Urinary Excretion Of Ascorbic Acid Research Articles

Antioxidant, Antistress, Nootropic activity and its Correlation studies of aqueous extract of Punica granatum fruit estimated by Noninvasive biomarkers and Y-maze test in rodents

The memory loss associated with increased oxidative stress due to increased level of free radicals. Oxidative stress has been involved in several diseases includes cancer, atherosclerosis and neurodegenerative diseases.This study aimed to estimate the correlation of antioxidant and antistress activity with nootropic activity of aqueous extract of pomegranate (Punica granatum) by in-vivo noninvasive studies using rats. The in-vitro antioxidant activity was determined based on the ability of the Punica granatum to scavenge free radicals and lipid peroxidation inhibiting activity. The antistress effect of the aqueous extract of Punica granatum for 24h treatment (100 and 300mg/kg, p.o.) was evaluated by using the forced swim stress test in rats. The 24h urinary excretion of vanillylmandellic acid (VMA), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and ascorbic acid (AA) was determined in all groups under normal and stressed conditions by HPLC and spectrophotometric methods in all groups, were selected as noninvasive biomarkers. Nootropic activity activities of Punica granatum fruit extract were estimated as locomotor and working memory in rats in a Y-maze apparatus. Administration of aqueous extract of Punica granatum at a dose of 100 and 300mg/kg reduced the urinary metabolite levels. Punica granatum treatment showed significant dose dependent variation in non-invasive biomarker levels in urine samples of rats taken after 24h. The treatment with Punica granatum extracts improved the percentage entry of rats into safer zone, it means acquisition (learning) retention and retrieval (memory) were improved in rats compared to stress controls. Cognition determined by working memory and locomotor activity results were shown to be dose-dependent. The results of this study strongly suggestedantioxidant, antistress and nootropic activity effect of Punica granatumin rodents were correlated. The data obtained were analyzed by one-way ANOVA followed bytukey test. p<0.05 was considered to be significant. There is substantial evidence that flavonoids play an active role in providing antioxidant, antistress and nootropic activities of Punica granatum extracts. The findings of the present investigations indicate that the Punica granatum has significant antistress activity, which may be due to the immunostimulating property and increased resistance, nonspecifically, against all experimental stress conditions. The study provided scientific evidence for their utility as nootropic agents and to advocate their use in foods.

UDP Glucuronosyltransferase Gene Expression is Involved in the Stimulation of Ascorbic Acid Biosynthesis by Xenobiotics in Rats

Wistar-Shi (genotype +/+), heterozygous Gunn (j/+) and homozygous Gunn (j/j) rats was injected intraperitoneally with 3-methylcholanthrene (3MC) dissolved in corn oil. In rats of all genotypes the hepatic concentration of UDP glucuronosyltransferase (UDPGT) mRNA was increased at 48 and 96 h after the treatment with 3MC. Hepatic activity of 4-nitrophenol UDPGT was increased by 3MC in Wistar-Shi rats and heterozygous Gunn rats but not in homozygous Gunn rats. Urinary ascorbic acid excretion increased 72 and 96 h after the injection with 3MC in Wistar-Shi and heterozygous Gunn rats but not in homozygous Gunn rats. Ninety-six hours after the injection with 3MC, the hepatic concentration of ascorbic acid in Wistar-Shi rats was 90% higher than that in the corresponding control group, whereas in heterozygous and homozygous Gunn rats the increases were 70 and 30%, respectively. Wistar-Shi rats and homozygous Gunn rats were also injected daily for 3 d with sodium phenobarbital. In rats of both genotypes, the activity and hepatic concentration of chloramphenicol-UDPGT mRNA and liver and urine ascorbic acid concentration were increased by sodium phenobarbital. The data indicate that the stimulation of the expression of both the 4-nitrophenol and chloramphenicol UDPGT genes plays a key role in the ascorbic acid biosynthesis induced by 3MC and sodium phenobarbital.

