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ABSTRACT: Postprandial hyperglycemia induces oxidative stress responses, impairs vascular endothelial function (VEF) and increases the risk of cardiovascular disease. We hypothesized that the antioxidant and anti-inflammatory activities of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) would protect against vascular dysfunction that is otherwise caused by postprandial hyperglycemia by decreasing oxidative stress and proinflammatory responses, and improving nitric oxide (NO•) homeostasis. In a randomized, crossover study, healthy men (n=15; 21.8±0.8 years) completed a fasting oral glucose challenge (75 g) with or without prior supplementation of γ-TmT (5 days). Brachial artery flow-mediated dilation (FMD), plasma glucose, insulin, antioxidants, malondialdehyde (MDA), inflammatory proteins, arginine and asymmetric dimethylarginine (ADMA) were measured at regular intervals during a 3-h postprandial period. Supplementation of γ-TmT increased (P<.05) plasma γ-T by threefold and γ-carboxyethyl-hydroxychroman by more than ninefold without affecting α-T, glucose, arginine or ADMA. Baseline FMD, MDA, arginine and ADMA were unaffected by γ-TmT (P>.05). Postprandial FMD decreased 30%-44% (P<.05) following glucose ingestion, but was maintained with γ-TmT. Supplementation of γ-TmT also attenuated postprandial increases in MDA that occurred following glucose ingestion. Plasma arginine decreased (P<.05) in both trials to a similar extent regardless of γ-TmT supplementation. However, the ratio of ADMA/arginine increased time-dependently in both trials (P<.05), but to a lesser extent following γ-TmT supplementation (P<.05). Inflammatory proteins were unaffected by glucose ingestion or γ-TmT. Collectively, these findings support that short-term supplementation of γ-TmT maintains VEF during postprandial hyperglycemia possibly by attenuating lipid peroxidation and disruptions in NO• homeostasis, independent of inflammation.
The Journal of nutritional biochemistry 07/2012; · 4.29 Impact Factor
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ABSTRACT: Previously, we have shown that green tea extract (GTE) lowers the intestinal absorption of lipids and lipophilic compounds in rats. This study was conducted to investigate whether GTE inhibits the intestinal absorption and biliary secretion of benzo[a]pyrene (BaP), an extremely lipophilic potent carcinogen, present in foods as a contaminant. Male rats with lymph or bile duct cannula were infused at 3.0 ml/h for 8 h via a duodenal catheter with lipid emulsion containing (14)C-BaP with or without GTE in PBS buffer. Lymph and bile were collected hourly for 8 h. The (14)C-radioactivities in lymph, bile and intestine were determined and expressed as % dose infused. Results showed that GTE drastically lowered the lymphatic absorption of (14)C-BaP (7.6±3.2% in GTE-infused vs. 14.4±2.7% dose/8 h in control rats), with a significantly higher amount of (14)C-radioactivity present in the small intestinal lumen and cecum in rats infused with GTE. GTE also markedly increased the hourly rate (3.9±0.1% dose/h in GTE-infused vs. 3.0±0.1% dose/h in control rats) and the total biliary secretion of (14)C-BaP (31.5±0.8% dose/8 h in GTE-infused vs. 24.3±0.4% dose/8 h in control rats). The findings provide first direct evidence that GTE has a profound inhibitory effect on the intestinal absorption of BaP and promotes the excretion of absorbed BaP via the biliary route. Further studies are warranted to investigate whether green tea could be recommended as a dietary means of ameliorating the toxicity and carcinogenic effect of BaP.
