Effect of polychlorinated biphenyls on lipids and ascorbic acid metabolism in streptozotocin-induced diabetic rats

Metabolic changes in lipids, ascorbic acid, and hepatic microsomal cytochrome P-450 by feeding polychlorinated biphenyls (PCB) were investigated in streptozotocin-induced diabetic rats. Streptozotocin (STZ, 60 mg/kg body weight) was injected in Wistar male rats intraperitoneally. Diabetic and non-diabetic rats were fed ad libitum a 20% casein-based control diet or a PCB-containing diet (200 mg/kg diet) for 9 days. Body weight decreased significantly in STZ-induced diabetic rats with or without PCB (groups PD and D, respectively). In rats of group D, urinary ascorbic acid excretion was 15 times higher than that in non-diabetic rats fed a control diet (group C). Dietary PCB caused 30-fold higher urinary ascorbic acid excretion in non-diabetic rats (group P) than that in group C. In group PD, urinary ascorbic acid was nearly 60 times higher than that in group C. Ascorbic acid in liver and kidney was significantly lower in group D than in group C, and it was significantly lower in group PD than in group P. Liver microsomal cytochrome P-450 and b5 were both increased by dietary PCB in group P. Addition increase in these enzymes was observed in diabetic rats by PCB. Serum total cholesterol was 1.8 times higher in group P than in group C. Further increase in serum total cholesterol was observed in group PD. These data suggest that metabolic changes in lipids and ascorbic acid induced by the dietary xenobiotic were magnified in STZ-induced diabetic rats.     

Effect of dietary ascorbic acid, cholesterol and PCB on cholesterol and bile acid metabolism in a rat mutant unable to synthesize ascorbic acid

The effect of acute or chronic ascorbic acid deficiency on the activity of hepatic cholesterol 7 alpha-hydroxylase and fecal excretion of bile acids was investigated in ODS-od/od (OD) rats (a rat mutant unable to synthesize ascorbic acid) fed a purified basal diet or purified diets containing either cholesterol (2%) or polychlorinated biphenyl (PCB) (200 mg/kg). In OD rats, the dietary requirement of ascorbic acid to maintain normal growth and normal levels of cholesterol in serum and liver is about 300 mg of ascorbic acid/kg diet. In OD rats fed the basal diet, acute or chronic ascorbic acid deficiency did not affect the activity of hepatic cholesterol 7 alpha-hydroxylase and fecal excretion of bile acids. However, in OD rats fed diets containing either cholesterol or PCB, acute ascorbic acid deficiency caused a higher level of serum cholesterol, a lower activity of hepatic cholesterol 7 alpha-hydroxylase and a lower excretion of fecal bile acids than in OD rats fed a basal diet containing an adequate level of ascrobic acid. It is concluded that acute ascorbic acid deficiency causes a hypercholesterolemia due to the depression of bile acid synthesis in OD rats fed a purified diet with cholesterol or PCB.     

Hepatic cysteine dioxygenase activity and sulfur amino acid metabolism in rats: possible indicators in the evaluation of protein quality

Experiments were carried out to examine the possibility that the sulfur amino acid metabolism of rats may be an indicator of the nutritional value of dietary protein. Rats were fed diets containing 8, 16 or 24% of gluten, soy protein or casein for 3 wk. Hepatic cysteine dioxygenase activity, hepatic concentration of glutathione, cysteine and taurine and urinary taurine were examined. In addition, the sulfur amino acid metabolism of rats fed these diets fortified with the appropriate first limiting amino acid for 7 d was also examined. High urinary taurine excretion was observed in the three gluten groups, whereas very low urinary taurine excretion was observed with up to 24% soy protein or up to 16% casein. The hepatic hepatic cysteine dioxygenase activities of the gluten diet groups were higher than those of corresponding soy protein or casein diet groups, except that of rats fed the 24% casein diet. The hepatic concentrations of both glutathione and cysteine in gluten diet groups were also higher than those of corresponding soy protein or casein diet groups, except 24% soy protein and 16 and 24% casein diet groups. In rats fed the casein or soy protein diets urinary taurine excretion and hepatic cysteine dioxygenase activity increased with increasing methionine supplementation, the first limiting amino acid. Conversely, in rats fed the gluten diet both urinary taurine excretion and hepatic cysteine dioxygenase activity decreased with increasing lysine supplementation, the first limiting amino acid. These findings suggest that urinary taurine excretion and hepatic cysteine dioxygenase activity may be useful as sensitive indicators of the nutritional value of dietary protein.     