ISOLATION OF TECOMINE FROM ALKALOID FRACTION, INVESTIGATION OF ADAPTOGENIC AND NEUROPSYCHOPHARMACOLOGICAL EFFECTSOF ETHANOLIC, ETHYL ACETATE AND HEXANE FLOWER EXTRACTS OF TECOMA GAUDICHAUDI

The present study aims to evaluate antistress and neuropharmacological parameters of ethanolic, ethyl acetate and hexane flower extracts of Tecoma gaudichaudi. Forced swim stress was used to evaluate antistress activity. The 24 h urinary excretion of vanillylmandelic acid (VMA) and ascorbic acid were determined by spectrophotometric methods in all groups under normal and stressed conditions. In the present study, the extracts (200 and 400 mg/kg, p.o.) were investigated for nootropic activity in rats with and without stress. Cook’s pole climbing apparatus measures conditioned avoidance response, elevated plus maze determines transfer latency and staircase test calculates the number of steps climbed and rearings in normal and stress induced rats to assess cognitive-improving activities. Cognition was enhanced by daily administration of Tecoma gaudichaudi extracts at doses of 200 and 400 mg/kg, p.o. in dose dependent manner in normal rats. Tecomine and its derivatives were isolated from alkaloidal fraction.

Vitamin sufficiency of children visiting preschool educational institutions from different regions (Moscow region, Yekaterinburg)

Introduction. The deficiency of vitamins is a factor that has a negative impact on the growth and development of the child, it leads to a decrease in nonspecific resistance of the organism, a decrease in the adaptive potential, acts as a risk factor for the development of nutritional disorders, aggravates the process and makes it difficult to treat any disease.
 The purpose of the study. Assessment of the vitamin status of children attending pre-school educational institution by means of non-invasive methods for urinary excretion of ascorbic acid and metabolites of B vitamins.
 Materials and methods. 49 children (26 boys and 23 girls) aged 4 to 7 years living in Moscow region, and 51 children (26 boys and 25 girls) 2-7 years old living in Ekaterinburg were examined in 2015-16 years (winter-spring period). Сhildren received the main nutrition in kindergarten. In the evening time on weekdays children additionally received separate foods or ready meals at home, on weekends (2 of 7 days) children ate at home. The supply with vitamins C, B1, B2 and B6 was evaluated by its hour urinary excretion.
 Results. The picture of vitamin status of children from different regions turned out to be almost identical. The lack of vitamin B2 was found in about one third of the children, vitamin B1 and B6 insufficiency took place significantly 2 fold more often (in 61.2-76.5%). Decreased vitamin C excretion took place in 34.7% of children from the Moscow region. Only every fifth child was provided with all studied vitamins. A significant number of children showed multivitamin deficiency. Children who received multivitamin supplements were better supplied with these micronutrients.
 Conclusion. The results indicate the need for correction of multimicronutrient insufficiency in children by including in the diet of fortified food products, the use of baby specialized products enriched with micronutrients, and vitamin-mineral supplements intake.

An Experimental Evaluation of Adaptogenic Potential of Standardized Epipremnum Aureum Leaf Extract.

Background:Stress is a normal part of everyday life but chronic stress can lead to a variety of stress-related illnesses including hypertension, anxiety, and depression. In the present investigation, standardized leaf extract of Epipremnumaureum was evaluated for its anti-stress potential.Materials and Methods:For the evaluation of anti-stress activity, groups of mice (n = 6) were subjected to forced swim stress and anoxic stress tolerance test in mice 1h after daily treatment of E.aureumextract. Diazepam (5 mg/kg) was taken as a reference standard. Urinary vanillylmandelic acid (VMA) and ascorbic acid were selected as noninvasive biomarkers to assess the anti-stress activity and plasma cortisol, blood ascorbic acid, and weight of adrenal were measured. The 24 h urinary excretion of VMA and ascorbic acid were determined by spectrophotometric methods in all groups under normal and stressed conditions. The hematological parameters (neutrophils, lymphocytes, and eosinophils) were also determined.Results:Administration of E.aureumat doses of 400 and 600 mg/kg wasfound to be effective in inhibiting the stress induced urinary biochemical changes in a dose-dependent manner. Treatment with E. aureum extract prevents the rise in blood ascorbic acid and plasma cortisol. Moreover, the extract prevented the increase in weight of adrenal gland also significantly increased the anoxia stress tolerance time. Dose-dependent significant reduction in white blood cell count was observed in anoxic stress tolerance test as compared to stressed group.Conclusion:Hence, the present study provides scientific support for the positiveadaptogenic effect of E. aureum extract.

Nontargeted LC-MS Metabolomics Approach for Metabolic Profiling of Plasma and Urine from Pigs Fed Branched Chain Amino Acids for Maximum Growth Performance.

