Administered Corn Oil Research Articles

Male rats exposed to linuron in utero exhibit permanent changes in anogenital distance, nipple retention, and epididymal malformations that result in subsequent testicular atrophy.

Prenatal exposure to the herbicide linuron, a weak androgen receptor antagonist, has been shown to perturb androgen-dependent male rat reproductive development as evidenced by slight decreases in anogenital distance (AGD), increased retention of areolae/nipples, and induction of epididymal malformations in combination with testicular atrophy in the adult rat over dose levels ranging from 12.5 to 100 mg/kg/day. Studies were undertaken to determine whether linuron-mediated changes in AGD and nipple retention are permanent, whether linuron is a direct testicular toxicant, and if there was an association between areola/nipple retention and malformations. Pregnant rats were administered corn oil vehicle or linuron by gavage at 0 or 50 mg/kg/day (n = 8 controls, 20 treated) from gestation days 12 to 21. Male offspring were necropsied on postnatal days (PND) 35 and 56. Linuron-exposed male rats exhibited a significant (8%) decrease in AGD on PND 1 and a similar decrease was also observed on PND 56. Linuron-exposed male rats displayed an increase in areola retention on PND 13, as evidenced by 0.6 +/- 0.5 and 3.3 +/- 0.4 areolae per rat in the control and exposed groups, respectively. Male rats displayed a significant increase in nipple retention on PND 35 and 56 (collectively) of 0 +/- 0.5 and 1.7 +/- 0.3 nipples per rat in control and exposed groups, respectively. On PND 35, 4/51 rats (3/9 litters) from linuron-treated dams displayed enlarged testes in combination with malformed epididymides. Epididymal malformations were observed in 19/51 rats (6/9 litters) in the linuron-exposed dose group. On PND 56, grossly enlarged and edematous testes were seen in 16/56 linuron-exposed rats (6/9 litters). Epididymal lesions were observed in 23/58 rats (6/9 litters). Microscopically, all linuron-exposed animals that exhibited a testicular lesion on PND 56 also displayed an epididymal lesion. These lesions were not seen in control animals. Approximately 25 and 60% of the male offspring that had malformations of the epididymis and vas deferens did not exhibit either areolae on PND 13 or nipples at necropsy, respectively. These data indicate that in utero linuron exposure to 50 mg/kg/day results in permanent changes in AGD and nipple retention in male rats. Moreover, these findings indicate that linuron-induced testicular atrophy, which is observed in adult rats, is secondary to increased intratubular pressure resulting from obstruction of testicular fluid outflow subsequent to malformation of the epididymides. These data also suggest that although linuron-mediated retention of areolae on PND 13 and nipples at necropsy may be suggestive of altered testosterone-mediated reproductive development seen in adult rats, these endpoints are not predictive.

The benchmark approach applied to a 28-day toxicity study with Rhodorsil Silane in rats: the impact of increasing the number of dose groups

The OECD study design, aimed at obtaining a no-observed-adverse-effect level (NOAEL), may be suboptimal for deriving a benchmark dose. Therefore the present subacute (28-day) study was carried out to evaluate a multiple dose study design and to compare the results with the common OECD design. Seven groups of 10 female rats each were intragastrically administered corn oil without (controls) or with 50, 150, 300, 450, 600 or 750 mg Rhodorsil Silane/kg body weight/day, once daily (7 days/week) for 4 weeks. From the complete dataset, two subsets were selected, one representing a study design with seven dose groups of five animals (7×5 design), the other representing a study design with four dose groups of 10 animals (4×10 design). Under the conditions of the present study, the NOAEL for Rhodorsil Silane 198 was assessed at 50 mg/kg body weight/day, based on the data of the 4×10 design. The benchmark approach resulted in a benchmark dose of 19 mg/kg body weight/day, based on the data of the 7×5 design. Comparison of the results demonstrated that the multiple dose (7×5) design led to a more reliable result than the OECD (4×10) design, despite the smaller total number of animals. The dose–response analysis showed that at “the NOAEL” the effect on relative spleen weight was larger than 10%, illustrating that at the NOAEL, adverse effects may occur.

