慢性阻塞性肺疾病一氧化氮、肿瘤坏死因子和白细胞介素6研究

目的 了解慢性阻塞性肺疾病（ＣＯＰＤ）患者一氧化氮（ＮＯ）和肿瘤坏死因子（ＴＮＦα）、白细胞介素６（ＩＬ－６）的相互关系,探讨它们在发病中的作用。方法 测定ＣＯＰＤ急性加重期患者３２例,稳定期患者２８例及健康人１０例血清ＮＯ＾－２、ＴＮＦα、ＩＬ－６水平。ＮＯ＾－２测定用萘乙烯二胺盐酸盐比色法,ＴＮＦα、ＩＬ－６测定用ＥＬＩＳＡ法。结果：ＣＯＰＤ急性期患者血清ＮＯ＾－２、ＴＮＦα、ＩＬ－６均显著高     

妇科肿瘤患者血清中细胞因子的表达及意义

目的：研究妇科肿瘤患者血清中细胞因子的变化，探索与发病机理的相关性。方法：以双抗体夹心ＥＬＩＳＡ法对７９例妇科肿瘤患者血清中肿瘤坏死因子（ＴＮＦ－α）、白细胞介素－６（ＩＬ－６）、白细胞介素－８（ＩＬ－８）和白细胞介素－１０（ＩＬ－１０）水平进行了监测。结果：妇科恶性肿瘤组ＴＮＦ－α、ＩＬ－６、ＩＬ－８和ＩＬ－１０水平均明显高于正常对照组和妇科良性肿瘤组（Ｐ＜０．０１），其中尤以卵巢癌增高最为明显，其次为子宫内膜癌和滋养细胞肿瘤。结论：说明ＴＮＦ－α、ＩＬ－６、ＩＬ－８和ＩＬ－１０细胞因子可能参与肿瘤的形成和发展过程，并对妇科良、恶性肿瘤的鉴别诊断有一定意义。     

慈菇对CCL4致大鼠肝纤维化NO及TNF—α影响的观察

采用５月龄Ｗｉｓｔａｒ大鼠,用ＣＣＬ４灌胃致大鼠形成肝组织纤维化,并试以慈菇作为ＣＣＬ４致大鼠肝纤维化过程的干预因素的实验。结果显示：在肝纤维化发生的同时,血清ＮＯ、ＴＮＦ－α显著增多,腹腔巨噬细胞诱生的ＮＯ、ＴＮＦ－α也明显增多;在实验的第８～１２周,灌饲慈菇汁的大鼠血清及腹腔巨噬细胞诱生的ＮＯ、ＴＮＦ－α水平均明显低于阳性对照组。提示ＮＯ和ＦＮＦ－α在肝纤维化过程中起重要作用,慈菇可减轻ＣＣＬ４致大鼠肝纤化程度并减少ＮＯ与ＴＮＦ－α的产生。     

桦木尘和柞木尘对大鼠肺泡巨噬细胞分泌细胞因子的影响

为研究体外桦木尘（ＢＤ）和柞木尘（ＯＤ）对大鼠肺泡巨噬细胞（ＡＭ）分泌细胞因子的影响，从支气管肺泡灌洗液中分离３０只Ｗｉｓｔａｒ大鼠的ＡＭ，进行体外培养，分别以不同剂量的ＢＤ或ＯＤ（１００、１５０、２００、２５０μｇ／ｍｌ）诱导ＡＭ，于不同时间（４、２４、４８、７２小时），检测ＡＭ分泌ＩＬ－１、ＩＬ－２、ＩＬ－６和ＴＮＦα的活性。结果显示：ＢＤ和ＯＤ诱导ＡＭ分泌ＩＬ－１、ＩＬ－２、ＩＬ－６和ＴＮＦα，其活性均高于或明显高于对照组（Ｐ＜０．０５或Ｐ＜０．０１），而ＢＤ组与ＯＤ组相比，也有不同或明显不同（Ｐ＜０．０５或Ｐ＜０．０１）。在２００μｇ／ｍｌ的时间曲线中也显示ＢＤ组高于或明显高于ＯＤ组（Ｐ＜０．０５或Ｐ＜０．０１）。提示：ＢＤ和ＯＤ均能刺激ＡＭ分泌ＩＬ－１、ＩＬ－２、ＩＬ－６和ＴＮＦα的活性增加，而ＢＤ较ＯＤ更为明显。     