The metabolic response in plasma and urine of pigs when feeding an optimum level of branched chain amino acids (BCAAs) for best growth performance is unknown. The objective of the current study was to identify the metabolic phenotype associated with the BCAAs intake level that could be linked to the animal growth performance. Three dose-response studies were carried out to collect blood and urine samples from pigs fed increasing levels of Ile, Val, or Leu followed by a nontargeted LC-MS approach to characterize the metabolic profile of biofluids when dietary BCAAs are optimum for animal growth. Results showed that concentrations of plasma hypoxanthine and tyrosine (Tyr) were higher while concentrations of glycocholic acid, tauroursodeoxycholic acid, and taurocholic acid were lower when the dietary Ile was optimum. Plasma 3-methyl-2-oxovaleric acid and creatine were lower when dietary Leu was optimum. The optimum dietary Leu resulted in increased urinary excretion of ascorbic acid and choline and relatively decreased excretion of 2-aminoadipic acid, acetyl-dl-valine, Ile, 2-methylbutyrylglycine, and Tyr. In conclusion, plasma glycocholic acid and taurocholic acid were discriminating metabolites to the optimum dietary Ile. The optimum dietary Leu was associated with reduced plasma creatine and urinary 2-aminoadipic acid and elevated urinary excretion of ascorbic acid and choline. The optimum dietary Val had a less pronounced metabolic response reflected in plasma or urine than other BCAA.

Absorption and Excretion of Ascorbic Acid Alone and in Acerola (Malpighia emarginata) Juice: Comparison in Healthy Japanese Subjects

It has been suggested that some food components, such as bioflavonoids, affect the bioavailability of ascorbic acid in humans. Since little is known in Japan about the effective intake of this dietary requirement, we tested young Japanese males after the ingestion of commercial ascorbic acid or acerola (Malpighia emarginata DC.) juice to compare the quantities absorbed and excreted. Healthy Japanese subjects received a single oral dose of ascorbic acid solution (50, 100, 200 or 500 mg) and received distilled water as a reference at intervals of 14 d or longer. All subjects were collected blood and urine until 6 h after ingestion and evaluated for time-dependent changes in plasma and urinary ascorbic acid levels. Predictably, the area under the curve (AUC) values in plasma and urine after ingestion increased dose-dependently. Next, each subject received diluted acerola juice containing 50 mg ascorbic acid. Likewise, their plasma and urinary ascorbic acid concentrations were measured. In plasma, the AUC value of ascorbic acid after ingestion of acerola juice tended to be higher than that from ascorbic acid alone. In contrast, the urinary excretion of ascorbic acid at 1, 2 and 5 h after ingestion of acerola juice were significantly less than that of ascorbic acid. These results indicate that some component of acerola juice favorably affected the absorption and excretion of ascorbic acid.

Modulation of ascorbic acid metabolism by cytochrome P450 induction revealed by metabonomics and transcriptional profiling

In the present study, NMR-based urinary metabonomic profiles resulting from dosing with widely recognized microsomal enzyme inducers were evaluated in male rats. Wistar or Sprague-Dawley rats were dosed daily by oral gavage with phenobarbital (PB; 100 mg/kg), diallyl sulfide (DAS; 500 mg/kg), the investigational compound DMP-904 (150 mg/kg), or beta-naphthoflavone (BNF; 100 mg/kg) for 4 days, and urine was collected daily for analysis. Compounds known to increase cytochrome P450 2B enzymes, including PB, DAS and DMP-904, increased the urinary excretion of gulonic and ascorbic acid in a time-dependent manner, reaching a maximum following 3-4 days of dosing. In contrast, BNF, an agent that induces primarily Cyp1A enzymes, did not increase gulonic or ascorbic acid excretion, despite inducing Cyp1A1 more than 200-fold. Given the metabonomic results, hepatic transcriptional changes in the regulation of ascorbic acid biosynthesis were determined by RT-PCR. All Cyp2B inducers increased hepatic mRNA levels of aldo-keto reductase 1A1, an enzyme that catalyzes the formation of gulonic acid from glucuronate with concurrent decreased expression of both regucalcin (Rgn), the enzyme responsible for conversion of gulonic acid to gulono-1, 4-lactone and gulonolactone oxidase (Gulo), the rate-limiting enzyme in ascorbate biosynthesis. These effects would be expected to increase levels of gulonic acid. In addition, Cyp2B inducers also increased hepatic expression of enzymes regulating ascorbic acid reutilization including glutaredoxin reductase (Glrx2) and thioredoxin reductase (Txnrd1). In contrast, BNF did not effect hepatic expression of any enzyme regulating gulonic or ascorbic acid biosynthesis. Thus, some microsomal enzyme inducers alter transcriptional regulation of ascorbic acid biosynthesis, and these changes are detected by noninvasive metabonomic profiling. However, not all microsomal enzyme inducers appear to alter ascorbic acid metabolism. Finally, the work illustrates how metabonomic results can direct additional studies to determine the biochemical mechanisms underlying changes in urinary metabolite excretion.