The Journal of nutritional biochemistry 10/2011; 23(8):1007-11. · 4.29 Impact Factor
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ABSTRACT: Postprandial hyperglycemia induces vascular endothelial dysfunction (VED) and increases future cardiovascular disease risk. We hypothesized that postprandial hyperglycemia would decrease vascular function in healthy men by inducing oxidative stress and proinflammatory responses and increasing asymmetric dimethylarginine:arginine (ADMA:arginine), a biomarker that is predictive of reduced NO biosynthesis. In a randomized, cross-over design, healthy men (n = 16; 21.6 ± 0.8 y) ingested glucose or fructose (75 g) after an overnight fast. Brachial artery flow-mediated dilation (FMD), plasma glucose and insulin, antioxidants, malondialdehyde (MDA), inflammatory proteins, arginine, and ADMA were measured at regular intervals during the 3-h postprandial period. Baseline FMD did not differ between trials (P > 0.05). Postprandial FMD was reduced following the ingestion of glucose only. Postprandial MDA concentrations increased to a greater extent following the ingestion of glucose compared to fructose. Plasma arginine decreased and the ratio of ADMA:arginine increased to a greater extent following the ingestion of glucose. Inflammatory cytokines and cellular adhesion molecules were unaffected by the ingestion of either sugar. Postprandial AUC(0-3 h) for FMD and MDA were inversely related (r = -0.80; P < 0.05), suggesting that hyperglycemia-induced lipid peroxidation suppresses postprandial vascular function. Collectively, these findings suggest that postprandial hyperglycemia in healthy men reduces endothelium-dependent vasodilation by increasing lipid peroxidation independent of inflammation. Postprandial alterations in arginine and ADMA:arginine also suggest that acute hyperglycemia may induce VED by decreasing NO bioavailability through an oxidative stress-dependent mechanism. Additional work is warranted to define whether inhibiting lipid peroxidation and restoring arginine metabolism would mitigate hyperglycemia-mediated decreases in vascular function.
Journal of Nutrition 09/2011; 141(11):1961-8. · 3.92 Impact Factor
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ABSTRACT: Regulatory T cells (Treg) are critical in maintaining immune tolerance and suppressing autoimmunity. The transcription factor Foxp3 serves as a master switch that controls the development and function of Treg. Foxp3 expression is epigenetically regulated by DNA methylation, and DNA methyltransferase (DNMT) inhibitors can induce Foxp3 expression in naive CD4(+) T cells. We showed that EGCG, a major green tea polyphenol, could act as a dietary DNMT inhibitor, and induced Foxp3 and IL-10 expression in CD4(+) Jurkat T cells at physiologically relevant concentrations in vitro. We further showed that mice treated with EGCG in vivo had significantly increased Treg frequencies and numbers in spleen and lymph nodes and had inhibited T cell response. Induction of Foxp3 expression correlated with a concomitant reduction in DNMT expression and a decrease in global DNA methylation. Our data suggested that EGCG can induce Foxp3 expression and increase Treg frequency via a novel epigenetic mechanism. While the DNMT inhibitory effects of EGCG was not as potent as pharmacologic agents such as 5-aza-2'-deoxycytidine, the ability of dietary agents to target similar mechanisms offers opportunities for potentially sustained and longer-term exposures with lower toxicity. Our work provides the foundation for future studies to further examine and evaluate dietary strategies to modulate immune function.
Immunology letters 05/2011; 139(1-2):7-13. · 2.91 Impact Factor
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ABSTRACT: Animal and epidemiological studies suggest that green tea catechins may reduce the risk of cardiovascular diseases [e.g., coronary heart disease (CHD)]. The health benefit of green tea has been attributed to its antioxidant and anti-inflammatory properties; however, considerable evidence suggests that green tea and its catechins may reduce the risk of CHD by lowering the plasma levels of cholesterol and triglyceride. Although the mechanism underlying such effect of green tea is yet to be determined, it is evident from in vitro and in vivo studies that green tea or catechins inhibit the intestinal absorption of dietary lipids. Studies in vitro indicate that green tea catechins, particularly (-)-epigallocatechin gallate, interfere with the emulsification, digestion, and micellar solubilization of lipids, critical steps involved in the intestinal absorption of dietary fat, cholesterol, and other lipids. Based on the observations, it is likely that green tea or its catechins lower the absorption and tissue accumulation of other lipophilic organic compounds. The available information strongly suggests that green tea or its catechins may be used as safe and effective lipid-lowering therapeutic agents.
