Erythrocyte Glutathione Reductase Activity Research Articles

The thiamin, riboflavin and pyridoxine status of patientson emergency admission to hospital

The aim of this study was to assess the prevalence of thiamin, riboflavin and pyridoxinedeficiencies at admission to an acute hospital. One hundred and twenty adult patients were selected at random from those admitted via the Accident and Emergency department over 3 days. Comparisons were made with a group of 80 healthy blood donors sequentially attending a local transfusion centre. The alcohol intake of 500 patients admitted sequentially via the same Accident and Emergency department was also assessed. Erythrocyte transketolase (ETK), glutathione reductase (EGR) and aspartate aminotransferase (EAA) coenzyme activation assays were used to determine thiamin, riboflavin and pyridoxine deficiencies. The prevalences of deficiency states in the inpatient group were 21, 2.7 and 32% for thiamin, riboflavin and pyridoxine deficiencies respectively with 49.2% being deficient in one or more vitamin. The mean alcohol intake in the group of patients in whom this was assessed was 9.7 units per week compared with 10 units per week amongst blood donors.

Glutathione Reductase Activity and Flavin Concentration in Guinea-pig Tissues.

Glutathione reductase (GR) activity and flavin concentration were studied in systemic tissues (brain, heart, lung, liver, spleen, stomach, pancreas, muscle, kidney, testis) and blood components (erythrocytes and plasma) from male guinea-pigs. GR activity and the flavin concentration were high in kidney and liver, and low in muscle. GR activity in erythrocytes was found in a range of tissues, but flavin concentration in erythrocytes was lower than in any tissues. GR was saturated with flavin adenine dinucleotide (FAD) in almost all tissues, but not in muscle or erythrocytes.

Folic acid, riboflavin, thiamine, and vitamin B-6 status of a group of first-time blood donors

Reference intervals for long-term status measures of folate, riboflavin, thiamine, and vitamin B-6 were determined in a select group of adults. Reference subjects had no adverse medical history and did not use tobacco, alcohol, or nutritional supplements, and their diets met > or =70% of the Australian recommended dietary intake for nutrients. Red blood cell concentrations of thiamine and folate were measured by microbiological methods. Vitamin B-6 and riboflavin status were measured on the basis of the erythrocyte aspartate transaminase activity coefficient and erythrocyte glutathione reductase activity coefficient, respectively. A survey of first-time blood donors, which was conducted in Australia in 1995, revealed a significant prevalence of low red blood cell thiamine concentrations (13%) when compared with the calculated normal reference intervals. However, the most important finding in the survey was that the group of healthy, nonanemic adults (first-time blood donors) was found to have a median red blood cell folate concentration 24% below the median concentration of the carefully selected (nonsupplemented) reference group. Plasma total homocysteine concentrations indicated folate deficiency in the reference group. Therefore, the 2.5th percentile cutoff for reference group red blood cell folate concentrations may have underestimated the prevalence of folate deficiency in the survey group. These data, coupled with the lack of Australian food-composition data for folate in particular, reinforce the need for monitoring nutritional status by both dietary and biochemical means. We recommend consideration of mandatory fortification of the Australian food supply with folic acid.

Riboflavin and vitamin B-6 intakes and status and biochemical response to riboflavin supplementation in free-living elderly people