The effect of trimetazidine on intrahepatic cholestasis caused by carmustine in rats

This study investigated the effect of trimetazidine (TMZ), known as an anti-oxidant agent, on intrahepatic cholestasis caused by Carmustine (BCNU) in rats. Rats were assigned into four groups. The first group (Saline) consisted of 12 rats, which were injected with 2 ml/kg of saline intraperitoneally (IP) 48 h before the study. The second group (corn oil group, n=15), which were injected with 2 ml/kg of corn oil IP 48 h before the study. The third group (BCNU group, n=16), which were injected with 2 ml/kg of corn oil+25 mg/kg BCNU IP 48 h before the study. The fourth group (TMZ group, n=12), which were injected with 2.5 mg/kg per day of TMZ IP, administered at the same hour of the day as a single-dose. Twelve hour after the first dose of TMZ, corn oil 2 ml/kg+BCNU 25 mg/kg IP were injected, and the rats were included in the study 48 h after the administration of corn oil+BCNU. Following a pentobarbital anaesthesia, abdomen was opened with incision, a cannula was placed into the channel of choledocus, and the amount of bile was measured per hour. Then intracardiac blood sample was taken, and consequently centrifuged to obtain the plasma. Finally, the rats were killed with cervical dislocation, and their livers were removed and weighted. In addition to histopathological examination of liver, the levels of malon dialdehyde (MDA), oxidised glutation (GSSG), and reduced glutation (GSH) were detected. Also the osmolality of bile and plasma was estimated in mOsm/kg. As a result, the biliary flow was seen to decrease in BCNU group ( P<0.005), but to be normal in TMZ group. The serum level of conjugated biluribin was higher in BCNU group compared to other groups ( P<0.05 for each). Although the level of total glutation was lower ( P<0.005) in TMZ group, GSH/GSSG ratio was normal. These findings suggest that TMZ has a protective effect on intrahepatic cholestasis caused by BCNU.

Developmental Toxicity Study of Orally Administered Resorcinol Bis-Diphenylphosphate (RDP) in Rabbits

Fyrolflex resorcinolbis-diphenylphosphate (RDP) is a nonhalogenphosphate ester product that is widely used as a flame retardant for petrochemicalplastics and high-temperature lubricant additive applications. The potential developmental toxicity of RDP was evaluated in rabbits. Groups of 27 sperm-positive New Zealand white rabbits (Hazelton Research Products Inc., Denver, PA) were administered graded concentrations of 50, 200, or 1000 mg/kg/day of RDP in corn oil. A vehicle control group of equal size was administered corn oil alone. Rabbits were dosed daily (1.5 ml/kg) on gestationdays 6 to 28 and sacrificed on gestationday 29. The fetuses were removed by cesarean section and examined for gross external, visceral, cephalic, and skeletal anomalies. No treatment-related clinical signs of toxicity were observed. No treatment-related effects in maternal food consumption, body weight, body weight gain, or on uterus, liver, kidney, and spleen weights were detected. Fetal viability and body weight, as well as developmental end points were also unaffected by treatment. Accordingly, exposure of pregnant rabbits to doses ranging from 50 to 1000 mg/kg/day of RDP during the periods of major organogenesis and histogenesis did not result in any biologically significant toxic or teratogenic/developmental effect in the dams or fetuses.

PHENYLSILSESQUIOXANE FLUID: DEVELOPMENTAL TOXICITY STUDIES IN RATS AND RABBITS FOLLOWING ORAL ADMINISTRATION

Phenylsilsesquioxane fluid (PSF) is used widely in the personal care industry and is a common component of skin and oral care products. The potential developmental toxicity of PSF was evaluated in rats and rabbits. Groups of 25 sperm-positive Sprague-Dawley rats (Taconic Farms) and 15 sperm-positive New Zealand White rabbits (HRP) were administered dose levels of 50, 500, or 1000 mg/kg PSF in corn oil. Vehicle control groups of equal size were administered corn oil alone. Rats were dosed daily (5 ml/kg) on gestation d 6?15 and sacrificed on gestation d 20, while rabbits were dosed daily (1.5 ml/kg) on gestation d 6?18 and sacrificed on gestation d 29. The fetuses were removed by cesarean section and examined for gross external, visceral, cephalic, and skeletal anomalies. No treatment-related clinical signs of toxicity were observed. No marked effects upon maternal food consumption, body weight, body weight gain, or uterus or liver weight were detected. Fetal viability and body weight, as well as developmental endpoints, were unaffected by treatment. Accordingly, exposure of pregnant rats or rabbits to 50, 500, or 1000 mg/kg of PSF during the period of major organogenesis did not result in any biologically significant adverse or teratogenic effects in the dams or fetuses.