透析液污染对血透患者细胞因子和淋巴细胞亚群的影响

目的探讨透析液污染与血液透析患者外周血白细胞介素１（ＩＬ－１）、白细胞介素６（ＩＬ－６）、肿瘤坏死因子α（ＴＮＦα）及淋巴细胞亚群ＣＤ４、ＣＤ８的关系。方法使用同一批次生产的浓缩透析液分别于配制当天,存贮２、４、８、１２周后用于血透并作透析液细菌培养,同期检测患者透析前后外周血ＩＬ－１、ＩＬ－６、ＴＮＦα及淋巴细胞亚群ＣＤ４、ＣＤ８的变化。结果透析液存贮８周后透析液细菌培养菌落数目较新鲜配制时有极显著增加（Ｐ＜０．０１）;存贮８周后透析液用于血透患者,透析后ＩＬ－１、ＴＮＦα水平较透析前显著增加（Ｐ＜０．０５）;ＩＬ－６水平较透析前极显著增加（Ｐ＜０．０１）;淋巴细胞亚群ＣＤ４较透析前增加（Ｐ＜０．０５）、ＣＤ８变化不明显（Ｐ＞０．０５）。结论透析液污染能促进血透患者单核细胞释放ＩＬ－１、ＴＮＦα,诱导ＩＬ－６产生增加,是引起透析并发症的重要原因之一。     

新生儿败血症血清IL06和TNF—α的检测

为探讨白细胞介素－６（ＩＬ－６）和肿瘤坏死因子－α（ＴＮＦ－α）在新生儿败血症中的变化，采用双抗体夹心ＥＬＩＳＡ法对３０例新生儿败血症患儿血清ＩＬ－６和ＴＮＦ－α水平进行检测。结果表明新生儿败血症患儿血清ＩＬ－６和ＴＮＦ－α水平显著高于对照组，且ＩＬ－６和ＴＮＦ－α之间存在正相关关系。     

维生素A及维生素C对肺巨噬细胞产生活性氧及细胞因子的影响

目的 为观察维生素Ａ（ＶＡ）及维生素Ｃ（ＶＣ）对肺巨噬细胞（肺Ｍφ）功能的影响。方法 以大鼠 动物模型观察ＶＡ及ＶＣ对大鼠肺Ｍφ产生自由基（Ｏ２，Ｈ２Ｏ２）及细胞因子（ＩＬ－１，ＴＮＦ－α）的影响。结果 补充ＶＡ及ＶＣ均明显增加肺Ｍφ的吴噬功能及Ｏ２、Ｈ２Ｏ２的产生；补充ＶＡ可明显增加细胞因子（ＩＬ０－１，ＴＮＦα）的产生，而补充ＶＣ效果不明显。结论适当补充ＶＡ可活化肺Ｍφ的吞噬功能及Ｏ２、Ｈ２Ｏ     

胃癌患者血清sIL-2R和TNF-α水平的临床观察

应用酶联免疫双抗夹心法对７８例胃癌患者血清可溶性白介素２－受体（ｓＩＬ－２Ｒ）和肿瘤坏死因子－α（ＴＮＦ－α）进行临床观察。结果发现：胃癌患者血清ｓＩＬ－２Ｒ和ＴＮＦ－α水平明显高于胃良性疾病和正常人（Ｐ＜０．０１）；Ⅲ、Ⅳ期高于Ⅰ、Ⅱ期（Ｐ＜０．０１）；手术切除后（根治性或姑息性）ｓＩＬ－２Ｒ和ＴＮＦ－α显著下降（Ｐ＜０．０１）；手术后复发或转移患者血清中ｓＩＬ－２Ｒ和ＴＮＦ－α含量升高（Ｐ＜０．０１）；ｓＩＬ－２Ｒ和ＴＮＦ－α水平呈正相关（ｒ＝０．３３）；如果患者血清ｓＩＬ－２Ｒ含量高于１０００ｕ／Ｌ同时伴有ＴＮＦ－α持续高于１２０ｎｇ／ｍｌ，预兆生存期短。监测胃癌患者血清ｓＩＬ－２Ｒ和ＴＮＦ－α水平对临床诊断，病情估计和预后有重大意义。     

