Differential effects of grape juice on gastric emptying and renal function from cisplatin-induced acute adverse toxicity.

Grape skin and seeds contain large amounts of phytochemicals such as polyphenols, resveratrol, and proanthocyanidins, which possess antioxidant activities. Cisplatin is widely used in the treatment of cancer. High doses of cisplatin have also been known to produce acute adverse effects. The aim of this study was to investigate the protective effects of antioxidant properties of whole grape juice (with skin and seeds) on cisplatin-induced acute gastrointestinal tract disorders and nephrotoxicity in Wistar rats. Gastric emptying is significantly increased in whole grape juice-pretreated rats when compared to cisplatin treatment alone. The expression of ghrelin mRNA of stomach is increased in rats with whole grape juice. However, pretreatment with whole grape juice did not reduce renal function markers in acute renal toxicity. No significant changes were recorded in the oxidative stress/antioxidant status parameters of any study group. In contrast, pretreatment with whole grape juice slightly improved tubular cell vacuolization, tubular dilatation, and cast formation in renal tubules. These results show that consumption of whole grape juice induces somewhat beneficial effects in preventing cisplatin-mediated dyspepsia but does not offer protection against cisplatin-induced acute renal toxicity.

Playing saxophone induced diffuse alveolar hemorrhage: a case report.

INTRODUCTION: The blood-gas barrier must be very thin to allow gas exchange and it is therefore subjected to high mechanical stresses when the capillary pressure rises. Exercise-induced pulmonary hemorrhage (EIPH) occurs frequently in horses and there is evidence that EIPH can also occur in humans. MATERIALS AND METHODS: We reported on a healthy 65-year-old male who developed a diffuse alveolar hemorrhage (DAH), like an EIPH, after playing saxophone for 6 h continuously. There were hemoptysis, crackles breathing sounds on exam, and bilateral radiographic infiltrates. A high-resolution computed tomographic study of the thorax disclosed DAH, the presence of which was proved by a gross appearance of bilateral bronchus on bronchoscopy and histopathological study of bronchoalveolar lavage material. CONCLUSION: This is the first report of alveolar hemorrhage caused by playing saxophone. In our case, he presented with a benign course and regressed spontaneously without any medical intervention.

Contribution of peroxynitrite to fatal cardiovascular depression induced by overproduction of nitric oxide in rostral ventrolateral medulla of the rat.

We evaluated the contribution of peroxynitrite to the fatal cardiovascular depression induced by overproduction of nitric oxide (NO) after activation of inducible NO synthase (iNOS) in the rostral ventrolateral medulla (RVLM), the origin of sympathetic vasomotor tone. In Sprague-Dawley rats maintained under propofol anesthesia, microinjection of E. coli lipopolysaccharide (LPS) bilaterally into the RVLM elicited significant hypotension, bradycardia, reduction in sympathetic vasomotor tone and mortality. There was also a discernible elevation of iNOS expression in the ventrolateral medulla, followed by a massive production of nitrotyrosine, an experimental index for peroxynitrite. Co-administration bilaterally into the RVLM of the selective iNOS inhibitor, S-methylisothiourea (50, 100 or 250 pmol), an active peroxynitrite decomposition catalyst, 5,10,15,20-tetrakis- (N-methyl-4'-pyridyl)-porphyrinato iron (III) (10 or 50 pmol), a peroxynitrite scavenger, L-cysteine (5, 50 or 100 pmol), or a superoxide dismutase mimetic, Mn(III)-tetrakis-(4-benzoic acid) porphyrin (1 or 10 pmol), significantly prevented mortality, reduced nitrotyrosine production and reversed the NO-induced cardiovascular suppression after application of LPS into the RVLM. We conclude that the formation of peroxynitrite by a reaction between superoxide anion and NO is primarily responsible for the fatal cardiovascular depression induced by overproduction of NO after activation of iNOS at the RVLM.

Dietary fat and garlic oil independently regulate hepatic cytochrome p(450) 2B1 and the placental form of glutathione S-transferase expression in rats.