Effect of dietary ascorbic acid and vitamin E on metabolic changes in rats and guinea pigs exposed to PCB

The effect of the addition of dietary ascorbic acid and/or vitamin E (all-rac-alpha-tocopheryl acetate) in rats and guinea pigs exposed to PCB (polychlorinated biphenyls) was studied. Rats were fed diets containing one of three levels of vitamin E (30, 500 or 1000 mg/kg diet) with or without PCB (200 mg/kg diet). Guinea pigs were fed diets containing PCB (40 mg/kg diet) with 200 or 1000 mg ascorbic acid/kg diet and/or 70 or 2000 mg vitamin E/kg diet. For rats fed PCB, ascorbic acid in urine was 40-fold higher and in liver, 2-fold higher than for rats fed no PCB, and thiobarbituric acid-reactive substances (TBA-RS, indicators of lipid peroxidation) in liver was 1.5-fold higher. In rats fed PCB, high dietary vitamin E significantly lowered the urinary ascorbic acid and TBA-RS. Liver ascorbic acid was lowered by high dietary vitamin E only in control rats. In guinea pigs, feeding PCB caused severe growth retardation and the liver TBA-RS was 1.8-fold higher than in guinea pigs not fed PCB. Feeding high levels of both ascorbic acid and vitamin E was more effective in reversing the growth depression and in lowering TBA-RS level (due to PCB) than feeding the vitamins separately. Ascorbic acid metabolism in rats was affected by high dietary vitamin E. The possibility of a higher requirement for ascorbic acid and vitamin E in guinea pigs exposed to PCB was indicated. Interaction of ascorbic acid and vitamin E in animals exposed to PCB was suggested.     

Characteristic properties of isolated soy protein in the metabolic changes due to dietary polychlorinated biphenyls

Feeding polychlorinated biphenyls (PCB) to rats causes an increase in activity of liver microsomal drug-metabolizing enzyme system, plasma level of cholesterol and urinary ascorbic acid. The influences of different types of dietary protein, including whole-egg protein, isolated soy protein and wheat gluten, on these metabolic responses were studied. In the animals not receiving PCB, the activity of drug-metabolizing enzymes and plasma cholesterol were well correlated with the quality of dietary protein as shown by growth rate and nitrogen balance. In the animals fed 200 ppm of PCB containing diets, aniline hydroxylase activity still correlated with the protein quality, but in the animals fed isolated soy protein diets containing PCB, aminopyrine N-demethylase activity, cytochrome P-450 content, plasma cholesterol and urinary ascorbic acid were less than those expected from the biological value. However, supplementation of methionine to isolated soy protein diet containing PCB caused a marked increase in urinary ascorbic acid and plasma cholesterol. This suggests that more sulfurcontaining amino acids are required for the maximum increase in these metabolic parameters than those for the growth rate and nitrogen balance.     

Long-term effects of dietary polychlorinated biphenyl and high level of vitamin E on ascorbic acid and lipid metabolism in rats

Long-term feeding of purified diets containing (per kg diet) 100 mg of polychlorinated biphenyl (PCB) and 1000 mg of vitamin E (RRR-alpha-tocopheryl acetate) to male Wistar rats was carried out. Rats fed a diet containing PCB rapidly became hypercholesterolemic and maintained high cholesterol levels throughout the 240 d of the experiment. Rats fed a high dietary level of vitamin E plus PCB had higher serum cholesterol and lower liver cholesterol than rats fed a lower level of vitamin E plus PCB. In rats fed PCB, urinary excretion of ascorbic acid was higher than in rats not fed PCB. Urinary ascorbic acid was lower in rats fed high levels of vitamin E plus PCB than in those fed the normal levels of vitamin E plus PCB. Rats fed PCB had lower liver vitamin A storage and higher vitamin A in kidney than rats not fed PCB. This implies that a redistribution of vitamin A occurred in rats fed PCB. Histological observations revealed that central halves of the hepatic lobules of rats fed PCB showed distinct changes consisting of hypertrophy of hepatocytes in the perivenous region and accumulation of vacuoles (lipid droplets) in the cells in the remaining affected portion. Administration of a high dose of vitamin E could not ameliorate this lesion while the treatment depressed effectively the lipid peroxidation. This suggests that the lipid peroxidation was not responsible for the hepatic damage induced by PCB.     