Free-living elderly people aged >65 y were recruited to assess riboflavin and vitamin B-6 intakes and status and the effect of riboflavin supplementation on biochemical indicators of these 2 vitamins. The status of riboflavin (erythrocyte glutathione reductase activation coefficient; EGRAC) and vita-min B-6 (plasma pyridoxal-5'-phosphate; PLP) were determined in a total sample of 92 subjects, from whom dietary intake data were obtained by using the diet history method (n = 83). Although dietary intakes of both vitamins were considered to be adequate according to current reference values, abnormal EGRAC and plasma PLP values were identified in 49% and 38% of subjects, respectively, with 21% having suboptimal status for both nutrients. A subgroup of subjects from the initial sample (n = 45) was assigned in a double-blind manner to receive either 1.6 or 25 mg riboflavin or placebo daily for 12 wk. In those subjects with a baseline EGRAC or plasma PLP value falling outside the currently accepted threshold value for adequacy, low- dose riboflavin supplementation improved status of the limiting nutrient significantly (P <0.0001 and P = 0.020 for EGRAC and plasma PLP responses, respectively). We conclude that a high proportion of healthy elderly people may have suboptimal status for these nutrients despite apparently adequate dietary intakes. Furthermore, we showed that riboflavin supplementation at physiologic doses corrects biochemical abnormalities of not only EGRAC, but also plasma PLP, confirming the biochemical interdependency of these vitamins and suggesting that riboflavin is the limiting nutrient. Am J Clin Nutr 1998;68:389–95.

Enhanced oxidative damage in cystic fibrosis patients.

Antioxidant depletion and increased free radical production by inflammatory cells have been described in cystic fibrosis (CF) patients. To evaluate oxidative damage intensity, we measured plasma concentrations of malondialdehyde, hydroperoxides and protein carbon groups as markers of oxidative injury to lipids and proteins in a group of 101 CF patients free of acute exacerbation, and in 43-112 controls. Moreover, we estimated antioxidant function by measuring activities of erythrocyte superoxide dismutase, glutathione reductase and vitamin E concentrations. In CF patients, malondialdehyde and hydroperoxide plasma levels were significantly higher than in controls (p < 0.001). Increased lipid peroxidation was documented by these two markers. Parallel rises in protein carbonyls in plasma of CF patients were observed (p < 0.0001). These patients presented biochemical but not clinical vitamin E deficiency. Glutathione reductase and superoxide dismutase activities were significantly higher than in controls. These results show a serious imbalance of CF patients between oxidant-antioxidant status leading to oxidative stress.

Antioxidant defence of red blood cells and plasma in stored human blood

Blood collected routinely from donors, and preserved with CPDA-1 anticoagulant (citrate, phosphate, dextrose, adenine), was investigated. The concentration of reduced glutathione, and glutathione peroxidase, glutathione S-transferase, glutathione reductase, superoxide dismutase, and catalase activities in erythrocytes, as well as the total radical-trapping antioxidant parameter in plasma were determined on days 1, 3, 7, 12, 16, 20 and 25 of storage. At the end of the study, a 30% decrease in the reduced glutathione concentration ( P<0.001) and decreases in glutathione S-transferase (over 20%, P<0.001), glutathione reductase (over 8%, P<0.01) and superoxide dismutase (over 10%, P<0.001) activities in erythrocytes, together with up to a 30% diminution of total antioxidant activity in plasma ( P<0.001) were noted. Thus, during blood storage, glutathione-dependent antioxidant systems in erythrocytes and antioxidant defence in plasma are depleted. From the present study, a twelve-day period can be considered a safe storage limit. The sequence of events occurring in stored blood, leading to peroxidative injury in erythrocytes, is discussed.

Effects of sex hormones and antihormones on the activity of redox system enzymes of human erythrocyte glutathione

Effects of estradiol and testosterone and of the antiandrogens cyproterone acetate, niftolide, and antiestrogen tamoxifen on the activities of human erythrocyte glutathione peroxidase and glutathione reductase were studiedin vitro. In contrast to hormone preperations, antihormones in high concentrations (10−4−5×10−4 M) modified the enzyme activities. Cyproterone acetate and tamoxifen increased the activity of glutathione reductase, while tamoxifen stimulated glutathione reductase and inhibited glutathione peroxidase. Niftolide inhibited both enzymes.

Effect of magnesium deficiency on vitamin B2 and B6 status in the rat.