乙型病毒性肝炎患者血清TNF-α、IFN-γ、IL-6和IL-8的检测及意义

采用双抗体夹心ＥＬＩＳＡ法对６６例乙型肝炎和２０例健康献血员血清ＴＮＦ－α、ＩＦＮ－γ、ＩＬ－６和ＩＬ－８进行检测。结果显示：各临床型乙型肝炎血清ＴＮＦ－α、ＩＬ－６水平均明显高于健康献血员（Ｐ＜０．０５），除急性肝炎外，其它型肝炎血清ＩＦＮ－γ、ＩＬ－８水平亦明显高于健康对照组（Ｐ＜０．０５）；重型肝炎组升高更为明显，与急性肝炎组比较，ＴＮＦ－α、ＩＦＮ－γ、ＩＬ－６、ＩＬ－８水平前者明显高于后者，差异显著（Ｐ＜０．０５）；各型乙型肝炎患者ＴＮＦ－α与ＩＦＮ－γ、ＩＬ－６、ＩＬ－８呈正相关，相关系数ｒＩＦＮ＝０．２４，Ｐ＜０．０５，ｒＩＬ－６＝０．３５、Ｐ＜０．０５，ｒＩＬ－８＝０．４４、（Ｐ＜０．０５）；ＴＮＦ－α、ＩＦＮ－γ、ＩＬ－６、ＩＬ－８与血清总胆红素（ＴＢｉＬ）呈正相关（Ｐ＜０．０５）；动态观察急性肝炎和重型肝炎病程中诸因子的变化，发现ＩＦＮ－γ在病程初和肝昏迷开始时水平最高，而ＴＮＦ－α、ＩＬ－６、ＩＬ－８随病情加重而逐渐上升，肝损伤最重时达高峰，随病情好转逐渐下降。结果提示：细胞因子异常增高与肝脏炎症有关，可能是通过各种途径共同导致肝细胞损伤。     

细胞因子在睾丸局部调节中的作用

睾丸中巨噬细胞分泌大量ＩＬ－１，间质细胞上有ＩＬ－１ｍＲＮＡ表达，ＩＬ－１通过自分泌或旁分泌影响间质细胞睾酮生物合成。睾丸中支持细胞分泌ＩＬ－１类似因子和ＩＬ－６，调节生精过程。睾丸中ＴＮＦα通过影响ＦＳＨ对支持细胞的刺激作用和对间质细胞睾酮的生物合成，也影响生精过程。此领域的深入研究有助于阐明睾丸内各细胞成分的相互作用及其分泌细胞因子在整个睾丸生命周期中的作用。     

Erythrocyte copper chaperone for superoxide dismutase is increased following marginal copper deficiency in adult and postweanling mice

A sensitive and reliable biomarker has yet to be identified for marginal copper deficiency in humans. The need for such a biomarker is critical, because increased cases of human copper deficiency evolve following bariatric surgery and other secondary factors besides diet. Four experiments were devised to induce marginal copper deficiency through copper-deficient (CuD) diets (5 wk for mice and 4 wk for rats). In Expt. 1 and 2, male postweanling mice were raised in either solid-bottom plastic cages (Expt. 1) or stainless steel hanging cages (Expt. 2) and compared. Postweanling rats (Expt. 3) and adult mice (Expt. 4) were also studied using stainless steel cages. Copper-adequate controls were fed a semipurified diet containing 9 mg Cu/kg. CuD rats exhibited the most severe changes in biomarkers due to copper limitation, including major reductions in plasma ceruloplasmin (Cp) and erythrocyte superoxide dismutase (Sod1) and augmentation in copper chaperone for Sod1 (CCS). The CuD mice in Expt. 2 were more deficient than the CuD mice in Expt. 1, likely due to coprophagia differences. In fact, the CuD mice in Expt. 1 had unaltered Sod1 or Cp levels. Importantly though, these marginally deficient mice and CuD adult mice that had no changes in Cp activity or liver copper level had robust augmentation of CCS. Erythrocyte CCS was the only consistent biomarker to change in copper deficiency for all dietary groups, suggesting that CCS may be an excellent biomarker for human confirmation of marginal copper deficiency.     

