunteers that showed an 8- to 20-fold increase in the IP bioavailability after administration of Osteofix tablets in the fed state relative to the fasting state. A four-way crossover study was conducted in 16 healthy male volunteers, receiving Osteofix in fed state and 50, 100, and 200 mg of IP corn-oil suspension in fasted state. All IP administrations were safe and well tolerated. There was a reduction in the IP plasma level variability after 100-mg corn-oil administration as compared with that for the tablet. There was an increased relative F after the suspension, which was such that the 50-mg IP corn-oil suspension yielded similar levels as the 200-mg tablet. M5 was the major metabolite, consistent with earlier reports. The area under the curve to the last measured time point (AUC ( t ) ) levels were lower for M5, M3, and M2; higher for M1 and M2; and similar for IP after 50-mg corn-oil administration, as compared with the values for the tablet. This result may partially be explained by differences in the half-lives. Absorption/formation of M2 was delayed. The metabolite formation, except for M1 and M5, decreased with increased doses, which was accompanied by the prolonged half-life of IP and nonproportional increase in the IP AUC ( t ). This result may be due to autoinhibition of IP metabolism, because IP is an inhibitor of CYP3A4, and the metabolism of IP may be partly CYP3A4 mediated. Osteofix F may be improved by formulations that increase solubility, such as the corn-oil suspension. Although equivalent IP exposure from the tablet may be achieved at much lower overall doses because of the improved F by the corn-oil suspension, higher doses may require reconfirmation of safety and efficacy, given the differences in metabolic profiles obtained at higher doses.

Administration, Oral↗

Intake of different concentrations of sucrose and corn oil in preweanling rats.

To investigate the orosensory control of ingestion in preweanling rats, we infused one of the following liquids continuously through anterior sublingual intraoral catheters for 20 min: sucrose solutions (5, 10, 20, and 40%) and corn oil emulsions (6.25, 12.5, 25, 50, and 100%). Pups were tested at 7, 14, 21, and 28 days of age. Each pup was tested only once. Intake of sucrose and of corn oil became increasingly correlated with concentration from 7 to 21 days. Sucrose elicited more intake than water by day 7, whereas corn oil did not until day 14. Low concentrations of sucrose had differential effects on intake by day 14, but low concentrations of corn oil emulsions did not have differential effects on intake until day 21. At all ages, the peak intake of sucrose was significantly larger than the peak intake of corn oil. These differences are probably not based on prior experience because each test of ingestion represented a first exposure to the stimulus. Thus we suggest that the differences are due to the maturation of the orosensory control of ingestion by sucrose and corn oil.

Aging↗

Blood pressure in spontaneously hypertensive rats fed butterfat, corn oil, or fish oil.

Dietary fats have been shown to influence blood pressure in humans and animal models of hypertension. The ability of a particular fat to modulate arterial pressure appears to depend on its fatty acid profile rather than its degree of saturation or unsaturation. Little is known about the effects of specific dietary fats of animal origin on blood pressure. We tested the concurrent effects of both calcium and dietary fat on blood pressure development in the spontaneously hypertensive rat. Sixty animals were fed diets containing butterfat, fish oil, or corn oil from 3-26 weeks of age. Each diet among the three oils was further modified to contain either 0.25% or 2.0% of the diet as calcium. All six diets provided 18% of the diet (36% of the calories) as fat. The polyunsaturated-to-saturated fat ratio was 0.07, 0.84, and 4.54 for butterfat, fish oil, and corn oil, respectively. Fish oil consumption resulted in lower blood pressures compared with butterfat (p less than 0.036) or corn oil (p less than 0.0009). Similarly, butterfat feeding resulted in lower blood pressures when compared with corn oil (p less than 0.054). Supplementing the diet with calcium decreased blood pressure in both the butterfat and corn oil diets. When butterfat diets were supplemented with calcium, the resulting blood pressures did not differ significantly from those obtained with the two fish oil diets. It is concluded that butterfat, though highly saturated, is associated with less of an increase in the spontaneously hypertensive rat's blood pressure than is corn oil, which is highly unsaturated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