The present study was undertaken to investigate the effect of dietary magnesium (Mg) deficiency on vitamin B2 (riboflavin) and B6 (pyridoxine) status in rats.We fed Wistar rats an Mg-deficient diet (56 mg magnesium per kg food) for 70 days. On days 21, 35 and 70 we measured Mg and manganese (Mn) in plasma and whole blood, alkaline phosphatase in plasma, erythrocyte glutathione reductase activity coefficient (AC-EGR) for riboflavin status, and erythrocyte aspartase transaminase activity coefficient (AC-EAST) for vitamin B6 status.Intake of the Mg-deficient diet significantly decreased plasma and whole blood levels of Mg and plasma alkaline phosphatase activity on all sampling days. The Mg deficit had no effect on plasma concentrations of Mn, but significantly increased whole blood levels of this element on days 35 and 70. The Mg-deficient diet had no effect on AC-EGR, and thus appeared not to affect riboflavin status. However, AC-EAST was significantly increased on day 70, implying that the animals were at risk for vitamin B6 deficiency.Mg deficiency impairs vitamin B6 status by depleting intracellular Mg and thus inhibits the activity of alkaline phosphatase, a metalloenzyme required for the uptake of pyridoxal phosphate by tissues. Although part of the intraerythrocyte loss of Mg is countervailed by Mn, which can act as a substitute activator of alkaline phosphatase, the degree of compensation is insufficient to fully offset the decrease in activity caused by Mg depletion.

Zum einfluss einer unterschiedlich hohen riboflavinversorgung in der gravidität und laktation auf leistungsparameter und die aktivität der erythrozytären glutathion‐reduktase von ratten

In zwei Versuchen mit insgesamt 160 weiblichen Sprague‐Dawley‐Ratten wurde der Einfluß einer unterschiedlich hohen alimentären Riboflavinversorgung während der Laktation und während Gravidität und Laktation auf die Parameter Futteraufnahme, Körpermasseentwicklung, Reproduktionsleistung, hämatologische Parameter und den Aktivitätskoeffizienten der erythrozytären Glutathion‐Reduktase (EGR‐AC) untersucht. Während im ersten Versuch zu einem halbsynthetischen, riboflavinarmen Futter auf Stärke‐Casein‐Basis nur während der Laktation unterschiedliche Riboflavinzulagen gegeben wurden (0, 2, 4, 6, 8, 10, 12, 40, 400, 4000 mg Riboflavin/kg Futter) wurden im zweiten Versuch zwei Zulagestufen während der Gravidität (1, 20 mg Riboflavin/kg Futter) mit drei Zulagestufen während der Laktation kombiniert (1, 5, 20 mg Riboflavin/kg Futter). Beide Versuche dauerten bis zum 14. Laktationstag. Die Futteraufnahme war bei den Tieren ohne Riboflavin‐Supplementierung um 25%, bei der Zulage von 1 mg/kg Futter um 11% im Vergleich zu den höheren Zulagen signifikant verringert. Die Körpermasse wurde in den gleichen Gruppen signifikant um 11% bzw. 4% reduziert. Einflüsse hinsichtlich der Parameter der Reproduktionsleistung zeigten sich nur in der Wurfmasse am 14. Laktationstag, wobei sich hierbei lediglich die Riboflavinversorgung in der Laktation auswirkte. Unterschiede bei den hämatolo‐gischen Parametern waren in keinem der beiden Versuche zu beobachten. Der EGR‐AC war bei einer Riboflavinzuläge von 0 bzw. 1 mg/kg Futter signifikant auf Werte von 1,90 bzw. 1,80 erhöht. Ab einer Zulage von 4–5 mg Ribloflavin zum Futter erreichte der Aktivitätskoeffizient ein Plateau von 1,45, das auch durch höhere Zulagen nicht mehr verbessert werden konnte. Innerhalb des gesamten Reproduktionszyklus (Versuch II) überwog der Einfluß durch die aktuelle Versorgung während der Laktation auf den Parameter EGR‐AC, jedoch zeigte sich, daß eine Riboflavin‐Mangelversorgung während der Gravidität selbst durch eine bedarfsdeckende Versorgung in der Laktation nicht vollständig ausgeglichen werden konnte. Aus diesem Grund wird eine optimale Versorgung mit Ribloflavin während des gesamten Reproduktionszyklus empfohlen. Mit Hilfe des EGR‐AC wurde auch der Riboflavinbedarf laktierender Ratten abgeleitet und bei Verfütterung eines semisynthetischen Futters (17,4 MJ ME/kg DM, 20,8% Rohprotein in DM) Zulagen von 5–6 mg Riboflavin/kg Futter oder eine gesamte Versorgung von 6–7 mg/kg Futter empfohlen.