Bile acid conjugation and hepatic taurine concentration in rats fed on pectin

A relationship between bile acid conjugation and hepatic taurine concentration was investigated in rats fed on citrus pectin. When rats were fed on the diets containing varying amounts of pectin (10, 30, 60 and 100 g/kg dietary levels), biliary excretion of bile acids increased as the dietary levels of pectin increased. The increase was entirely due to the glycine-conjugated bile acids. The biliary excretion of taurine-conjugated bile acid was somewhat decreased as the dietary level of the fibre increased. Consequently, most of the bile acids were conjugated with glycine in rats fed on the diet containing 100 g pectin/kg. On the other hand, dietary cellulose (60 and 100 g/kg) did not affect the biliary bile acid excretions. The major proportion of bile acids in rats receiving a fibre-free diet and the diets containing cellulose were conjugated with taurine. Hepatic taurine concentrations decreased as the dietary levels of pectin, but not of cellulose, increased. Although dietary pectin (100 g/kg) also slightly decreased the taurine concentration in the kidney, those concentrations in other non-hepatic tissues examined (heart, brain and serum) were unaffected by the dietary fibre. Supplementation of the diet containing 100 g pectin/kg with methionine (10 g/kg) and taurine (10 and 50 g/kg) strikingly increased hepatic taurine concentrations. In this situation, the conjugation of bile acid with glycine was almost abolished and taurine conjugates became abundant in the bile of these animals. It is suggested that dietary pectin mediated an increase in the biliary bile acid excretion which may have depleted the hepatic pool of taurine available for bile acid conjugation and, thus, increased glycine conjugation of bile acids.     

Requirement for ascorbic acid in a rat mutant unable to synthesize ascorbic acid

The activities of several enzymes involved in hepatic ascorbic acid synthesis and the requirement of dietary ascorbic acid were investigated in the OD (osteogenic disorder) rat, which has a hereditary defect in ascorbic acid-synthesizing ability. No activity of hepatic L-gulonolactone oxidase was detected in OD rats. However, OD rats maintained the normal activities of hepatic UDPglucose dehydrogenase, UDPglucuronyl transferase and beta-glucuronidase. Hemorrhage in muscle and leg joints, lower hepatic content of cytochrome P-450 and lower activities of hepatic drug-metabolizing enzymes, higher serum and adrenal levels of corticosterone and lower urinary excretion of hydroxyproline were observed in ascorbic acid-deficient OD rats than in OD rats fed 300 mg ascorbic acid/kilogram diet. Consequently, we conclude that OD rats cannot synthesize ascorbic acid because of the lack of activity of hepatic L-gulonolactone oxidase and that the dietary addition of about 300 mg ascorbic acid (per kilogram diet) is enough to prevent signs of vitamin C deficiency and to achieve maximum growth, and that more than 300 mg ascorbic acid per kilogram diet may be required for the maximum activity of hepatic drug-metabolizing enzymes.     