Influence of Corn Oil and Diet on Reproduction and the Kidney in Female Sprague-Dawley Rats

The purpose of this study was to investigate the influence of corn oil administration on gestation, parturition, and lactation in rats, in conjunction with diets differing in composition of nutrients. Rats were divided into two groups, each fed different commercial pellets for rodents, CA-1 or CE-2, different from each other mainly in the source of protein. Female Sprague-Dawley rats in both diet groups were administered 0 (untreated control), 2, or 10 ml corn oil/kg body weight by gavage during the premating period (2 weeks), the mating period, the gestation period, and the lactation period (until day 3 of lactation). Food consumption of both the 10 ml/kg corn oil groups was significantly reduced throughout the study. Body weight gain in the 10 ml/kg corn oil group fed the CA-1 diet was significantly reduced on days 0 through 4 of lactation. Neither mating nor fertility indices were affected, and no clinical signs were observed during the gestation period in any groups. Several dams in the 10 ml/kg corn oil group fed the CA-1 diet, however, showed abnormal conditions after parturition, and three dams became moribund. Pup viability was also reduced in this group. Histopathologic examination of the kidneys of dams in the 10 ml/kg corn oil group fed the CA-1 diet revealed severe lesions in the proximal tubular epithelium, i.e., necrosis and fatty degeneration. Females in any group fed the CE-2 diet showed neither abnormal condition after parturition nor any severe lesions in the kidney. These data show that the combination of corn oil and diet with a particular constitution may cause adverse effects on the renal tubules in pregnant and/or lactating rats, suggesting that corn oil gavage as a vehicle can be a confounding factor in the reproductive toxicity studies, depending on the diet.

Screening of lipase inhibitors from marine algae.

The possible presence of an inhibitor of pancreatic lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) was screened in 54 marine algae. An active inhibitor, caulerpenyne, was purified from an extract of Caulerpa taxifolia, using ethyl acetate extraction, followed by successive chromatographies on ODS and silica gel columns. The purified inhibitor was identified by thin-layer chromatography, infrared and nuclear magnetic resonance spectroscopy. Caulerpenyne competitively inhibited lipase activities using emulsified triolein and dispersed 4-methylumbelliferyl oleate (4-MU oleate) as substrates. The concentrations producing 50% inhibition against triolein and 4-MU oleate hydrolysis were 2 mM and 13 microM, respectively. In vivo, oral administration of corn oil with or without caulerpenyne to rats demonstrated a reduced and delayed peak plasma triacylglycerol concentration with caulerpenyne.

Dietary fatty acids are possible key determinants of cellular retinol-binding protein II gene expression.

We previously found that dietary unsaturated fatty acids increase cellular retinol-binding protein type II (CRBP II) mRNA and its protein levels in rat jejunum. To obtain insight into mechanisms for its gene induction, we investigated the effect of depletion of dietary fat on CRBP II mRNA levels and we further examined whether dietary retinol is necessary for dietary fat-induced CRBP II gene expression. Feeding the fat-free diet, which contained a sufficient amount of vitamin A, repressed CRBP II mRNA accumulation by 50% within 1 day, and this low level was sustained over the next 9 days. Parallel to the decreased CRBP II mRNA level, the peroxisomal proliferator-activated receptor-alpha (PPAR-alpha) mRNA level in rat jejunum was decreased by long-term (7 days) feeding of an isocaloric low-fat diet compared with the control. Oral administration of corn oil in the animals fed vitamin A-free diet elicited approximately threefold accumulation of CRBP II mRNA within 6 h. However, the administration of 9-cis-retinoic acid brought about no accumulation of CRBP II mRNA. Even when rats were vitamin A-deficient, oral administration of corn oil, but not 9-cis-retinoic acid, caused an increase in jejunal CRBP II mRNA level. These results suggest that CRBP II gene expression in rat jejunum may be regulated predominantly by dietary fatty acids but little by dietary retinoids.

Thalidomide promotes metastasis of prostate adenocarcinoma cells (PA-III) in L-W rats.