Relationships between micronutrient intake and biochemical indicators of nutrient adequacy in a "free-living' elderly UK population.

Nutritional assessments are frequently based on amounts of nutrients consumed. In the present paper the usefulness of nutrient intake data for assessing nutrient adequacy is examined in an elderly British population. Subjects were "free-living' elderly aged 68-90 years (sixty men, eighty-five women) in Norwich. Forty-two of forty-nine surviving males and sixty-seven of seventy-nine surviving females were reassessed after 2 years. With few exceptions, estimated micronutrient intake was not statistically predictive of biochemical measures of nutrient adequacy. Initial biochemical measures of nutritional adequacy were compared with those found 2 years later in an attempt to assess whether initial biochemical assessment was predictive of the "longer term' situation. Biochemical measurements at the start of the study were correlated to the same measurements made 2 years later for: serum ferritin, haemoglobin and erythrocyte count, whole-blood Se-glutathione peroxidase (EC 1.11.1.9; males only), plasma Cu, alkaline phosphatase (EC 3.1.3.1), ascorbic acid, vitamin B6 (pyridoxal-5-phosphate), folate and vitamin B12, total erythrocyte thiamin (males only), riboflavin (erythrocyte glutathione reductase (EC 1.6.4.1) activation coefficient): but not for: erythrocyte Cu-superoxide dismutase (EC 1.15.1.1) or plasma Zn. Either only small changes, or no changes, in mean values were seen over the 2 years for most of the biochemical measures. One exception was a large increase in plasma folate. The only important "negative' features seen at 2-year follow up were a large fall in serum ferritin concentration and a large increase in the activity of two antioxidant defence enzymes, superoxide dismutase and glutathione peroxidase. As judged by currently accepted biochemical deficiency threshold values, a small proportion of subjects were possibly at risk of Fe (3% men; 1% women), folate (7%, 3%), thiamin (12%; 3%) and vitamin C (15%; 17%) deficiency. Many more appeared to be at risk of vitamin B6 (42%; 47%) and riboflavin (77%; 79%) deficiency. It was concluded that the requirements of the elderly for vitamins B1, B2 and C, and the biochemical deficiency threshold values used to indicate vitamin B6 deficiency, need review.

The Effect of FAD on Erythrocyte Glutathione Reductase Activity in Undialyzed Uremic Patients and Healthy Subjects

The eryrocyte glutathione reductase (GSSG-R) activity with and without FAD supplementation (Act. A and Act B, respectively) was studied in 24 undialyzed uremic patients and 25 healty subjects. Mean erytrocyte GSSG-R activity from normal subjects was 5039+-1.43 U/g Hb (the active form). After the addition of FAD to the hemolysates, this increased to 7.79+-1.07 U/g Hb, an increase of 1.88+-0.84 U/g Hb (the inactive from) (p

Cadmium-Induced Lipid Peroxidation and the Antioxidant System in Rat Erythrocytes : the Role of Antioxidants