The individual and combined effects of dietary fat and garlic oil on two drug-metabolizing enzymes, cytochrome P(450) 2B1 and the placental form of glutathione (GSH) S-transferase (PGST), in rat liver were examined in this study. Rats were fed a low corn oil, high corn oil or high fish oil diet and received various amount of garlic oil (0, 30, 80, 200 mg/kg body) orally three times per week for 6 wk. The fat energy in the low and high fat diets accounted for 11.6 and 45.7% of total energy, respectively. Final body weights did not differ among the three dietary fat groups and were not affected by garlic oil treatment. The fatty acid profile in hepatic phospholipids revealed higher eicosapentaenoic acid [20:5(n-3)] and docosahexaenoic acid [22:6(n-3)] levels in the fish oil-fed group than in the low and high corn oil-fed groups (P < 0.05). In contrast, the corn oil-fed groups had greater hepatic phospholipid arachidonic acid [20:4(n-6)] levels (P < 0.05). Both dietary fat and garlic oil significantly affected hepatic cytochrome 7-pentoxyresorufin O-dealkylase (PROD) activity and GST activity toward ethacrynic acid. Rats fed the high fish oil diet had 85 and 51% higher PROD activity compared with those fed the low or the high corn oil diet, respectively (P < 0.05). The GST activity in the high fish oil and the high corn oil groups was 33 and 18% higher than that in the low corn oil group (P < 0.05), respectively, and the GST activity in rats fed the high fish oil diet was higher than in those fed the high corn oil diet (P < 0.05). Garlic oil dose-dependently increased GST activity. No interaction between dietary fat and garlic oil on PROD or GST activity was noted. Northern and Western blot analysis revealed that dietary fish oil increased both cytochrome P(450) 2B1 and PGST mRNA and protein levels. Cytochrome P(450) 2B1 and PGST mRNA and protein levels were also dose-dependently increased by garlic oil treatment. The effects of garlic oil and dietary fat on P(450) 2B1 and PGST mRNA and protein expression were independent. These results indicate that dietary fat and garlic oil independently modulate P(450) 2B1 and PGST expression at transcriptional and/or post-transcriptional stages.

Nutritional status of functionally dependent and nonfunctionally dependent elderly in Taiwan.

OBJECTIVE: The purpose of this study was to measure and compare nutritional status of the functionally dependent elderly with those nonfunctionally dependent elderly by assessing nutrient intake, anthropometric measurements, hematological and biochemical parameters, and the nutritional risk index (NRI). METHODS: Ninety-six volunteers (42 functionally dependent elderly, 54 nonfunctionally dependent elderly) participated in this study. The items of activity of daily living (ADL) were assessed to determine functional status. Demographic and health data were collected at the time of interview. Subjects completed 24-hour diet recall and food frequency questionnaires. Height, weight and skinfold thickness measurements were taken. Hematological and biochemical parameters were measured. The NRI was then calculated. RESULTS: Osteoporosis and hypertension were the most frequently reported chronic diseases. A small proportion of the elderly with functional dependence (9.5%) and with nonfunctional dependence (13%) had a body mass index (BMI) (< or = 21 kg/m2), indicating they were underweight. There were no significant differences in nutrient intake between the two groups. However, a higher percentage of the functionally dependent elderly had a nutrient intake of less than 75% of the Taiwan Recommended Daily Nutrient Allowance (RDNA). The functionally dependent group had a higher prevalence of malnutrition than the nonfunctionally dependent group (44.7% vs. 25%) based on the NRI. CONCLUSIONS: These functionally dependent elderly people exhibited a poorer nutritional status than the nonfunctionally dependent elderly. The elderly with functional dependence were at risk for inadequate iron intake and abnormal serum triglyceride concentrations: they were also at greater risk for chronic diseases and had a greater need for medications.

Comparison of the effect of fish oil and corn oil on chemical-induced hepatic enzyme-altered foci in rats.