Regression of dietary copper restriction-induced cardiomyopathy by copper repletion in mice

Dietary copper deficiency (CuD)(3) leads to cardiac hypertrophy in various animal models. We showed recently that heart failure develops after hypertrophy in FVB mice fed a CuD diet. The present study was undertaken to determine whether CuD-induced cardiac failure is reversible upon copper repletion (CuR). Dams of FVB mice were fed a CuD diet (0.3 mg/kg) starting from d 3 postdelivery; the weanling pups were fed the same diet until CuR with 6.0 mg/kg Cu in the diet at 4 or 5 wk of age. CuR at 4 wk of age prevented the body weight loss; at 5 wk of age, it resulted in the regaining of the lost weight caused by CuD. A significant regression of CuD-induced cardiac hypertrophy was observed in the CuR mice. Histopathological examination revealed that CuR eliminated CuD-caused lipid deposition in the myocardium, and electron microscopy demonstrated that CuD-induced ultrastructural changes such as mitochondrial swelling and organelle structural disarray were all reversed in the CuR mice. Hemodynamic analysis showed that the CuD-depressed systolic and diastolic parameters such as the maximal rate of left ventricular pressure rise (+dP/dt) and decline (-dP/dt), and the contraction and relaxation times were completely recovered in the CuR mice. Furthermore, the CuD-blunted myocardial responses to the beta-adrenergic agonist, isoproterenol, were also restored in the CuR mice. This study thus demonstrates for the first time that CuR results in the regression of heart failure induced by CuD as demonstrated by the reversal of depressed cardiac hemodynamic and contractile function and the restored responsiveness to beta-adrenergic stimulation.     

Respiratory burst and candidacidal activity of peritoneal macrophages are impaired in copper-deficient rats

To investigate the effect of dietary copper deficiency on the function of peritoneal macrophages, weaned male Lewis rats were pair-fed diets containing either adequate (7 mg/kg diet; +Cu) or deficient (0.7 mg/kg diet; -Cu) levels of copper for 5 wk. Cellular copper content and the activity of Cu, Zn superoxide dismutase were significantly lower in both resident and thioglycollate-elicited macrophages from -Cu rats than in cells from +Cu controls. Reduced cellular Cu status was associated with impaired respiratory burst as assessed by zymosan-induced chemiluminescent activity and superoxide anion (O2-) generation. Candidacidal activity of macrophages from -Cu rats was also reduced and was highly correlated with chemiluminescent activity and O2- generation. In contrast, phagocytosis of opsonized erythrocytes by peritoneal macrophages from -Cu rats was normal. Elicited peritoneal macrophages from marginally Cu-deficient rats also killed significantly fewer yeast cells than macrophages from +Cu rats. These results demonstrate that macrophage function is impaired by dietary Cu deficiency and that the candidacidal activity of these cells may provide a sensitive indicator of Cu status.     

Dietary copper deficiency reduces iron absorption and duodenal enterocyte hephaestin protein in male and female rats

The mechanism for reduced Fe absorption in Cu deficiency is unknown, but may involve the intestinal Cu-dependent ferroxidase, Hephaestin (Hp). A 2 x 2 factorial experiment was designed to include Cu-deficient (CuD) and Cu-adequate (CuA) male and female rats. Weanling rats of both sexes were randomly divided into 2 groups each and fed an AIN-93G diet with low (<0.3 mg/kg; CuD) or adequate Cu (5.0 mg/kg; CuA). After 19 d, rats were fed 1.0 g each of their respective diets labeled with (59)Fe. Retained (59)Fe was monitored by whole-body counting for 12 d. Then, rats were killed for (59)Fe and Fe measurements in blood and various organs. Duodenal enterocytes were isolated for Western blot analysis of Hp. Signs of Cu and Fe deficiency were evident in both sexes. CuD male rats absorbed 60% as much Fe as CuA male rats (P < 0.001), whereas CuD female rats absorbed 70% (P < 0.001) as much as CuA females, with no difference between the sexes. Hp protein in enterocytes of CuD rats of both sexes was only 35% of that in CuA rats. The biological half-life of (59)Fe in CuD rats was only 50% (P < 0.001) of that in CuA rats, suggesting that Fe turnover was faster in CuD rats than CuA rats. Serum, spleen, and kidney Fe were lower (P < 0.001) in CuD rats than in CuA rats. Duodenal mucosa and liver Fe were higher (P < 0.01) in CuD male rats than CuA rats. Duodenal Fe but not liver Fe was higher in CuD female rats than CuA rats. Liver Fe was much higher (<0.001) overall in females than males. The data suggest that Cu deficiency reduces Fe absorption in rats through reduced expression of duodenal Hp protein.     