Two contradictory actions have been ascribed to thalidomide relative to tumor metastasis: immunosuppression and anti-angiogenesis. The latter effect was determined with basic fibroblast growth factor in a rabbit cornea micropocket assay system. The prostate adenocarcinoma (PA-III) transplanted tumor line in Lobund-Wistar (L-W) rats produces a tumor at the subcutaneous implant site from which tumor cells metastasize uniformly only through lymphatic channels through the heart to the lungs in which secondary tumors develop. L-W rats were implanted with PA-III cells and administered, by gavage, thalidomide (50 mg/kg body wt per day) in corn oil. Control rats with PA-III cells were administered corn oil. Autopsy examinations on day 30 revealed that the thalidomide-treated rats developed more metastatic tumor foci in the lungs than in the controls.

Toxic Interactions Between Fungicides That Inhibit Ergosterol Biosynthesis and Phosphorothioate Insecticides in the Male Rat and Bobwhite Quail (Colinus virginianus)

The potential for toxic interactions between ergosterol biosynthesis-inhibiting fungicides (EBIFs), used in U.S. agriculture or clinically, and phosphorothioate insecticides was assessed in adult male rats and adult male bobwhite quail (Colinus virginianus) by measuring inhibition of plasma butyryl cholinesterase (BChE) following fungicide and insecticide treatment. Male Sprague-Dawley rats (300 g) were administered corn oil or the following EBIFs: propiconazole (400 mg/kg/day), vinclozolin (400 mg/kg/day), clotrimazole (100 mg/kg/day), or ketoconazole (100 mg/kg/day) for 3 days by oral gavage. Forty-eight hours following the final dose, a single bolus of parathion (0.4 mg/kg in corn oil) or malathion (150 mg/kg in corn oil) or corn oil alone was given po. The rats were terminated 12 hr following parathion or 4 hr following malathion dosing. Significant (p < 0.05) inhibition of BChE was observed with parathion and malathion only following clotrimazole treatment. In contrast, when a similar experiment was performed in bobwhite quail dosed with 12 mg/kg malathion following EBIF treatment, significant BChE inhibition was observed following treatment with vinclozolin or ketoconazole, but not with propiconazole or clotrimazole. Induction of cytochrome P450 in rat and quail liver by EBIFs was accompanied by enhanced oxidative desulfuration of malathion, parathion, and diazinon to toxic oxon products. Increased detoxication via oxidative dearylation/esterolytic clevage also occurred. However, while enhanced acute in vivo insecticide toxicity was observed in both species with a number of EBIF-phosphorothioate combinations, EBIF-induced oxidative activation of phosphorothioates by liver microsomes in vitro was not a good predictor of this effect.

Teratologic Evaluations of N,N-Diethyl-m-toluamide (DEET) in Rats and Rabbits

Teratologic Evaluations of N,N-Diethyl-m-toluamide (DEET) in Rats and Rabbits. Schoenig, G. P., Neeper-Bradley, T. L., Fisher, L. C., and Hartnagel, R. E. (1994). Fundam. Appl. Toxicol. 23, 63-69.The potential for DEET to produce developmental toxicity was evaluated in Charles River CD rats and New Zealand White rabbits. Rats were administered undiluted DEET by gavage on Gestational Days (gd) 6-15 at dosage levels of 0, 125, 250, and 750 mg/kg/day. Rabbits were administered undiluted DEET by gavage on gd 6-18 at dosage levels of 0, 30, 100, and 325 mg/kg/day. Group sizes were 25 females per group for rats and 16 females per group for rabbits. Control rats and rabbits were administered corn oil at the same dosage volumes administered in the high-dose DEET groups. In rats, maternal toxicity in the form of clinical signs including two deaths and depressed body weight and food consumption was observed at the high-dose level of 750 mg/kg/day. Rat fetal body weights per litter also were reduced at 750 mg/kg/day. In rabbits, maternal toxicity in the form of depressed body weight and food consumption was observed at the high-dose level of 325 mg/kg/day. No maternal toxicity was observed at the low- or mid-dose groups for rats or rabbits. With the exception of the reduced fetal weights in rats at 750 mg/kg, there was no evidence of fetal toxicity, no effects on any of the gestational parameters, nor were there any treatment-related increases in external, visceral, or skeletal variations or malformations in the offspring from the rats and rabbits from these studies.