Cadmium (Cd)-induced oxidative damage in erythrocytes causes loss of membrane function by enhancing lipid peroxidation (LPO) and altering the erythrocyte antioxidant system. Vitamin E and/or selenium (Se) was administered to rats, prior to Cd intoxication, in order to prepare the animals to withstand oxidative assault. The treatment with Cd increased LPO in erythrocytes while animals pretreated with vitamin E and/or Se prior to Cd treatment showed decreased LPO as compared with animals given Cd alone. The erythrocyte SOD and CAT activities decreased significantly with Cd treatment. The pretreatment with vitamin E and/or Se prior to Cd administration partially reversed such changes. The erythrocytes showed a marked depletion in glutathione (GSH) content with Cd treatment. The antioxidant treatments before Cd administration helped to maintain the erythrocyte GSH content. The erythrocyte glutathione reductase (GSH-R) activity increased markedly when treatments with vitamin E and Se were applied. The GSH-R activity was not observed to decrease in animals treated with antioxidant prior to Cd intoxication, which may mean that the replenishment of erythrocyte GSH content is via GSH-R. The glutathione-S-transferase (GST) activity increased significantly with Cd intoxication; however, treatment with antioxidants prior to Cd treatment decreased erythrocyte GST activity. The results show that Cd-induced LPO decreased the antioxidant capability of the erythrocytes, causing erythrocyte membrane damage.

Glutathione reductase activity, riboflavin status, and disease activity in rheumatoid arthritis.

To measure erythrocyte glutathione reductase (EGR) activity and riboflavin status, and their relations to disease activity, in rheumatoid arthritis patients compared to healthy controls. Patients with rheumatoid arthritis were classified as active if there were features of articular inflammation which required initiation or change of disease modifying therapy, and as inactive if they had little evidence of articular inflammation. EGR was measured in patients and healthy controls by a functional assay with or without the addition of flavin adenine dinucleotide (FAD). The ratio of stimulated EGR (with FAD added) to basal EGR (no added FAD), which measures riboflavin status, is known as the EGR activation coefficient (EGRAC). An EGRAC > or = 1.3 represents biochemical riboflavin deficiency. 91 patients with rheumatoid arthritis, including 57 with active disease, and 220 healthy controls were studied. Both basal and stimulated EGR were significantly higher in patients with rheumatoid arthritis (P = 0.0001) than in controls. Biochemical riboflavin deficiency was identified in 41% controls and 33% patients with active rheumatoid arthritis but was significantly less frequent (9%) in patients with inactive compared to active disease (P = 0.02) or healthy controls (P = 0.0006). Pain score, articular index, C reactive protein, and erythrocyte sedimentation rate were increased in patients with riboflavin deficiency (all P < 0.02). Higher basal and stimulated EGR might be expected in patients with rheumatoid arthritis in response to chronic oxidative stress due to synovial inflammation. The association of riboflavin deficiency with increased disease activity suggests that impaired EGR activity could facilitate continuing inflammation in these patients.

The Riboflavin Requirement of Adult Dogs at Maintenance Is Greater than Previous Estimates

A study was conducted to determine the riboflavin requirement of adult dogs at maintenance. Twenty adult mixed breed dogs were fed a semipurified meal with one of five riboflavin concentrations: Diet 1, 1.7 mg/kg; Diet 2, 2.7 mg/kg; Diet 3, 3.7 mg/kg; Diet 4, 4.7 mg/kg; and Diet 5, 5.7 mg/kg. The erythrocyte glutathione reductase activity coefficient (EGRAC) was used to determine biochemical riboflavin deficiency. Dogs fed Diet 1 had a greater (P < 0.05) EGRAC (1.24) on d 56 of the trial compared with that of dogs fed Diet 5 (1.11), indicating marginal riboflavin deficiency in dogs fed Diet 1. On d 84 the mean EGRAC for dogs fed Diet 1 (1.36) was different from EGRAC obtained for dogs fed the other diets (1.19, P < 0.05). This difference in mean EGRAC was still present on d 112 (1.59 vs. 1.27; P < 0.01). There was no difference in d 112 mean EGRAC for dogs fed Diets 2, 3, 4 and 5 (P < 0.05). The broken line requirement estimate for the adult dog at maintenance was determined to be 66.8 µg riboflavine · kg body wt-1 · d-1 using the d 112 EGRAC as the basis for assessing biochemical riboflavin deficiency.