Effects of some xenobiotics on ascorbic acid metabolism in rats

The administration of xenobiotics, PCB, DDT, or aminopyrine to rats causes a marked increase in urinary excretion of ascorbic acid and in various tissue levels of ascorbic acid. When rats were fed diet containing 200 ppm PCB or 500 ppm DDT (14 days), the incorporations from D-(U-14C) glucose into ascorbic acid in liver were significantly increased. The dietary addition of 200 ppm PCB, 500 ppm DDT, 2,000 ppm pentobarbital or 3,000 ppm chloretone caused a significant increase in the activity of hepatic UDPglucose dehydrogenase, but did not affect the activity of hepatic L-gulonolactone oxidase. Good correlation between the liver level of ascorbic acid and the activity of hepatic UDPglucose dehydrogenase was observed. Subsequently, in rats fed the basal diet (30% casein diet) or the diet containing 200 ppm PCB, the specific activities of ascorbic acid in urine and in various tissues were measured 6 hours, 12 hours and 24 hours after the oral administration of L-(l-14C)ascorbic acid. Dietary PCB accelerated the disappearances of radioactivities in ascorbic acid in urine and various tissues, that is, shortened the half lives of radioactivities in ascorbic acid. It is likely that the administration of xenobiotics, such as PCB or DDT, to rats increases the biosynthesis of ascorbic acid and accelerates concomitantly the turnover of ascorbic acid in body.     

Dietary sesame seed and its lignan increase both ascorbic acid concentration in some tissues and urinary excretion by stimulating biosynthesis in rats

We previously showed that the intake of sesamin, a major lignan in sesame seed, decreased lipid peroxidation and elevated tocopherol concentration in rat tissues. In this study, we examined the effect of dietary sesame seed and sesamin on the ascorbic acid concentration in rat tissues. Rats (4-wk-old) were fed either a vitamin E-free diet, or a diet containing 50 mg gamma-tocopherol/kg, one containing 2 g sesamin/kg, one containing 50 mg gamma-tocopherol/kg and 2 g sesamin/kg, or one containing 200 g sesame seed/kg for 28 d. The dietary sesamin and sesame seed elevated ascorbic acid concentrations in the liver and kidney, and increased urinary excretion in those Wistar rats. The dietary sesamin also elevated the hepatic mRNA levels of cytochrome P450 (CYP) 2B, and UDP-glucuronosyltransferase (UGT) 1A and 2B. In contrast, neither the sesamin nor the sesame seed affected the liver concentration of ascorbic acid in ODS rats with a hereditary defect in ascorbic acid synthesis, though the dietary sesame seed elevated the UGT1A and 2B mRNA levels in the liver. In addition, the sesame seed elevated the gamma-tocopherol concentration in the various ODS rat tissues and the ascorbic acid concentrations in the kidney, heart and lung, while reducing the thiobarbituric acid reactive substance concentration in the heart and kidney. These results suggest that dietary sesame seed and its lignan stimulate ascorbic acid synthesis as a result of the induction of UGT1A and the 2B-mediated metabolism of sesame lignan in rats. The data of ODS rat studies also suggest that dietary sesame seed enhances antioxidative activity in the tissues by elevating the levels of two antioxidative vitamins, vitamin C and E.     

The effect of dietary protein on nitrogen and sulfur metabolism in portacaval-shunted rats

The effect of varying the amount of protein in the diet on postoperative recovery, plasma ammonia, urinary orotic acid and metabolism of sulfur-containing amino acids was examined in rats with portacaval shunts (PCS). Food intake and weight gain were lower in both PCS and control rats fed a low (6%) casein diet unsupplemented with methionine compared with rats fed an adequate (18%) casein diet. PCS rats fed 60% casein ate slightly less and took longer to recover their preoperative body weight compared to 60% controls. Shunted rats were consistently hyperammonemic and orotic aciduric compared to controls. Increasing protein in the diet elevated plasma ammonia and urinary orotic acid in all rats to levels above those of the rats fed 18% casein, but the effect was greater in rats with PCS. After i.p. injection of L-[35S]methionine or L-[35S]cysteine, urinary 35S and [35S]sulfate excretion increased and [35S]taurine and total taurine excretion decreased in all rats fed 60% casein. These changes are consistent with our observation that hepatic activities of cysteine dioxygenase and cysteine sulfinate:alpha-ketoglutarate aminotransferase increased and that of cysteine sulfinate decarboxylase decreased in rats fed the high protein diet. The effect of dietary treatment on both urinary taurine excretion and decarboxylase activity was greater in PCS rats than in controls. Although PCS rats fed a high protein diet may have a decreased taurine-synthesizing capability compared to controls, their ability to oxidize a methionine or cysteine load to sulfate is not compromised by feeding either an 18 or 60% casein diet.     