Adaptogenic and nootropic activities of aqueous extract of Carum carvi Linn. (Caraway) fruit: An experimental study in Wistar rats

In the present investigation the aqueous extract of Carum carvi was evaluated for antistress activity in normal and stress induced rats. The extract was studied for nootropic activity in rats and in vitro antioxidant potential to correlate its antistress activity. For the evaluation of antistress activity groups of rats were subjected to forced swim stress one hour after daily treatment of Carum carvi extract. Urinary vanillylmandelic acid (VMA) and ascorbic acid were selected as non invasive biomarkers to assess the antistress activity. The 24 h urinary excretion of vanillylmandelic acid (VMA) and ascorbic acid was determined in all groups under normal and stressed conditions. The nootropic activity of the extract as determined from acquisition, retention and retrieval in rats was studied by conditioned avoidance response using Cook’s pole climbing apparatus. The in vitro antioxidant activity was determined based on the ability of Carum carvi to inhibit lipid peroxidation in liver and brain homogenates. Daily administration of Carum carvi at doses of 100, 200 and 300 mg/kg body weight one hour prior to induction of stress inhibited the stress induced urinary biochemical changes in a dose dependent manner. However no change in the urinary excretion of VMA and ascorbic acid was observed in normal animals at all the doses studied. The cognition, as determined by the acquisition, retention and recovery in rats was observed to be dose dependent. The extract produced significant inhibition of lipid peroxide formation in comparison with ascorbic acid in a dose dependent manner in both liver and brain. The present study provides scientific support for the antistress (adaptogenic), antioxidant and nootropic activities of Carum carvi extract and substantiates its traditional use as a culinary spice in foods as beneficial and scientific in combating stress induced disorders.

Oxalic Acid as a Uremic Toxin

Oxalic acid (OA) is thought to be a uremic toxin that participates in the pathogenesis of uremic syndrome. The objectives of this study were to: (1) evaluate the plasma levels of OA in patients with chronic renal disease with various levels of glomerular filtration rate and after renal transplantation; (2) investigate the salivary secretion of OA and ascorbic acid in healthy subjects and in patients with chronic renal failure (CRF); (3) examine the influence of water and sodium diuresis and furosemide administration on the urinary excretion of OA and ascorbic acid in healthy subjects and in CRF patients without dialysis treatment; and (4) evaluate the influence of renal replacement therapy (RRT) on secondary hyperoxalemia in hemodialysis patients. This study was conducted at the Nephrological Department of P.J. Safárik University. Sixty-one patients with chronic renal disease, 64 CRF patients, 32 continuous ambulatory peritoneal dialysis (CAPD) patients, 15 hemodialysis patients, 21 patients after renal transplantation, and 15 healthy subjects were examined. Maximal water diuresis, diets with low (2 g/day) and high (15 g/day) sodium intake, administration of intravenous furosemide (20 mg), and renal replacement therapy (CAPD, hemodialysis, hemofiltration, and postdilution hemodiafiltration) were utilized in the study. In patients with chronic renal disease and those after renal transplantation, direct relationships between plasma OA and serum creatinine were found (r = 0.904 and 0.9431, respectively, P < .01). Despite a high level of plasma OA in uremic patients (23.1 +/- 10 micromol/L), there was no significant difference in salivary OA between control subjects (128 +/- 19 micromol/L) and CRF patients (135 +/- 24 micromol/L). The urinary excretion of OA during maximal water diuresis (from 37.5 to 110.3 micromol/4 hours) and after intravenous furosemide (from 34.5 to 66.7 micromol/3 hours) increased significantly, but was not affected by high intake of NaCl. The most significant decrease of plasma OA was observed during postdilution hemodiafiltration (63.3%). Our study indicates that renal replacement therapy is not effective for a permanent reduction of elevated plasma levels of OA.

Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model

BackgroundThe aerial parts of Vitis vinifera (common grape or European grape) have been widely used in Ayurveda to treat a variety of common and stress related disorders. In the present investigation, the seed extract of V. vinifera was evaluated for antistress activity in normal and stress induced rats. Furthermore, the extract was studied for nootropic activity in rats and in-vitro antioxidant potential to correlate its antistress activity.MethodsFor the evaluation of antistress activity, groups of rats (n = 6) were subjected to forced swim stress one hour after daily treatment of V. vinifera extract. Urinary vanillylmandelic acid (VMA) and ascorbic acid were selected as non-invasive biomarkers to assess the antistress activity. The 24 h urinary excretion of vanillylmandelic acid (VMA) and ascorbic acid were determined by spectrophotometric methods in all groups under normal and stressed conditions. The nootropic activity of the extract as determined from acquisition, retention and retrieval in rats was studied by conditioned avoidance response using Cook's pole climbing apparatus. The in vitro antioxidant activity was determined based on the ability of V. vinifera to scavenge hydroxyl radicals.ResultsDaily administration of V. vinifera at doses of 100, 200 and 300 mg/kg body weight one hour prior to induction of stress inhibited the stress induced urinary biochemical changes in a dose dependent manner. However, no change in the urinary excretion of VMA and ascorbic acid was observed in normal animals at all the doses studied. The cognition, as determined by the acquisition, retention and recovery in rats was observed to be dose dependent. The extract also produced significant inhibition of hydroxyl radicals in comparison to ascorbic acid in a dose dependent manner.ConclusionThe present study provides scientific support for the antistress (adaptogenic), antioxidant and nootropic activities of V. vinifera seed extract and substantiate the traditional claims for the usage of grape fruits and seeds in stress induced disorders.

Characteristics of Ascorbic Acid Metabolism in Scurvy-Prone Spontaneously Hypertensive Rat, SHR-od

SHR-od is a novel strain of rat that spontaneously develops hypertension and has a defect of ascorbic acid (AsA) biosynthesis. The osteogenic disorder Shionogi (ODS) rat is normotensive and also unable to synthesize AsA. To investigate whether or not genetic hypertension affects AsA metabolism, we compared the AsA metabolisms of SHR-od and ODS rats. In this study, a physiological dose of AsA equivalent to the AsA requirement in ODS rats was administered to rats intraperitoneally (i.p. group) or orally (oral group). We measured AsA concentrations in the serum, liver, kidney, adrenal glands, and spleen, and the amount of AsA excreted into the urine. At 25 wk of age (hypertensive status), the AsA concentrations of all tissues tested were significantly lower in SHR-od than in ODS rats in both the i.p. and oral groups. In the i.p. group, the amount of urinary AsA in SHR-od was also lower than that in ODS rats. At 4 wk of age (before the onset of hypertension), liver and spleen AsA concentrations in SHR-od were lower than those in ODS rats in both the i.p. and oral groups. Urinary AsA excretion from SHR-od was not different between the two groups. Our data suggest that the requirement for AsA in SHR-od is increased to maintain tissue AsA concentrations equivalent to those in ODS rats, and that a larger part of the AsA administered to rats in this study is degraded in SHR-od as compared to ODS rats.

Impaired ascorbic acid metabolism in streptozotocin-induced diabetic rats.

Ascorbic acid (AA) metabolism in streptozotocin (STZ)-induced diabetic rats was determined by examining urinary excretion, renal reabsorption, reductive regeneration, and biosynthesis of AA at 3 and 14 days after STZ administration. AA concentrations in the plasma, liver, and kidney of the diabetic rats were significantly lower than those of controls on d 3, and decreased further as the diabetic state continued. Hepatic AA regeneration significantly decreased in the diabetic rats on d 3 in spite of increased gene expressions of AA regenerating enzymes and was further reduced on d 14. Hepatic activity of L-gulono-gamma-lactone oxidase, a terminal enzyme of hepatic AA biosynthesis, also decreased significantly on d 3 and decreased further on d 14. Urinary excretion of AA was significantly increased on d 3, with an increase in urine volume but no change in gene expressions of renal AA transporters (SVCT1 and SVCT2). Urinary excretion of AA was normalized on d 14. The results suggest that impaired hepatic and renal regeneration, as well as increased urinary excretion and impaired hepatic biosynthesis of AA, contributed to the decrease in AA in plasma and tissues of STZ-induced diabetic rats.