The Journal of Nutritional Biochemistry 04/2007; 18(3):179-83. · 3.89 Impact Factor
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ABSTRACT: We conducted this study to determine whether green tea constituents, (-)-epigallocatechin gallate (EGCG) and caffeine, affect the intestinal absorption of cholesterol (CH), fat, and other fat-soluble compounds. Ovariectomized rats with lymph cannula were infused intraduodenally with a lipid emulsion containing 14C-labeled CH (14C-CH), alpha-tocopherol (alpha TOH), triolein, and sodium taurocholate, without (control) or with EGCG, caffeine, or EGCG plus caffeine, in PBS, pH 6.5. The lymphatic total 14C-CH was significantly lowered by EGCG (21.1 +/- 2.1% dose), caffeine (27.9 +/- 1.7% dose), and EGCG plus caffeine (19.3 +/- 0.9% dose), compared with the control (32.4 +/- 1.6% dose). The lymphatic output of esterified CH also was significantly lower in rats infused with EGCG (7.9 +/- 0.7 micromol), caffeine (7.6 +/- 0.2 micromol), and EGCG plus caffeine (7.5 +/- 0.6 micromol) than rats in the control group (11.6 +/- 1.7 micromol). Also, EGCG and caffeine significantly lowered the absorption of alpha TOH, another highly hydrophobic lipid. However, the lymphatic outputs of oleic acid (exogenous fatty acid marker) and other fatty acids of endogenous origin were not affected by EGCG but were markedly lowered by caffeine and EGCG plus caffeine. Caffeine significantly lowered the amount of lymph flow, regardless of whether it was infused alone (14.2 +/- 3.9 mL) or with EGCG (18.6 +/- 2.0 mL), compared with EGCG (22.2 +/- 2.2 mL) alone and the control group (23.2 +/- 3.8 mL). The caffeine-induced decline in lymph flow was associated with the lowering of lipid absorption. The results indicate that both EGCG and caffeine inhibit lipid absorption and that the inhibitory effects of the 2 tea constituents are not synergistic but mediated by distinctly different mechanisms.
Journal of Nutrition 12/2006; 136(11):2791-6. · 3.92 Impact Factor
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ABSTRACT: This study was conducted to examine whether the inhibition of intestinal lipid absorption by green tea is associated with the inhibitory effect of its catechins on pancreatic phospholipase A(2) (PLA(2)). PLA(2) activity was assayed by using 1,2-dioleoylphosphatidylcholine (DOPC), porcine pancreatic PLA(2) and catechins at varying concentrations (0.075-1.80 micromol/L). The amount of 1-oleoyl-2-hydroxyphosphatidylcholine liberated was determined by HPLC. The percentage of inhibition of PLA(2) by catechins at 0.6 micromol increased in the order of (-)-epicatechin (23.3%), (+)-catechin (CAT; 24.8%), (-)-epigallocatechin (25.7%), (-)-epicatechin gallate (39.7%) and (-)-epigallocatechin gallate (EGCG; 64.9%). In an in vivo study, ovariectomized rats with lymph cannula were infused intraduodenally for 8 h with a triolein emulsion containing [dioleoyl-1-(14)C]-phosphatidylcholine, DOPC, alpha-tocopherol (alphaTOH) and retinol (ROH) without (CAT0) or with CAT or EGCG. The lymphatic total (14)C-radioactivity was significantly lowered by EGCG (45.5+/-4.9% dose) compared with CAT (56.2+/-5.2% dose) and CAT0 (64.7+/-2.0% dose). The (14)C-radioactivity remaining in the small intestinal lumen and cecum was higher in EGCG (24.1% dose) than in CAT (9.5% dose) and CAT0 rats (9.0% dose). Significantly less (14)C radioactivity was incorporated into lymph triacylglycerol and cholesteryl ester in EGCG rats. The absorption of alphaTOH, used as a marker of extremely hydrophobic lipids, was significantly lower in EGCG (7.8+/-1.7 micromol) than in CAT (14.4+/-2.8 micromol) and CAT0 rats (16.8+/-2.1 micromol). The absorption of ROH was unaffected, whereas oleic acid output was lower in EGCG rats. The results show that EGCG inhibits the intestinal absorption of lipids, which is in part associated with its inhibition of phosphatidylcholine hydrolysis. Data suggest that EGCG may inhibit the absorption of other highly lipophilic organic compounds.