The effects of fish oil and corn oil diets on diethylnitrosamine initiation/phenobarbital promotion of hepatic enzyme-altered foci in female Sprague-Dawley rats were investigated. Groups of 12 rats were initiated with diethylnitrosamine (15 mg/kg) at 24 h of age. After weaning, they received diets containing either 13.5% fish oil plus 1. 5% corn oil or 15% corn oil for 24 weeks. Rats fed fish oil had significantly greater liver weight, relative liver weight, spleen weight, and relative spleen weight than rats fed corn oil (p < 0.05). Hepatic phospholipid fatty-acid profile was significantly affected by the type of dietary lipid. The rats fed fish oil had significantly greater hepatic phospholipid 20:5 and 22:6 than rats fed corn oil; in contrast, the rats fed corn oil had significantly greater hepatic phospholipid 18:2 and 20:4 than rats fed fish oil (p < 0.05). Rats fed fish oil had significantly lower hepatic vitamin E and PGE(2) content but significantly greater hepatic lipid peroxidation than rats fed corn oil (p < 0.05). The hepatic levels of antioxidant enzymes (GSH reductase and GST) were significantly greater in rats fed fish oil than in rats fed corn oil (p < 0.05). Except for PGST-positive foci (foci area/tissue area), all the other foci parameters (GGT-positive foci area/tissue area, GGT-positive foci no./cm(2), GGT-positive foci no./cm(3), PGST-positive foci no. /cm(2), and PGST-positive foci no./cm(3)) measured in the fish oil group were 10-30% of those in the corn oil group (p < 0.05). Analyses of Pearson correlation coefficient revealed a positive correlation between hepatic GGT- or PGST-positive foci number (no. /cm(2)) and PGE(2) content (r = 0.66, P = 0.01; r = 0.56, P = 0.02, respectively) but a negative correlation between GGT- and PGST-positive foci (no./cm(2)) and lipid peroxidation (r = -0.8, P = 0.0006; r = -0.58, P = 0.01, respectively), GSH/(GSH + GSSG) ratio (r = -0.61, P = 0.05; r = -0.4, P = 0.14, respectively), GSH reductase (r = -0.75, P = 0.002; r = -0.53, P = 0.02, respectively), and GST activities (r = -0.65, P = 0.01; r = -0.44, P = 0.07, respectively). Similar correlation between foci number (no./cm(3)) and PGE(2), lipid peroxidation, GSH/(GSH + GSSG) ratio, GSH reductase, and GST activities were obtained. The results of this study show that dietary fish oil significantly inhibited hepatic enzyme-altered foci formation compared with corn oil in rats. These results suggest that the possible mechanisms involved in this process are the stimulation of hepatic detoxification system, changes in membrane composition, inhibition of PGE(2) synthesis, the enhancement of GSH-related antioxidant capacity, and the enhancement of lipid peroxidation by fish oil.

Autoantibody against oxidized low-density lipoproteins may be enhanced by cigarette smoking.

A total of 59 healthy male subjects (32 smokers and 27 nonsmokers) who had no reported systemic disease and did not take alcohol and vitamin supplementation were included. The levels of autoantibody to oxidized low-density lipoproteins (ox-LDL) in smokers and age-matched nonsmokers were compared. The plasma levels of antioxidants that can affect the formation of ox-LDL were also measured, and correlation analyses between anti ox-LDL IgG and plasma antioxidants, controlling for age and body mass index (BMI), were performed. Plasma alpha-tocopherol and uric acid concentrations of nonsmokers (2.78+/-1.09 microg/mg total lipid and 6.96+/-1.69 mg/dl, respectively) were significantly higher than those of smokers (1.68+/-0.48 microg/mg total lipid and 6.15+/-1.14 mg/dl, respectively) (P<0.05). Although plasma ascorbate and retinol levels were not significantly different between smokers and nonsmokers, smokers older than 45 years old had significantly lower plasma ascorbate levels (0.32+/-0.17 mg/dl) than age-matched nonsmokers (0. 53+/-0.14 mg/dl) (P=0.036). Higher level of plasma anti ox-LDL IgG was noted in the group of smokers compared with nonsmokers (515+/-409 mU/ml vs. 407+/-268 mU/ml, respectively) under the statistic method of Chi-Square test (P=0.049). A significant negative correlation was found between plasma anti ox-LDL IgG and alpha-tocopherol in the combined population as well as in the smoker group (r=-0.26, p=0.047; r=-0.48, p=0.006; respectively). However, there was no correlation between plasma anti ox-LDL IgG and the levels of other antioxidants. These results suggest that reduced concentrations of alpha-tocopherol are associated with cigarette smoking. The significantly negative correlation between plasma anti ox-LDL IgG and alpha-tocopherol in the entire study population as well as in the smoker group suggests that plasma alpha-tocopherol may be partially effective if not totally at protecting LDL from oxidative damage caused by cigarette smoking and dietary supplementation with alpha-tocopherol may provide a protective effect against LDL oxidation, especially in smokers.

Suppression of altered hepatic foci development by a high fish oil diet compared with a high corn oil diet in rats.