Riboflavin nutrition of sows.

Two experiments were conducted to evaluate the response of sows to high levels of dietary riboflavin. Responses evaluated were erythrocyte glutathione reductase activity coefficient (EGRAC, a biochemical indicator of riboflavin status) and reproductive performance. In Exp. 1, eight sows were fed diets either slightly deficient or superadequate in riboflavin throughout a reproductive cycle, beginning in midgestation. The EGRAC values confirmed the slight deficiency (P < .01) but did not clearly show a time when the sow is most likely to be deficient in riboflavin. In Exp. 2, 118 sows at two farms were fed diets providing 10 (control, 1.4 times the NRC [1988] requirement estimate), 60, 110, or 160 mg of riboflavin/d for 21 d beginning at breeding, and the control level through the remainder of the reproductive cycle. The percentage of sows farrowing tended to be lower (P < .10) for the control sows than for sows fed the other treatments (66.7, 85.7, 93.3, and 86.7% for 10, 60, 110, and 160 mg/d, respectively). This response is similar to other results reported previously. No other measure of reproductive performance nor EGRAC measured at any of five stages of the reproductive cycle, was affected by treatment. These results suggest that massive riboflavin supplementation of the sows' diet during early pregnancy may increase the percentage of farrowing but does no increase litter size.

Protective effects of antioxidants against uraemia-induced lipid peroxidation and glutathione depletion in humans.

The effects of uraemias and antioxidant therapy for 40 days with vitamin A, vitamin C and vitamin E on blood and erythrocyte sulfhydryl (glutathione, GSH) content and on erythrocyte glutathione-S transferase (GST), glutathione reductase (GSR) and glutathione peroxidase activities were studied in six uraemic patients maintained on haemodialysis. In addition, the effect of antioxidant therapy on erythrocyte lipid peroxidation was determined, and erythrocyte haemoglobin content was measured. Uraemic patients in dialysis exhibited significant decreases in blood and erythrocyte GSH content as well as significant decreases in the activities of GST, GSR and GSH-peroxidase relative to control subjects. Furthermore, the uraemic patients had elevated erythrocyte malondialdehyde levels. Blood and erythrocyte GSH content from uraemic patients was significantly elevated after 20 days of antioxidant treatment and remained elevated thereafter throughout the remaining 20 days of the study (130% and 173%, respectively). Antioxidant therapy also produced significant increases in GSR and GSH-peroxidase activities after 20 days of treatment which remained relatively constant thereafter. No significant change in GST activity was observed. Erythrocyte malondialdehyde levels, as an index of oxidative tissue damage, exhibited a significant decrease (70%) in the patients after 40 days of antioxidant therapy. A gradual increase in erythrocyte haemoglobin content was observed following treatment of the uraemic subjects (45% at day 40). The results suggest that antioxidant therapy may protect against oxidative stress associated with uraemia.

Selenium and training effects on the glutathione system and aerobic performance

Changes in blood glutathione antioxidant system in response to exercise and training, and aerobic performance, were investigated. Selenium (Se) supplementation effects on these changes were evaluated. The study was double blind. Both groups selenium (Sel, N = 12) and placebo (Pla, N = 12), followed a 10-wk endurance training program, with a prolonged exhaustive exercise bout performed (Cap Max), before (Pre) and after (Post) training. Blood was sampled before (Bef) and after (Aft) Cap Max. The oxidation of blood glutathione after Cap Max exercise showed a reactive oxygen species production. Training developed maximal aerobic power and capacity, significantly increased (P < 0.001) plasma and erythrocyte glutathione peroxidase (GPx) activity, and decreased (P < 0.001) erythrocyte glutathione reductase activity. The Se supplementation caused an increase in the basal plasma GPx level (P < 0.05). There was also a correlation (r = 0.66, P < 0.05) between the variation in VO2max and that of erythrocyte GPx only in supplemented subjects. Our results confirm that blood glutathione remains a sensitive marker of oxidative stress induced by exhausting submaximal exercise and that the antioxidant potential of GPx can be developed by endurance training. Se supplementation at the dose used had no effect on physical performance.