13-cis-retinoic acid alters methionine metabolism in rats

The effect of dietary 13-cis-retinoic acid (CRA) on hepatic methionine metabolism was examined in young male rats. Rats were fed a 10% casein diet (controls) or this diet supplemented with L-methionine (10 g/kg diet), with or without the addition of CRA (100 mg/kg diet), for 10 d. Methionine-supplemented rats exhibited 7.3- and 1.7-fold greater concentrations of hepatic S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), respectively, relative to controls, which resulted in a 4.9-fold greater SAM:SAH ratio. Likewise, hepatic methionine and taurine concentrations were 6.9- and 4.3-fold greater, respectively, in methionine-supplemented rats than in controls. The addition of CRA to the methionine-supplemented diet prevented the elevations in the hepatic methionine concentration and the SAM:SAH ratio, whereas taurine levels were greater than in methionine-supplemented rats. In rats pretreated with the methionine-supplemented diet, a reduction in the SAM:SAH ratio occurred within 2 d following the addition of CRA to the methionine-supplemented diet. Rats receiving the methionine-supplemented diet exhibited 9.2- and 3.7-fold greater urinary taurine and inorganic sulfate excretions, respectively, relative to controls. Addition of CRA to the methionine-supplemented diet significantly reduced sulfate excretion by 21%. These findings indicate that dietary CRA has the ability to alter the catabolism of methionine and subsequently influence hepatic transmethylation as reflected by the SAM:SAH ratio.     

Effect of dietary soy isoflavone aglycones on the urinary 16alpha-to-2-hydroxyestrone ratio in C3H/HeJ mice

Estradiol is metabolized through two mutually exclusive pathways. 2-Hydroxyestrone (2-OHE,) is antiestrogenic, while 16alpha-hydroxyestrone (16alpha-OHE1) is a potent estrogen. It is suggested that a high urinary 16alpha-OHE1-to-2-OHE1 rato is a biomarker of increased mammary tumor risk. Mice were fed one of the test diets for 21 days. Indole-3-carbinol (2,500 mg/kg diet) increased the cytochrome P-450 content of hepatic microsomes and liver weight and reduced the urinary 16alpha-OHE1-to-2-OHE1 ratio in comparison with the respective value in the control mice. Fermented soy extract (100, 200, or 400 mg isoflavonoid/kg diet), genistein (200 mg/kg diet), and daidzein (200 mg/kg diet) each reduced the urinary 16alpha-OHE1-to-2-OHE1 ratio without increasing the cytochrome P-450 content of hepatic microsomes or liver weight. The combination of genistein and daidzein (100 mg and 100 mg/kg diet) did not have a synergistic effect on the reduction in urinary 16alpha-OHE1-to-2-OHE1 ratio. These data suggest that the soy isoflavonoid aglycones genistein and daidzein and indole-3-carbinol each exert a cancer-preventive effect by shifting metabolism away from the production of genotoxic metabolites toward the production of inactive metabolites.     

Hepatic cysteine sulfinic acid decarboxylase activity in rats fed various levels of dietary casein

A series of experiments was conducted to examine the effects of dietary protein intake on hepatic cysteine sulfinic acid decarboxylase (EC 4.1.1.29) activity and urinary taurine excretion. When rats were fed diets containing 18, 30, 45 or 60% casein for 1 wk, hepatic cysteine sulfinic acid decarboxylase activity (CSAD) decreased in a progressive and significant manner. Enzyme activity in rats fed a 60% casein diet was 25% of the activity measured in rats fed 18% casein. The time course of the change in CSAD activity was examined in rats fed a 60% casein diet. Within 24 h of switching rats from a moderate (18% casein) to high (60% casein) protein diet, enzyme activity decreased by 50% and continued to decline in rats fed the high protein diet for 7 d. The observed decrease in enzyme activity was reversed when rats were refed the 18% casein diet. The half-life of CSAD was calculated to be 2 and 7 d during the diet switch from 18 to 60% casein and from 60 to 18% casein, respectively. The change in enzyme activity was evident after a single high protein meal. In contrast to CSAD activity, urinary taurine excretion increased 140-fold within 2 d of switching rats from an 18 to 60% casein diet. Upon refeeding of the 18% casein diet taurine excretion rapidly decreased. These findings indicate that CSAD responds in a rapid and reversible manner to dietary protein.     