N-3 versus n-6 Fatty Acid Incorporation into the Phospholipids of Rat Heart Sarcolemma. A Comparative Study of Four Different Oil Diets

The fatty acid (FA) composition of the phospholipids of rat heart sarcolemma was studied after a 10-week feeding period of diets containing 10% of each of coconut oil, corn oil, linseed oil, and fish oil in comparison to a low fat diet. The major modifications observed were the following: (1) a general increase of the n-6 FA family upon corn oil administration; (2) a dual effect of linseed oil in increasing 18:2 n-6 (more than did corn oil) and decreasing 20:4 n-6 and 22:4 n-6. At the same time n-3 FA increased significantly; and (3) a significant fall in the n-6 FA following fish oil, and a marked rise in the n-3 Fa. The 10-fold increase in 22:6 n-3 supports the hypothesis of an inhibition of arachidonate synthesis, as well as that of the competition for the incorporation sites of phospholipids. In general, the n-3 FA diets produced the replacement of the n-6 FA by the n-3 FA in membrane phospholipids, and led to a significant increase of the double bond index (DBI).

Effect of frequency of isothiocyanate administration on inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced pulmonary adenoma formation in A/J mice

The abilities of phenethyl isothiocyanate (PEITC) and 6-phenylhexyl isothiocyanate (PHITC) to inhibit 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenicity, when administered by a standard four-dose protocol or by a single-dose protocol, were determined. Corn oil or isothiocyanates were administered once or for four consecutive days by gavage, with the final (or single) administration of corn oil or inhibitor occurring 2 h prior to a single i.p. injection of NNK (10 μmol/mouse). Sixteen weeks following NNK administration, the experiment was terminated and pulmonary adenomas were quantitated. Pretreatment with PEITC at a dose of 5 μmol or PHITC at a dose of 0.2 μmol resulted in significant reductions of tumor multiplicity compared to control, regardless of whether each isothiocyanate was administered once or four times. For both isothiocyanates, there were no statistically significant differences between dosing frequencies in inhibitory effects on tumor multiplicities and tumor incidences. Furthermore, the results achieved following a single pretreatment with either isothiocyanate were in good agreement with previous results obtained utilizing the four-dose protocol. Thus, it appears that most or all of the inhibitory potential of the four-dose protocol is due to the final dose of isothiocyanate.

Role of Cholecystokinin in Pancreatic Bicarbonate Secretion in Dogs

We investigated the effects of endogenous and exogenous cholecystokinin (CCK) on pancreatic exocrine secretion, in particular that of bicarbonate. In six dogs prepared with gastric cannulas and Thomas duodenal cannulas, intraduodenal administration of corn oil (Lipomul) incubated with hog pancreatic enzymes significantly increased pancreatic secretion of both bicarbonate and protein. Increase in pancreatic secretion of both bicarbonate and protein was accompanied by the increase in plasma CCK concentration. However, the increase in bicarbonate as well as protein secretion was blocked by proglumide, a CCK antagonist, given intravenously. In contrast, intraduodenal infusion of undigested Lipomul failed to stimulate the pancreatic exocrine secretion or release of endogenous CCK. These observations indicate that endogenous CCK plays an important role in secretion of both bicarbonate and protein stimulated by digested corn oil. In a group of four dogs with pancreatic fistulas, intravenous infusion of CCK potentiated the stimulatory effect of secretin on pancreatic bicarbonate secretion. The stimulatory effect as well as potentiating effect of CCK on pancreatic bicarbonate secretion was blocked by infusion of proglumide. We conclude that endogenous CCK plays a significant role in fat-stimulated pancreatic secretion, and it is apparent that both endogenous CCK and secretin are equally important for stimulation of pancreatic bicarbonate secretion, which results from potentiation of the action of the two hormones.

Variations in Total Bile Acid Concentration in Serum of Dogs after a Test Meal

The purpose of this study was to examine the variations in total serum bile acid (SBA) concentration following oral administration of corn oil (3.0 ml per kg body weight) to six fasted healthy dogs using a previously validated automated method (JENSEN, 1991) for the determination of SBA concentration. The preprandial SBA concentration was 2.22 mumol/l (0.64-6.41 mumol/l) (median, 0.025-0.975 fractiles). In the 2-6 hours postprandial period, all the SBA concentrations were significantly different from the preprandial value, but not significantly different from each other. For the total 2-6 hours postprandial period the SBA concentration was 7.89 mumol/l (1.39-22.24 mumol/l). From these results it may be suggested that the reference range for the preprandial SBA concentration in dogs is 0.64-6.41 mumol/l, and that the reference range for the postprandial SBA concentration in a blood sample obtained 2 hours after oral administration of corn oil is 1.39-22.24 mumol/l.