In vivo antioxidative capacity of a composite berry juice

In order to test the health protective potential of a special antioxidant-rich juice (containing 30% white grape-, 25% blackcurrant-, 15% elderberry-, 10% sour cherry-, 10% blackberry- and 10% aronia-juice), the bioavailability of its most important bioactive compounds (anthocyanins and ascorbic acid) and the influence of juice consumption on plasma antioxidant capacity and plasma malondialdehyde (MDA) was assessed by six healthy volunteers. The juice ingestion (400 ml) resulted in a significantly increased plasmatic antioxidant capacity after 2 h (30%) and significantly decreased plasma MDA after 4 h (18%). The cumulative urinary excretion of ascorbic acid and anthocyanins was 79 and 0.06% of the ingested amount. From the present findings it can be concluded that various juice antioxidants are variably absorbed and are active as antioxidants in vivo.

Dietary taurine changes ascorbic acid metabolism and cholesterol metabolism in rats fed diets containing polychlorinated biphenyls.

The effect of dietary taurine on ascorbic acid metabolism and hepatic drug-metabolizing enzymes wasinvestigated in rats fed diets containing 0.02% PCB. The rats fed the PCB containing diets showed greater liver weight, and greater activities of drug metabolizing enzymes in the liver than control rats. In PCB-fed rats, urinary ascorbic acid excretion was enhanced, and serum cholesterol concentration (especially HDL-cholesterol) was significantly elevated compared with those in normal rats. Dietary taurine potentiated the increases of urinary excretion of ascorbic acid and the rise in the levels of cytochrome P-450 which were induced by PCB. On the other hand, the supplementation of taurine to normal diet did not alter these parameters. These results suggested that taurine might enhance the hepatic drug-metabolizing systems, leading consequently to the stimulation of the ascorbic acid metabolism in rats fed PCB-containingdiet.

Bioavailability of antioxidative compounds from Brettacher apple juice in humans

The human bioavailability of ascorbic acid and polyphenolics such as chlorogenic acid and caffeic acid resp. from apple juice produced from the polyphenolic rich variety Brettacher was tested. After intake of 700 ml juice the antioxidant capacity in the plasma of human volunteers assessed by the TRAP-test increased significantly by 52% during the following 2 h. The cumulative urinary excretion of ascorbic acid within 7 h after intake was measured to 104% the ingested dose of the juice. Caffeic acid as the intestinal cleavage product of chlorogenic acid was excreted to only 0.56% of the dose in the juice. The results demonstrate in view of the favourable absorptive attributes and the influence on the plasmatic antioxidative capacity of these juice components that Brettacher apple juice may be suitable as a functional food.

Dietary Taurine Alters Ascorbic Acid Metabolism in Rats Fed Diets Containing Polychlorinated Biphenyls

The effect of dietary taurine on ascorbic acid metabolism and hepatic drug-metabolizing enzymes was investigated in rats fed diets containing polychlorinated biphenyls (PCB) to determine whether taurine has an adaptive and protective function in xenobiotic-treated animals. Young male Wistar rats (60 g) were fed diets containing 0 or 0.2 g/kg diet PCB with or without 30 g/kg diet of taurine for 14 d. The rats fed the PCB-containing diets had greater liver weight, higher ascorbic acid concentrations in the liver and spleen and greater hepatic cytochrome P-450 contents than control rats that were not treated with PCB (P < 0.01). In PCB-fed rats, urinary ascorbic acid excretion was enhanced, and serum cholesterol concentration (especially HDL-cholesterol) was significantly elevated compared with those in control rats. Dietary taurine significantly potentiated the increases in the urinary excretion of ascorbic acid and the rise in the levels of cytochrome P-450 which were caused by PCB treatment. On the other hand, the supplementation of taurine to control diet did not alter these variables. Taurine may enhance the hepatic drug-metabolizing systems, leading to the stimulation of the ascorbic acid metabolism in rats fed diets containing PCB.

Amplifying effect of dietary taurine on the induction of cytochrome P-450 and on the urinary excretion of ascorbic acid in rats fed on phenobarbital-containing diets.