Effects of low corn oil, high corn oil, and high fish oil diets on altered hepatic foci development in female Sprague-Dawley rats were investigated. Rats assigned to Groups 1-4 were initiated with saline as the control and those assigned to Groups 5-7 were initiated with diethylnitrosamine (DEN 15 mg/kg) at 24 hours of age. After weaning, all rats, except those in Group 1, received 500 ppm phenobarbital (PB) in their diet as tumor promoter for three months. Altered hepatic foci development was significantly lower in DEN-initiated rats fed the high fish oil + PB diet than in DEN-initiated rats fed the high corn oil + PB diets. Liver weight and relative liver weight were significantly greater in rats fed the high fish oil + PB diet than in rats fed the other diets, and hepatic biotransformation/detoxification enzyme activities were greater in rats fed the fish oil + PB diets than in rats fed the other diets. These results suggest that the effect of a high fish oil diet on altered hepatic foci may occur through regulation of hepatic biotransformation/detoxification enzyme activities, leading to alteration in the tumor-promoting action of PB. Dietary lipid significantly affected the hepatic phospholipid fatty acid composition of rats. n-3 polyunsaturated fatty acids were incorporated into membrane phospholipid at the expense of n-6 polyunsaturated fatty acids. A high fish oil diet caused greater oxidative stress in rats, as measured by plasma vitamin E level, red blood cell glutathione status, liver lipid peroxidation, and hepatic glutathione reductase activity. Pearson's correlation analysis indicated that the foci number was negatively correlated to the liver thiobarbituric acid-reactive substance and 7-pentoxyresorufin O-dealkylase activity, and the foci area was negatively correlated to the liver thiobarbituric acid-reactive substance activity (p < 0.05) in rats of groups that developed foci. These results suggest that the type of dietary lipid is the more important determinant for gamma-glutamyl transpeptidase-positive foci development than the amount of dietary lipid when rats consumed approximately the same amount of calories in all the dietary groups, and the underlying mechanisms may be partially ascribed to the antioxidant/oxidation status and biotransformation/detoxification system of rats.

Corn oil enhances gamma-glutamyl transpeptidase-positive foci development in the presence of phenobarbital during hepatocarcinogenesis in rats.

We investigated the effects of type of dietary fat and phenobarbital on gamma-glutamyl transpeptidase-positive foci development. Four groups of six female Sprague-Dawley rats were initiated with diethylnitrosamine (15 mg/kg) at 24 hours of age. After weaning, they were fed nutritionally complete semipurified diets containing 15% corn oil or 5% corn oil + 10% fish oil and supplemented with 5,000 ppm vitamin E with or without phenobarbital (500 ppm) for three months. Dietary fish oil significantly increased hepatic phospholipid eicosapentaenoate and docosahexaenoate concentrations and decreased arachidonate concentration compared with 15% corn oil (p < 0.05). Corn oil (15%) significantly increased hepatic prostaglandin F2 alpha concentration compared with 10% fish oil (p < 0.05). Phenobarbital significantly stimulated glutathione S-transferase activity in both dietary fat groups (p < 0.05). In the absence of phenobarbital, type of dietary fat showed no effect on hepatic gamma-glutamyl transpeptidase-positive foci development. However, in the presence of phenobarbital, 15% corn oil significantly enhanced gamma-glutamyl transpeptidase-positive foci development compared with 10% fish oil (p < 0.05). Phenobarbital showed a strong tumor-promoting action in both dietary groups. In conclusion, there was an interaction between type of dietary fat and phenobarbital on gamma-glutamyl transpeptidase-positive foci development during hepatocarcinogenesis in rats.

Amount and type of dietary lipid modulate rat hepatic cytochrome P-450 activity.

The influence of the amount and type of dietary lipid on rat hepatic cytochrome P-450 activities in the presence and absence of inducer administration was investigated. Weanling male Sprague-Dawley rats were fed fat-free or 20% beef tallow, olive oil, corn oil, linseed oil, or menhaden oil diets in combination with one of the following three treatments: no inducer, intraperitoneal injection of phenobarbital (75 mg/kg body wt) for three consecutive days before they were killed, or intragastric administration of acetone (5 ml/kg) one day before they were killed. Twenty percent linseed oil and menhaden oil diets induced the highest level of activity among the different fat types in the presence of phenobarbital and acetone. Cytochrome P-450IIB1 activity was induced to a significantly greater extent by acetone administration in conjunction with the 20% menhaden oil diet than in conjunction with the other dietary oils (p < 0.05). In the presence of acetone, 20% beef tallow, 20% linseed oil, and 20% menhaden oil diets significantly induced cytochrome P-450IIE1 activity compared with the fat-free diet (p < 0.05). In conclusion, cytochrome P-450IIB1 and P-450IIE1 activities in rats were significantly increased by specific inducers, and dietary lipid was necessary for this effect. Diets supplemented with linseed and menhaden oils were most effective in inducing this activity.