Effect of Truncal Vagotomy on Cholecystokinin Release, Gallbladder Contraction, and Gallbladder Sensitivity to Cholecystokinin in Humans

The present study was undertaken to investigate the gastric and intestinal phase of stimulation of postprandial gallbladder contraction and endogenous cholecystokinin secretion in patients with truncal vagotomy and pyloroplasty. Gallbladder emptying, measured by cholescintigraphy, and endogenous cholecystokinin secretion, measured by radioimmunoassay, were studied after both intragastric and intraduodenal administration of corn oil. In addition, the gallbladder responsiveness to cholecystokinin was investigated by infusion of stepwise increasing doses of exogenous cholecystokinin. In the 6 patients with truncal vagotomy, plasma CCK and gallbladder responses to intraduodenal fat were significantly delayed compared to normal subjects. In contrast, the onset of the plasma cholecystokinin increase and gallbladder emptying after intragastric fat was significantly earlier in the vagotomized patients compared with the normal subjects. In the normal subjects, plasma cholecystokinin and gallbladder responses to intragastric fat were significantly lower during the first 25 min after stimulation compared with the results after intraduodenal fat, whereas in the patients with truncal vagotomy and pyloroplasty, no differences in plasma cholecystokinin and gallbladder responses were found according to the site of fat stimulation. The gallbladder-emptying response to exogenous cholecystokinin increased significantly in patients who had undergone truncal vagotomy. It is concluded (a) that truncal vagotomy with pyloroplasty influences the timing but not the magnitude of fat-stimulated gallbladder contraction and endogenous cholecystokinin secretion; and (b) that the sensitivity of the gallbladder to endogenous and exogenous cholecystokinin is significantly increased in patients with truncal vagotomy.

Role of the gastric phase in fat‐induced gallbladder contraction and cholecystokinin secretion in humans

The present study was undertaken to investigate the role of the gastric phase of fat-induced gallbladder contraction and endogenous cholecystokinin (CCK) secretion in humans. Gallbladder emptying, measured by cholescintigraphy, and endogenous CCK secretion, measured by radioimmunoassay, were studied in healthy subjects after both intragastric and intra-intestinal administration of corn oil. In addition, patients with partial gastrectomy were investigated to study the effect of accelerated gastric emptying. In the healthy subjects, intragastric administration of fat resulted in a significantly (P less than 0.05) later increase in plasma CCK levels (20 +/- 2 min) compared to intraintestinal fat (5 +/- 1 min). Similarly, the onset of gallbladder emptying was significantly (P less than 0.05) delayed after intragastric fat (20 +/- 2 min) compared to intestinal fat (10 +/- 1 min). In the healthy subjects the integrated plasma CCK response to intragastric fat was significantly (P less than 0.005-P less than 0.01) reduced from 10 to 30 min. In the patients with partial gastrectomy the rise in plasma CCK (10 +/- 1 min) and the onset of gallbladder emptying (15 +/- 2 min) were in the same range after intra-intestinal and intragastric fat. No significant differences in plasma CCK levels, integrated CCK response or gallbladder emptying were found in the patients according to the site of fat application. It is concluded that endogenous CCK secretion and gallbladder emptying in response to intragastric fat are significantly delayed in healthy subjects but not in patients with partial gastrectomy, in whom gastric emptying is accelerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of pancreatic enzymes on release of cholecystokinin-pancreozymin in response to fat.