The Journal of Nutritional Biochemistry 08/2006; 17(7):492-8. · 3.89 Impact Factor
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ABSTRACT: This study was conducted to determine whether the feeding of dietary L-carnitine (CN) improves the intestinal absorption of fat and alpha-tocopherol (alphaTOH) in ovariectomized (OX) rats. OX adult rats were weight-matched and assigned to 2 groups fed a modified AIN-93G diet containing alphaTOH-stripped soybean oil without (-CN) or with (+CN) supplemental CN at 150 mg/kg diet. At 5 wk, each rat with a lymph cannula was infused intraduodenally at 3.0 mL/h with a lipid emulsion consisting of 565 micromol triolein labeled with (14)C ((14)C-OA), 3.6 micromol alphaTOH, and 396 micromol sodium taurocholate in 24 mL PBS buffer. Lymph was collected hourly for 8 h and analyzed for lipids. The lymphatic absorption of alphaTOH for 8 h in +CN rats (899 +/- 201 nmol) was higher (P < 0.05) than in -CN rats (587 +/- 92 nmol). The absorption of (14)C-OA in +CN rats (53.5 +/- 4.0% dose/8 h) also was increased (P < 0.05) compared with -CN rats (47.6 +/- 5.0% dose/8 h). Lymph flow did not differ between the groups. When bile was diverted but with infusion of sodium taurocholate, the lymphatic absorption of lipids did not differ. The present study provides evidence that dietary CN enhances the rates and amounts of lymphatic absorption of alphaTOH and fat in OX rats. Our findings suggest that dietary CN may influence the process of lipid packaging and absorption by the enterocyte in OX rats, and may explain in part the increased status of alphaTOH in CN-fed animals.
Journal of Nutrition 04/2005; 135(4):753-6. · 3.92 Impact Factor
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ABSTRACT: We reported previously that egg sphingomyelin (SM) inhibits the intestinal absorption of cholesterol and fat in rats. This study was conducted to compare the relative efficiencies of milk and egg SM in inhibiting intestinal absorption of cholesterol and other lipids. Adult male rats with lymph cannulae were infused at 3.0 mL/h for 8 h via a duodenal catheter with a lipid emulsion (451.7 micromol triolein, 20.7 micromol cholesterol, 33.3 kBq (14)C-cholesterol, 3.1 micromol alpha-tocopherol, and 396.0 micromol sodium taurocholate in 24 mL PBS, pH, 6.5), without SM (controls), or with 80.0 micromol egg SM or milk SM. The lymphatic absorptions of (14)C-cholesterol were significantly lower in rats infused with milk SM (19.5 +/- 1.4% dose) and egg SM (24.4 +/- 1.9% dose) than in those infused with no SM (37.6 +/- 1.8% dose). In addition, the lymphatic outputs of fatty acids and phospholipid were significantly lowered by milk and egg SM. Similarly, the absorption of alpha-tocopherol also was decreased by milk SM (13.6 +/- 1.7% dose) and egg SM (18.3 +/- 2.4% dose) compared with controls (27.0 +/- 1.8% dose). Total lymphatic SM output was not affected by egg SM, but markedly decreased by milk SM, relative to controls. The results indicate that both milk and egg SM markedly inhibit the absorption of cholesterol, fat, and other lipids. However, milk SM is a more potent inhibitor than egg SM. The strong inhibitory effect of milk SM may be associated with the higher degree of saturation and longer chain length of its fatty acyl groups, which may slow the rate of luminal lipolysis, micellar solubilization, and transfer of micellar lipids to the enterocyte.