Plasma vitamins A and E and red blood cell fatty acid profile in newborns and their mothers.

OBJECTIVE: In this work, we have measured the plasma vitamins A and E and red blood cell fatty acid profile in newborns and their mothers and have determined whether there are any relationships between maternal blood and cord blood for the nutrients measured. SETTING: The study was performed at the Chung Shan Memorial Hospital, Taichung, Taiwan. SUBJECTS: Twenty-nine pairs of mothers and their term infants. INTERVENTIONS: Maternal venous blood was collected in the first trimester and at delivery, and cord blood was collected at delivery. Plasma vitamin A and E levels were determined by high performance liquid chromatography and red blood cell fatty acid profile was estimated by gas chromatography. RESULTS: Mothers had significantly greater plasma vitamin A and E levels and vitamin E/total lipid than their term neonates did (P < 0.05). Maternal plasma vitamin E and vitamin E/total lipid were significantly greater in the first trimester than at delivery (P < 0.05). Red blood cell phospholipid oleate and linoleate were significantly greater in maternal red blood cell than in cord blood (P < 0.05), however, stearate and arachidonate were significantly greater in the cord blood than in the maternal blood (P < 0.05). Maternal vitamin E, vitamin E/total lipid, palmitate, linoleate, arachidonate and docosahexaenoate were found positively correlated to those in their neonates (P < 0.05). CONCLUSIONS: The results suggest that there is a relationship between maternal blood and cord blood for some nutrients. Therefore, the nutritional status of mothers may affect the nutritional outcome of their neonates.

Blood pressure-lowering effect of fish oil is independent of thromboxane A2 level in spontaneously hypertensive rats.

Whether the alterations in the synthesis of thromboxane A2 (TXA2) is the direct mechanism underlying the blood pressure-lowering effect of fish oil was investigated in this study. Six groups of 11 male spontaneously hypertensive rats were fed semipurified diets containing corn or fish oils and graded levels (50, 5000 or 15,000 ppm) of dietary vitamin E for 8 weeks. Plasma TXA2, assayed by RIA, was significantly greater in the corn oil group than in the fish oil group (P < 0.05). Compared to 50 ppm dietary vitamin E, 5000 and 15 000 ppm dietary vitamin E, respectively, significantly decreased plasma TXA2 (P < 0.05). Systolic, mean or diastolic blood pressure, evaluated by the tail cuff method, were significantly higher in the corn oil group than in the fish oil group (P < 0.05). However, vitamin E had no effect on blood pressure. No relationship between TXA2 and blood pressure was found. Experimental results indicated that the alterations in the synthesis of TXA2 were not the direct antihypertensive effect of fish oil.

Effects of vitamin E deficiency and dietary linoleate on serum thromboxane synthesis in male sprague-dawley rats.

The aim of the present study was to examine whether vitamin E deficiency and dietary linoleate had additive or synergistic effects on serum thromboxane (TX) status and therefore on thrombogenesis. Eight groups of five male weaning Sprague-Dawley rats were fed semipurified diets containing 3.5 or 18.4% of energy from linoleate (en% linoleate) and 0, 100, 5000, 15,000 ppm vitamin E for 8 weeks. Rats fed no vitamin E had the lowest serum vitamin E while rats fed 15,000 ppm vitamin E had the highest serum vitamin E (p < 0.05). Serum 18:2, n-6 (linoleic acid; LA) and 20:4, n-6 (arachidonic acid; AA) were significantly greater in the 18.4 en% linoleate group than in the 3.5 en% linoleate group (p < 0.05). Serum TXA2, measured as its stable metabolite TXB2, was significantly greater in the vitamin E-deficient rats than in the vitamin E-adequate and vitamin E-supplemented rats (p < 0.05). Serum lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARS), was significantly greater in the 0 and 100 ppm vitamin E groups than in the 5000 and 15,000 ppm vitamin E groups (p < 0.05). No interaction between dietary linoleate and vitamin E deficiency on serum TX status was found. However, it seemed that vitamin E deficiency had a more potent effect on TX synthesis than dietary linoleate. The result suggested that vitamin E deficiency may be prothrombogenic via its effect on TX synthesis.