Dietary taurine amplified the induction of cytochrome P-450 and the urinary excretion of ascorbic acid in rats fed on phenobarbital (PB)-containing diets. These facts suggest that taurine could influence the hepatic metabolism of xenobiotics via the induction of drug-metabolizing enzymes (DME) and the ascorbic acid metabolism. Taurine might improve the function of DME exposed by some xenobiotics.

EFFECTS OF BIS(4-CHLOROPHENYL) SULFONE ON RATS FOLLOWING 28-DAY DIETARY EXPOSURE

The short-term oral toxicity of a recently identified environmental pollutant, bis(4-chlorophenyl) sulfone (BCPS), was studied. Groups of male Sprague-Dawley rats (n = 6) were administered BCPS via the diet at 0 (control), 10, 100, or 1000 ppm for 4 wk. Additional control and 1000 ppm groups were also treated for 1, 2, and 3 wk. At termination, highdose animals showed depressed growth rate and food consumption, and 1 high dose animal in each of the wk-1, -3, and-4 groups had marked hematuria. Increased liver to body weight ratio was present at 100 ppm and increased kidney to body weight ratio at 1000 ppm. Marked increases in hepatic benzoylresorufin O -dealkylase (BROD) and pentoxyresorufin O-dealkylase (PROD) activities were detected starting at 10 ppm. There was a significant decrease in methoxyresorufin O-dealkylase (MROD) activity at 1000 ppm. Hepatic UDP-glucuronosyltransferase (UDPGT) and glutathione S-transferase (GST) activities also increased starting at 100 ppm. A marked increase in urinary excretion of ascorbic acid was apparent starting at 10 ppm, while there were no changes in urinary N-acetylglucosaminidase (NAG) activity and protein levels. A threefold increase in serum cholesterol and a 30% increase in platelet counts were observed in the 1000 ppm group. Levels of thiobarbituric acid-reactive substances (TBARS) were increased by threefold in the liver of the highdose animals but were not significantly altered in the serum. Tissue BCPS concentrations were dose dependent and followed the order: adipose tissue >> liver > kidneys > brain, spleen, lungs. In the time-course study involving the control and high-dose groups, most of the treatment effects were clearly present in wk 1, and the severity of the effects remained at more or less the same levels thereafter. The exceptions were hepatic BROD and PROD activities, which showed a trend toward further increases with time of treatment. Liver and adipose tissue concentrations of BCPS remained unchanged from wk 1 to wk 4, while kidney concentrations increased with time. The results indicated that BCPS produced hepatic effects at the lowest dose level tested (10 ppm in the diet or 0.8 mg/kg/d).

Administration of Ascorbic Acid and an Aldose Reductase Inhibitor (Tolrestat) in Diabetes: Effect on Urinary Albumin Excretion

The important role of ascorbic acid (AA) as an anti-oxidant is particularly relevant in diabetes mellitus where plasma concentrations of AA are reduced. This study was conducted to evaluate the effects of treatment with AA or an aldose reductase inhibitor, tolrestat, on AA metabolism and urinary albumin excretion in diabetes. Blood and urine samples were collected at 0, 3, 6, 9, and 12 months from 20 diabetic subjects who were randomized into two groups to receive either oral AA 500 mg twice daily or placebo. Systolic and diastolic blood pressures, HbA_1c, plasma lipids, urinary albumin, and total glycosaminoglycan excretion were measured at all time points, and heparan sulphate (glycosaminoglycan) was measured at 0 and 12 months. The same parameters, as well as urinary AA excretion, were determined at 0 and 3 months for 16 diabetes subjects receiving 200 mg tolrestat/day. AA treatment increased plasma AA (ANOVA, F ratio = 12.1, p = 0.004) and reduced albumin excretion rate (AER) after 9 months (ANOVA, F ratio = 3.2, p = 0.03), but did not change the other parameters measured. Tolrestat lowered plasma AA (Wilcoxon’s signed-rank test, p < 0.05), but did not change AER or the other parameters measured. The ability of AA treatment to decrease AER may be related to changes in extracellular matrix or improvement in oxidative defence mechanism. Unlike the rat model of diabetes, inhibition of aldose reductase did not normalize plasma AA or AER in humans. In fact, tolrestat reduced the plasma AA concentration, a phenomenon which may be due to increased utilization of AA. Dietary supplementation of AA in diabetic subjects may have long-term benefits in attenuating the progression of diabetic complications.