Pro-inflammatory HDL in women with obesity and nonalcoholic steatohepatitis

BackgroundIndividuals with non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH), are at increased risk for cardiovascular events, independent of traditional risk factors. Limited data on pro-inflammatory high density lipoprotein (HDL) in NASH exists in the literature. We hypothesized that HDL from individuals with NASH would be more pro-inflammatory than HDL from individuals without NASH.MethodsStudy participants were individuals with obesity who had undergone bariatric surgery with wedge liver biopsy. Using HDL isolated from serum obtained from study participants at the time of surgery, HDL-elicited macrophage cytokine expression (TNF-α, IL-1β, and IL-6) from THP-1 macrophages, HDL-associated receptor expression (ABCA1 and ABCG1) from apolipoprotein E deficient (apo E^−/−) mouse peritoneal macrophages, and isolevuglandin (isoLG) modified HDL were measured.Results11 women with NASH and 15 women without NASH were included in the study. Both TNF-α (P = 0.032) and IL-1β (P = 0.029) were significantly more expressed by THP-1 macrophages exposed to HDL from women with NASH compared to women without NASH. ABCA1 and ABCG1 expression by apo E^−/− mouse peritoneal macrophages was not significantly different when exposed to HDL from either women with NASH or women without NASH. IsoLG-modified HDL isolated from the serum of women with NASH trended higher than women without NASH.ConclusionOur study suggests a more pro-inflammatory HDL in women with obesity and NASH compared to women with obesity and without NASH.     

Cardiac cytochrome C oxidase activity and contents of subunits 1 and 4 are altered in offspring by low prenatal copper intake by rat dams

It has been reported previously that the offspring of rat dams consuming low dietary copper (Cu) during pregnancy and lactation experience a deficiency in cardiac cytochrome c oxidase (CCO) characterized by reduced catalytic activity and mitochondrial and nuclear subunit content after postnatal d 10. The present study was undertaken to determine whether the cardiac CCO deficiency was caused directly by low postnatal Cu intake or whether it was a prenatal effect of low Cu intake by the dams that became manifest postnatally. Dams were fed either a Cu-adequate diet (6 mg Cu/kg) or Cu-deficient diet (1 mg Cu/kg) beginning 3 wk before conception and throughout gestation and lactation. One day following parturition, several litters from Cu-adequate dams were cross fostered to Cu-deficient dams and several litters from Cu-deficient dams were cross fostered to Cu-adequate dams. Litters that remained with their birth dams served as controls. CCO activity, the content of the mitochondrial-encoded CCO subunit 1 (COX1), and the content of the nuclear-encoded subunit COX4 in cardiac mitochondria were reduced in the 21-d-old offspring of Cu-deficient dams. COX1 content was normal in the 21-d-old cross-fostered offspring of Cu-deficient dams, but CCO activity and COX4 were reduced. Cross fostering the offspring of Cu-adequate dams to Cu-deficient dams did not significantly affect CCO activity, COX1 content, or COX4 content in cardiac mitochondria of 21-d-old offspring. These data indicate that low prenatal Cu intake by dams was the determinant of CCO activity in cardiac mitochondria of the 21-d-old offspring and may have led to the assembly of a less-than-fully active holoenzyme.     

Copper deficiency induces the upregulation of the copper chaperone for Cu/Zn superoxide dismutase in weanling male rats

The most commonly used indices for determining copper deficiency in humans are reduced serum/plasma copper concentration and decreased activity of ceruloplasmin and Cu/Zn superoxide dismutase (SOD1). However, these indicators are influenced by many factors unrelated to copper status and lack the sensitivity required to detect marginal deficiency, limiting their usefulness in many situations. In vivo, the insertion of copper into SOD1 is dependent on the copper chaperone for SOD1 (CCS). In this study, we explored the possibility that the expression level of CCS may reflect copper status and thus serve as a useful marker of copper nutriture. Weanling male Wistar rats were fed either a normal (5.3 mg Cu/kg diet), moderately deficient (0.84 mg Cu/kg diet) or deficient (0.34 mg Cu/kg diet) copper diet for 6 wk. Rats fed moderate and deficient diets showed differences (P < 0.05) in several hematological measurements, indicating varying degrees of copper deficiency in these groups. Copper-deficient rats had reduced (P < 0.05) liver and erythrocyte SOD1 activity and body weight. Western blot analysis revealed a dose-dependent increase (P < 0.05) in CCS expression in liver and erythrocytes of copper-deficient rats. We report CCS protein level as a novel marker for assessing copper status.     