Journal of Nutrition 11/2004; 134(10):2611-6. · 3.92 Impact Factor
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Duy H Hua,
Xiaodong Huang,
Yi Chen,
Srinivas K Battina,
Masafumi Tamura, Sang K Noh,
Sung I Koo,
Ichiji Namatame,
Hiroshi Tomoda,
Elisabeth M Perchellet,
Jean-Pierre Perchellet
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ABSTRACT: Tetracyclic pyrans (+)-chloropuupehenone (1) and (+)-chloropuupehenol (5) and its C8-R-isomer (+)-3 were synthesized via a one-pot condensation of 1-chloro-2-lithio-3,5,6-tris(tert-butyldimethylsilyloxy)benzene (8) with (4aS,8aS)-3,4,4a,5,6,7,8,8a-octahydro-2,5,5,8a-tetramethylnaphthalene-1-carboxaldehyde (7). The major condensation product, (4aS,6aR,12bS)-2H-9,10-bis(tert-butyldimethylsilyloxy)-11-chloro-1,3,4,4a,5,6,6a,12b-octahydro-4,4,6a,12b-tetramethyl-benzo[a]xanthene (4), after desilylation provided tetracyclic pyran (+)-(4aS,6aR,12bS)-2H-11-chloro-1,3,4,4a,5,6,6a,12b-octahydro-4,4,6a,12b-tetramethyl-benzo[a]xanthene-9,10-diol (3). At a dosage of 42 mg/rat over 8 h, pyran diol 3 inhibited the intestinal absorption of cholesterol by 71% in rats. Tetracyclic pyran 4 was also converted to o-quinone 28, which inhibited cholesteryl ester transfer protein (CETP) activity and L1210 leukemic cell viability with IC(50) values of 31 and 2.4 microM, respectively. Diol (+)-5 inhibited CETP activity with an IC(50) value of 16 microM. The minor condensation product, (4aS,6aS,12bS)-2H-9,10-bis(tert-butyldimethylsilyloxy)-11-chloro-1,3,4,4a,5,6,6a,12b-octahydro-4,4,6a,12b-tetramethyl-benzo[a]xanthene (6), was transformed into (+)-5 and (+)-1. A stepwise stereoselective synthesis of (+)-1 was also developed utilizing an oxyselenylation ring-closure reaction. The synthetic sequence also produced four biologically active naturally occurring drimanic sesquiterpenes, (+)-drimane-8alpha,11-diol (34), (-)-drimenol (38), (+)-albicanol (39), and (-)-albicanal (31) as intermediates.
The Journal of Organic Chemistry 10/2004; 69(18):6065-78. · 4.45 Impact Factor
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ABSTRACT: Evidence indicates that phosphatidylcholine (PC) inhibits the intestinal absorption of cholesterol (CH) in rats. This study was designed to determine whether sphingomyelin (SM), structurally similar to PC, also inhibits the lymphatic absorption of CH. Sprague-Dawley rats with lymph cannulae were infused at 3.0 mL/h for 8 h via a duodenal catheter with a lipid emulsion [33.3 kBq 14C-CH, 20.7 micromol CH, 451.7 micromol triolein, 3.1 micromol alpha-tocopherol (alphaTP), 75.4 nmol retinol and 396.0 micromol sodium taurocholate in 24 mL of PBS (pH, 6.5)], without egg SM (SM0) as control, or with 5.0 micromol/h (SM5) or 10.0 micromol/h (SM10). Egg SM lowered the lymphatic absorption of 14C-CH in a dose dependent manner. Likewise, SM lowered the lymphatic absorptions of alphaTP and fatty acid (oleic acid), whereas it had no effect on retinol absorption. SM at a high dose (SM10) lowered the lymphatic outputs of both PC and SM, whereas there was no such effect at a lower dose (SM5). These results indicate that luminal egg SM has an inhibitory effect on the intestinal absorption of CH and other lipids of relatively high hydrophobicity. Our findings suggest that SM, if ingested in sufficient amounts, may inhibit the intestinal absorption of dietary lipids including cholesterol and alphaTP.
Journal of Nutrition 12/2003; 133(11):3571-6. · 3.92 Impact Factor
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ABSTRACT: Previously, we have shown that the lymphatic absorption of retinol is significantly decreased in rats fed a low zinc diet. This study was conducted to determine whether the absorption of beta-carotene also is altered in zinc-deficient male rats. The absorption of beta-carotene was estimated by determining the amount of retinol appearing in the mesenteric lymph during intraduodenal infusion of beta-carotene. One group of rats was fed the AIN-93G diet but low in zinc (LZ; 3 mg/kg) and the other was fed the same diet adequate in zinc (AZ; 30 mg/kg). The LZ and AZ rats were trained to meal feed equal amounts of the diets twice daily. At 6 weeks, each rat with lymph cannula was infused via an intraduodenal catheter at 3 ml/h for 8 h with a lipid emulsion containing 65.0 nM beta-carotene, 565.1 microM triolein, 27.8 kBq 14C-triolein (14C-OA), 72 mg albumin, and 396 microM Na-taurocholate in 24 ml PBS (pH 6.7). The lymphatic output of retinol over the 8-h period was significantly lower in LZ rats than in AZ rats. The absorption of 14C-OA also was significantly lower in LZ rats. No significant differences were observed between groups in intestinal beta-carotene 15,15'-dioxygenase, retinal reductase, and retinal oxidase activities. The findings demonstrate that low zinc intake or marginal zinc deficiency significantly lowers the absorption of beta-carotene as estimated by lymphatic retinol output. The results also indicate that the decrease in retinol output in LZ rats is not linked to defects in beta-carotene cleavage and subsequent conversion of retinal to retinol in the intestinal mucosa. This study suggests that zinc status is an important factor determining the intestinal absorption of beta-carotene and hence the nutritional status of vitamin A.