In dogs prepared with either pancreatic duct ligation (PDL) or chronic pancreatic fistula (PF), we investigated the effect of pancreatic enzymes on release of cholecystokinin (CCK) in response to corn oil in the upper small intestine. In control dogs without PDL, intraduodenal administration of corn oil (Lipomul containing 15 mmol of triglyceride) resulted in a marked and sharp increase in plasma CCK concentration during the 1st h, which then decreased during the following 1.5 h. In PDL dogs, on the other hand, no immediate increase occurred during the 1st 45 min after which a modest but gradual increase occurred in plasma CCK concentration during the following 2 h. Likewise, plasma CCK concentration increased significantly when Lipomul predigested with pancreatic enzymes or oleic acid was administered to PDL dogs. The increase was comparable to the response to Lipomul alone in control dogs. The infusion of Lipomul resulted in similar responses of plasma CCK in PF dogs as were found in PDL dogs when pancreatic juice was diverted to the exterior from the duodenum. The increases in plasma CCK paralleled the pancreatic protein secretion, and a significant correlation was found between plasma CCK concentration and the protein output. The present observations indicate that release of endogenous CCK by fat from the upper small intestine depends on an adequate digestion of neutral fat by pancreatic enzymes. Thus pancreatic enzymes play an important role on release of CCK in response to a neutral fat.

Effects of nutritional status and acute variation in substrate supply on cardiac and skeletal-muscle fructose 2,6-bisphosphate concentrations

We examined the long-term effects of nutritional status and the acute effects of changes in exogenous carbohydrate- and lipid-substrate supply and utilization on fructose 2,6-bisphosphate (Fru-2,6-P2) concentrations in heart, gastrocnemius and soleus. Starvation decreased Fru-2,6-P2 concentrations in all three muscles. The acute administration of insulin and glucose increased skeletal-muscle Fru-2,6-P2 in the fed, but not in the starved, state, but cardiac Fru-2,6-P2 was unchanged. Cardiac and skeletal-muscle Fru-2,6-P2 concentrations were unaffected by acute increases in fatty acid supply produced by the administration of corn oil plus heparin, or by acute decreases in fatty acid supply produced by inhibition of lipolysis. Differences in cardiac and skeletal-muscle Fru-2,6-P2 concentrations observed in response to starvation were not reversed by administration of glucose or glucose plus insulin, or by inhibition of lipolysis, even though changes in citrate (heart), acylcarnitine (heart) and glycogen (skeletal muscle) were observed. Concentrations remained low for at least 8 h after chow re-feeding, but the fed value was restored by 24 h.

Enhancement of the Hepatotoxicity of Chloroform in B6C3F1 Mice by Corn Oil: Implications for Chloroform Carcinogenesis

A recent study of the ability of chloroform in drinking water to produce cancer reported that male Osborne-Mendel rats developed renal tumors, but that female B6C3F1 mice failed to develop hepatocellular carcinomas. The results obtained in the male Osborne-Mendel rats were comparable to those observed in an earlier study sponsored by the National Cancer Institute (NCI). On the other hand, the lack of an increased incidence of hepatocellular carcinomas in female B6C3F1 mice was in sharp contrast to previously reported results. The doses of chloroform used were comparable to that which produced an 85% incidence in the NCI study. We have investigated the extent to which the vehicle might be responsible for the different results in these two studies by examining the differential effects of chloroform when it was administered by gavage using corn oil versus a 2% Emulphor suspension as the vehicle. Male and female B6C3F1 mice were administered chloroform at 60, 130, and 270 mg/kg per day for 90 days. At sacrifice, body and organ weights were measured, and blood was recovered to perform the following serum chemistry measurements (in order of priority): glutamate oxalacetate transaminase (SGOT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and triglyceride (TG) levels. The liver was sectioned for histopathological examination. Chloroform increased SGOT levels significantly only when administered in corn oil at a dose of 270 mg/kg in both male and female mice. It had no effect on LDH activity. There was a small increase in BUN when chloroform was administered in corn oil, but not when administered in 2% Emulphor. When administered in corn oil, chloroform significantly decreased serum TG levels but was without effect on this parameter when administered in 2% Emulphor. Chloroform decreased body weight and increased liver weight with both vehicles, but the effects were significantly greater when it was administered in corn oil. Mice administered chloroform in corn oil displayed a significant degree of diffuse parenchymal degeneration (5 of 10 males and 1 of 10 females) and mild to moderate early cirrhosis (5 of 10 males and 9 of 10 females); significant pathological lesions were not observed in the animals administered corn oil without chloroform nor in mice receiving chloroform in 2% Emulphor. These data indicate that administration of chloroform by corn oil gavage results in more marked hepatotoxic effects than observed when it is provided in an aqueous suspension.(ABSTRACT TRUNCATED AT 400 WORDS)