白藜芦醇对脂多糖诱导小鼠腹腔巨噬细胞炎性因子生成的调控

目的探讨白藜芦醇(Res)对脂多糖(LPS)诱导小鼠腹腔巨噬细胞核因子-κB(NF-κB)活化及炎性细胞因子[肿瘤坏死因子(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)]基因表达的调节。方法分别用1mg/LLPS或25mmol/LRes+1mg/LLPS处理体外培养的小鼠巨噬细胞,采用电泳迁移率改变分析法(EMSA)检测细胞中NF-κB活性,逆转录-聚合酶链反应(RT-PCR)和酶联免疫吸附法(ELISA)检测细胞中TNF-α、IL-1β、IL-6mRNA和蛋白的表达。结果LPS组NF-κB活性和TNF-α、IL-1β、IL-6含量在刺激后6～12h明显高于正常对照组(P<0.001),而Res+LPS组NF-κB活性和TNF-α、IL-1β、IL-6含量均显著低于LPS组(P<0.005)。结论LPS可诱导巨噬细胞NF-κB活化,导致TNF-α、IL-1β、IL-6基因表达增强,而Res能抑制NF-κB活化而调节TNF-α、IL-1β、IL-6基因的表达。     

High-fat diet blunts activation of the nuclear factor-κB signaling pathway in lipopolysaccharide-stimulated peritoneal macrophages of Wistar rats

ObjectiveThe present study was designed to investigate the effect of a high-fat diet (HFD) on the inflammatory response of peritoneal macrophages.MethodsMale Wistar rats were fed a control diet (n = 12) or an HFD (n = 12) for 12 wk. After euthanasia, peritoneal macrophages were collected and stimulated (or not) with lipopolysaccharide (LPS). Results from the assays using peritoneal macrophages were analyzed with one-way analysis of variance or an equivalent non-parametric test. The level of significance adopted was 0.05.ResultsConsumption of the HFD was associated with significant increases in weight gain and fat depots (P < 0.05). Despite having no influence in systemic markers of inflammation, such as interleukin (IL)-6, tumor necrosis factor-α, and plasminogen activator inhibitor-1, the HFD intake significantly decreased insulin sensitivity, as evaluated by the homeostasis model assessment index (P < 0.05). A decreased production of IL-1β, IL-6, IL-10, and nitric oxide in response to the LPS stimulation was observed in peritoneal macrophages from the HFD group (P < 0.05). Also, in HFD-fed animals, LPS incubation did not increase IL-1β and IL-6 mRNA expression (P < 0.05). These effects were associated with an attenuation of IκB inhibitor kinase-β phosphorylation and nuclear factor-κB activation in response to LPS and with a failure to decrease IκB inhibitor-α expression (P < 0.05).ConclusionChronic consumption of an HFD decreased the LPS-induced inflammatory response of peritoneal macrophages, which was associated with a downregulation of the nuclear factor-κB signaling pathway.     

Dietary supplementation with t-butylhydroquinone reduces cardiac hypertrophy and anemia associated with copper deficiency in rats

The effect of dietary supplementation with the antioxidant, t-butylhydroquinone (TBHQ), on some of the cardiovascular consequences of copper deficiency was investigated. Rats were fed copper-deficient (CuD) diet containing 0.3 μg Cu/g of diet that were either nonsupplemented or supplemented with TBHQ (supplied in the dietary safflower oil at a concentration of 0.02%). Control rats were fed copper adequate (CuA) diet containing >5.0 μg Cu/g (CuA) that also were either nonsupplemented or supplemented with TBHQ. After five weeks, rats consuming CuD diet supplemented with TBHQ exihibited plasma copper concentrations, ceruloplasmin activities, and liver and heart copper concentrations that were significantly (P<0.05) lower than those of rats consuming either nonsupplemented or TBHQ supplemented CuA diet, but no different from those of rats consiming nonsupplemented CuD diet. However, rats consuming CuD diet supplemented with TBHQ had significantly (P<0.05) higher growth, hemoglobin concentrations, hematocrits, and red blood cell qistribution widths but lower heart weights than rats consuming nonsupplemented CuD diet. TBHQ supplementation had no effect on these variables in rats fed CuA diet. Thus, while TBHQ did not improve copper status, it did ameliorate the growth reduction, anemia, and cardiac hypertrophy associated with copper deficiency. These findings indirectly support the contention that oxidative damage contributes to the pathophysiological consequences of copper deficiency.