Hepatic microsomal enzyme induction in rats fed varietal cauliflower leaves.

Leaves from a standard, insect-susceptible cauliflower variety and an insect-resistant strain were formulated at either 10 or 25% into semipurified diets for male and female weanling rats. After 3 weeks, relative liver weights, microsomal protein, cytochrome P-450, and activities of hepatic microsomal aminopyrine N-demethylase, aniline hydroxylase, p-nitroanisole O-demethylase, and N-methylaniline N-demethylase were determined. Growth, feed intake, and feed efficiency of male rats were not affected by the inclusion of the dried cauliflower leaf in the diet. However, female rats exhibited a depressed feed intake and increased feed efficiency with cauliflower leaf supplemental diets. Relative liver weights increased with increasing percentage of cauliflower leaves in the diet. Hepatic microsomal enzyme response to cauliflower leaf supplementation of the diet was greater in males than in females. Only aniline hydroxylase activity remained unchanged by the test diets. Male rats showed significant increases in N- and O-demethylation with both the 10 and 25% cauliflower diets, and increased values for microsomal protein and cytochrome P-450 at the 25% supplemental level. Female rats did not show significant hepatic microsomal induction from cauliflower leaf consumption at the 10% level. However, cytochrome P-450 and the metabolism of aminopyrine and p-nitroanisole were enhanced by consumption of cauliflower leaves at 25% of their diet. None of the parameters tested in this study evidenced a difference between the two cauliflower cultivars fed to either sex.     

Effects of retinoic acid on hepatic cytochrome P-450 dependent enzymes in rats under different vitamin A status

The temporal effects of retinoic acid supplementation on hepatic cytochrome P-450-dependent enzymes were studied on the rat. Four groups of male weanling rats were fed semi synthetic diets: two groups containing 0 or 4.4 mg retinol equivalents per kg diet as retinyl palmitate (A- RA- and A+ RA- groups) and two similar groups supplemented with all trans retinoic acid (12 mg/kg diet) (A- RA+ and A+ RA+ groups). After five or ten weeks of feeding, the rats were killed, liver microsomes were prepared and assayed for aniline hydroxylase, aminopyrine N demethylase activities and cytochrome P-450 levels. Whereas no change was observed between the four groups after 5 weeks, the following modifications appeared after 10 weeks: Vitamin A deficiency decreased hepatic drug metabolism by phase I enzymes (hydroxylase and N demethylase) but only when liver storage pool was not detectable. Vitamin A concentration as low as 4 micrograms/g is sufficient to avoid any perturbation of these enzymes. Parallel to a sparing effect on liver reserves of vitamin A, retinoic acid maintained a normal activity of enzymes of xenobiotic metabolism. However, retinoic acid treatment produced an alteration of phase I enzymes in vitamin A supplemented group (A+ RA+). As this was accompanied by a doubling of vitamin A liver reserves, compared to A+ RA- group, it is suggested that this might result from a liver vitamin A overloading, leading to membrane damage perturbing microsomal enzymes. These results indicate the need for a more careful use of retinoids as a therapeutic agent.     

Urinary taurine excretion as a function of taurine intake in adult cats.

Experiments were designed to develop a urinary excretion model for the study of taurine status in adult cats. The time course of changes in urinary taurine excretion in response to alterations in dietary taurine was examined in Experiment 1. Urinary taurine excretion decreased rapidly when cats were switched from a casein diet supplemented with 2000 mg crystalline taurine/kg diet to a diet containing no supplemental taurine reaching a plateau in 2 d, but the cats required 7 d to reach a plateau when switched from the nonsupplemented diet to the 2000 mg taurine/kg diet. In Experiment 2, the casein diets contained graded levels of crystalline taurine (0, 250, 500, 1000, 1500 or 2000 mg/kg). After a 7-d adjustment period, urinary taurine excretion was quantified over 5 d, and blood taurine concentrations were measured on d 6. Plasma taurine concentration increased linearly (r = 0.88) as taurine intake increased, but whole-blood taurine increased asymptotically. Taurine intakes of greater than 96 mumol/(kg body wt.d) resulted in urinary excretion rates that were 15 times greater than those occurring below this break point. We suggest that urinary taurine excretion by cats fed taurine at levels above the break point has potential for estimating taurine bioavailability in intact meat-source proteins.     