No evidence for inhibition of human glutathione reductase by valproic acid

The human red blood cell enzyme glutathione reductase (GR) was reported to be inhibited by the anticonvulsant drug valproic acid (VPA) [Cotariu et al., Biochem Pharmacol 43: 425–429, 1992]. When attempting to reproduce and extend these experiments, we could not detect any significant effect of VPA on glutathione reductase in haemolysates from 20 healthy children and 10 children under VPA therapy, no matter which concentration of the drug (0.9 or 1.8 mM in a haemolysate diluted by a factor of 50 or 1.8 mM directly in the assay), which incubation time (0–60 min) and which assay system were chosen. An influence of VPA on FAD-free apoglutathione reductase was also excluded. GR-activities of 10 children under VPA therapy (1.08 ± 0.14 U/mL blood or 7.57 ± 0.94 U/g Hb) were almost identical with the activities of age- and sex-matched controls (1.04 ± 0.17 U/mL or 7.79 ± 1.32 U/g Hb). No correlation between erythrocyte GR activity and serum levels of VPA was observed. Finally, incubation of crystalline human GR with VPA did not lead to enzyme inhibition; rather, in most experiments the enzyme was stabilized by incubation with VPA. Possible explanations for the discrepancies between the results of Cotariu et al. and our data are discussed.

Enhanced growth of mammary adenocarcinoma in rats by chloroquine and quinacrine

This study investigated whether the growth of transplanted mammary tumors is altered in rats by treatment with the antimalarial drugs chloroquine (CQ) and quinacrine (QN). Female inbred F344 rats were divided into three experimental groups. Animals were injected i.p. with either CQ, QN or normal saline for 5 days a week throughout the entire experimental period (25 days). After 7 days of drug treatment each rat received subcutaneously one 2-mm 2 aliquot of R3230AC mammary adenocarcinoma in the mid-thoracic region. Eighteen days after implantation, all rats were sacrificed and tumors were excised, weighed and measured. The results indicate that weights and volumes of tumors as well as tumor-to-body weight ratios were significantly higher in CQ and QN-treated animals than those in saline-treated animals. The final body weights of rats treated with QN were significantly lower than those treated with saline. The prostaglandin E 2 content of tumors was significantly reduced by CQ treatment. Erythrocyte glutathione reductase activity coefficient and reduced glutathione concentrations remained unaffected by both treatments. These results suggest that CQ and QN have significant stimulatory effects on the growth of mammary adenocarcinoma in rats.

Relative bioavailability of riboflavin in cows' milk and fermented milk using rat bioassay

Abstract Bioavailability of riboflavin from cows' milk and fermented milk was assessed using riboflavin-depleted rats. The fermented milk was prepared using Lactococcus lactis subsp. lactis, and cremoris and Propionibacterium shermanii as starter cultures. Rats were depleted of riboflavin by feeding a riboflavin-free diet for 30 days. At this stage, hepatic riboflavin and erythrocyte glutathione reductase (EGR) activity decreased significantly (P Relative bioavailability (RBV), relative to pure vitamin, of riboflavin from milk and fermented milk was determined by slope ratio statistics using multiple linear regression with hepatic riboflavin, EGR activity and AC on FAD addition as response criteria. RBV for milk and fermented milk were 144 and 161% with hepatic riboflavin as a response criterion, 135 and 154% with EGR activity as a criterion and 116 and 125% with AC as a criterion. RBVs were significantly greater for milk and fermented milk than for the pure vitamin.