The Journal of Nutritional Biochemistry 04/2003; 14(3):147-53. · 3.89 Impact Factor
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ABSTRACT: Evidence indicates that green tea consumption lowers the serum level of cholesterol (CH). This study was conducted to determine whether green tea lowers the intestinal absorption of CH and other lipids in ovariectomized (OX) rats. OX rats with lymph duct cannulae were infused at 3.0 mL/h for 8 h via an intraduodenal catheter with a lipid emulsion containing (14)C-cholesterol ((14)C-CH) and alpha-tocopherol (alphaTP) without (GT0) or with green tea extract standardized to 42.9 mg (GT1) or 120.5 mg (GT2) of total catechins in PBS (pH 6.5). Green tea extracts dose-dependently reduced (P < 0.05) the lymphatic absorption of (14)C-CH. The cumulative absorptions of (14)C-CH in rats infused with GT0, GT1 and GT2 were 36.3 +/- 1.1, 20.7 +/- 4.3 and 4.8 +/- 4.1% dose, respectively. The percentage distribution of esterified CH did not differ between rats infused with GT0 and GT1 (80.2 +/- 2.3% vs. 79.0 +/- 1.7%), but was significantly lower in those given GT2 (69.1 +/- 6.8%). The absorption of alphaTP also was significantly reduced by GT1 (736.5 +/- 204.9 nmol, 20.8 +/- 5.8% dose) and GT2 (281.0 +/- 190.8 nmol, 7.9 +/- 5.4% dose) compared with GT0 (1048.8 +/- 174.9 nmol, 29.6 +/- 4.9% dose). The absorption of fat was significantly increased by GT1 (862.6 +/- 151.1 micromol) but lowered by GT2 (557.9 +/- 252.2 micromol) relative to GT0 (717.7 +/- 39.1 micromol). The findings provide direct evidence that green tea has a profound inhibitory effect on the intestinal absorption of CH and alphaTP in OX rats. Whether the inhibitory effect of green tea extract is attributable to a specific catechin(s) and other components in green tea remains to be determined.
Journal of Nutrition 06/2002; 132(6):1282-8. · 3.92 Impact Factor
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ABSTRACT: Previous work has shown that a low dietary intake of zinc for a short duration significantly lowers the lymphatic absorption
of α-tocopherol (αTP) in adult male rats. The present study investigated whether the nutritional status of zinc is critical
in maintaining the tissue levels of the vitamin. One group of rats was fed an AIN-93G diet containing 3 mg zinc/kg (low zinc,
LZ) and the other was fed the same diet but containing 30 mg zinc/kg (adequate zinc, AZ). Food intakes between groups were
matched by feeding two meals per day. At 6 wk, the body weights (356±8 g) of LZ rats reached 98% those (362±10 g) of AZ rats.
Feeding of the LZ diet for 6 wk significantly lowered the concentrations of both αTP and zinc in the liver, kidney, heart,
testis, and brain. No consistent relationships between αTP and zinc concentrations were observed in other tissues such as
spleen, lung, gastrocnemius muscle, and retroperitoneal fat tissues. The concentrations of αTP in the liver, testis, brain,
spleen, heart, and kidney were significantly correlated with the tissue concentrations of zinc. The LZ diet slightly but significantly
increased the total lipid contents (mg/g) of liver, kidney, heart, and spleen. However, the tissue levels of phospholipid
(µmol/100 mg lipid) in the heart, lung, testis, and spleen were decreased significantly in LZ rats. These findings indicate
that low zinc intake results in a pronounced decrease in the animal’s αTP status under the conditions of matched food intakes,
body weights, and feeding patterns. The lower tissue levels of αTP may explain in part the compromised antioxidant defense
system and increased susceptibility to oxidative damage observed in zinc deficiency.
Biological Trace Element Research 01/2001; 81(2):153-168. · 1.92 Impact Factor