Long-term effects of inadequate and excessive dietary ascorbate on bile acid metabolism in the guinea pig

The effects of long-term chronic ascorbic acid deficiency and excessive ascorbic acid consumption on bile acid metabolism and biliary lipid composition were studied in guinea pigs. Male, weanling guinea pigs were fed a cereal-based scorbutigenic diet for 19 or 21 weeks. Ascorbic acid was administered either orally at 0.15 (group A) or 2.0 (group B) mg/100 g body weight, or it was mixed in the diet at levels of 500 (group C), 16-22 (group D), or 20,000 mg/kg (group E). Chronic ascorbic acid deficiency (groups A and D) caused depression of hepatic cytochrome P-450 levels and elevation of plasma cholesterol. Excessive ascorbate consumption did not alter these parameters relative to control levels. In contrast to results obtained in guinea pigs fed low or high amounts of ascorbate for 7-9 weeks, prolonged consumption of inadequate or excessive ascorbate resulted in little or no change in bile acid metabolism and biliary lipid composition except that bile acid pool size was increased 12% as a result of excessive ascorbate ingestion. Results of the present study suggest that there may be important differences in the guinea pig's metabolic response to ascorbic acid deficiency and ascorbic acid excess, depending on the length of the experimental period.     

Modulation of UDPglucuronosyltransferase activity in rats by dietary lipids

Male Wistar rats were fed for 40 d a purified diet whose lipid source (60 g/kg diet) was coconut, peanut, corn or fish (herring) oil. A low lipid (lipid-deficient) diet (corn oil, 2 g/kg diet) was also fed to some rats. There were no significant differences in final body weights of rats fed the coconut, peanut, and corn oil diets. Rats fed the fish oil diet gained less weight than those fed any other diet. However, liver weight, ratio of liver to body weight, and protein content were not affected by any of the diets. The plasma cholesterol concentration of rats fed fish oil was lower than that of the other groups of rats. This diet resulted in the highest cytochrome P-450 concentration and markedly enhanced epoxide hydrolase activity. No difference in the level in cytochrome P-450 was noted between the groups of rats fed the vegetable oils. Epoxide hydrolase activity was also significantly higher with the corn oil diet. Interestingly, only glucuronidation of group I substrates was stimulated by the fish or corn oil diets and lowered by the coconut oil diet. Liver microsomes of rats fed fish oil contained a high level of lipid peroxides; this diet greatly stimulated NADPH-dependent peroxidation. The differential stimulation of UDPglucuronosyltransferase activity towards group I substrates could be the results of a toxic action of the fish oil diet as suggested by the concomitant enhancements of epoxide hydrolase, transaminase activities and peroxide content.     

Effects of dietary ethanol on ascorbic acid and lipid metabolism, and liver drug-metabolizing enzymes in rats

Effects of dietary ethanol on ascorbic acid and lipid metabolism, and liver drug-metabolizing enzymes in rats fed a semi-purified diet containing a powdered ethanol preparation (30 cal% in the diet) were studied. Administration of ethanol increased urinary ascorbic acid excretion (p less than 0.001) and ascorbic acid level in the liver (p less than 0.001) and the spleen (p less than 0.01). The activity of hepatic aniline hydroxylase was increased (p less than 0.05) by ethanol feeding but that of aminopyrine N-demethylase was not. Increases of serum total and high-density-lipoprotein (HDL) cholesterol level, commonly observed by the administration of xenobiotics, were not observed. These results showed ethanol possessed rather similar properties to xenobiotics such as polychlorinated biphenyls (PCB) or 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane (DDT) in some metabolic changes. In this study, no accumulation of lipid in the liver was observed.