RESUMO
BACKGROUND AND AIMS: Hypercholesterolemia is a major risk factor for atherosclerosis and cardiovascular diseases. Although resistant to hypercholesterolemia, the mouse is a prominent model in cardiovascular research. To assess the contribution of bile acids to this protective phenotype, we explored the impact of a 2-week-long dietary cholesterol overload on cholesterol and bile acid metabolism in mice. METHODS: Bile acid, oxysterol, and cholesterol metabolism and transport were assessed by quantitative real-time PCR, western blotting, GC-MS/MS, or enzymatic assays in the liver, the gut, the kidney, as well as in the feces, the blood, and the urine. RESULTS: Plasma triglycerides and cholesterol levels were unchanged in mice fed a cholesterol-rich diet that contained 100-fold more cholesterol than the standard diet. In the liver, oxysterol-mediated LXR activation stimulated the synthesis of bile acids and in particular increased the levels of hydrophilic muricholic acids, which in turn reduced FXR signaling, as assessed in vivo with Fxr reporter mice. Consequently, biliary and basolateral excretions of bile acids and cholesterol were increased, whereas portal uptake was reduced. Furthermore, we observed a reduction in intestinal and renal bile acid absorption. CONCLUSIONS: These coordinated events are mediated by increased muricholic acid levels which inhibit FXR signaling in favor of LXR and SREBP2 signaling to promote efficient fecal and urinary elimination of cholesterol and neo-synthesized bile acids. Therefore, our data suggest that enhancement of the hydrophilic bile acid pool following a cholesterol overload may contribute to the resistance to hypercholesterolemia in mice. This work paves the way for new therapeutic opportunities using hydrophilic bile acid supplementation to mitigate hypercholesterolemia.
Assuntos
Ácidos e Sais Biliares/metabolismo , Colesterol na Dieta/efeitos adversos , Ácidos Cólicos/uso terapêutico , Hipercolesterolemia/prevenção & controle , Animais , Colesterol na Dieta/metabolismo , Avaliação Pré-Clínica de Medicamentos , Hipercolesterolemia/etiologia , Masculino , Camundongos Endogâmicos C57BL , Receptores Citoplasmáticos e Nucleares/metabolismoRESUMO
Objective:TThe aim of this study is to investigate the effect of in vitro cultured Calculus Bovis on the inflammation of oropharynx and body in patients with OSA during the perioperative period of H-UPPP.Method:Eighty patients with OSA and H-UPPP indications were enrolled. The patients were divided into experimental group and control group by random number table, 40 cases in each group. The experimental group was given in vitro cultured Calculus Bovis, while the control group was not given bovine bezoar in vitro. The postoperative oropharyngeal pain, time to resume normal diet, local edema, concentration of IL-1ß, IL-8 and TNF-α in saliva, and concentration of IL-1ß, IL-8 and TNF-α in blood were compared between the two groups. Result:The pain of oropharynx in the experimental group was lighter than that in the control group on the 3rd, 5th and 7th day after operation (P<0.05), but there was no significant difference in the pain of oropharynx between the two groups on the 1st day after operation(P>0.05); the time of restoring normal diet in the experimental group was shorter than that in the control group (P<0.05); the edema of oropharynx in the experimental group was lighter than that in the control group on the 5th and 7th day after operation (P<0.05).The levels of IL-1ß, IL-8 and TNF-α in saliva were lower than those in control group on the 3rd, 5th and 7th day after operation (P<0.05), and the levels of IL-1ß, IL-8 and TNF-α in blood on the 5th and 7th day after operation were lower than those in control group (P<0.05).Conclusion:In vitro perioperative period of H-UPPP can improve the postoperative sore throat and local edema of oropharynx, shorten the time of normal diet and reduce the expression of related inflammatory factors in oropharynx and blood.
Assuntos
Ácidos Cólicos/uso terapêutico , Inflamação/prevenção & controle , Materia Medica/uso terapêutico , Orofaringe/patologia , Procedimentos Cirúrgicos Otorrinolaringológicos , Apneia Obstrutiva do Sono/cirurgia , Animais , Bovinos , Humanos , Interleucina-1beta/análise , Interleucina-8/análise , Período Pós-Operatório , Fator de Necrose Tumoral alfa/análiseRESUMO
The presence of lipopolysaccharide and emergence of drug resistance make the treatment of Gram-negative bacterial infections highly challenging. Herein, we present the synthesis and antibacterial activities of cholic acid-peptide conjugates (CAPs), demonstrating that valine-glycine dipeptide-derived CAP 3 is the most effective antimicrobial. Molecular dynamics simulations and structural analysis revealed that a precise intramolecular network of CAP 3 is maintained in the form of evolving edges, suggesting intramolecular connectivity. Further, we found high conformational rigidity in CAP 3 that confers maximum perturbations in bacterial membranes relative to other small molecules. Interestingly, CAP 3-coated catheters did not allow the formation of biofilms in mice, and treatment of wound infections with CAP 3 was able to clear the bacterial infection. Our results demonstrate that molecular conformation and internal connectivity are critical parameters to describe the antimicrobial nature of compounds, and the analysis presented here may serve as a general principle for the design of future antimicrobials.
Assuntos
Antibacterianos/uso terapêutico , Ácidos Cólicos/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Lipopolissacarídeos/metabolismo , Peptídeos/uso terapêutico , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/metabolismo , Animais , Antibacterianos/síntese química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Ácidos Cólicos/síntese química , Ácidos Cólicos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Escherichia coli/fisiologia , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Negativas/fisiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/metabolismo , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Conformação Molecular , Simulação de Dinâmica Molecular , Peptídeos/síntese química , Peptídeos/farmacologia , Relação Estrutura-AtividadeRESUMO
Nonalcoholic fatty liver disease is the most common cause of liver disease in the United States. There are no drug therapies approved for the treatment of nonalcoholic steatohepatitis (NASH). Multiple different pathways are involved in the pathogenesis and each can be the target of the therapy. It is possible that more than 1 target is involved in disease development and progression. Multiple clinical trials with promising agents are underway. Because NASH is a slowly progressive disease and treatment likely to be of prolonged duration, acceptance and approval of any agent will require information on long-term clinical benefits and safety.
Assuntos
Ácido Quenodesoxicólico/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Receptores Citoplasmáticos e Nucleares/agonistas , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antioxidantes/uso terapêutico , Inibidores de Caspase/uso terapêutico , Ácido Quenodesoxicólico/uso terapêutico , Ácidos Cólicos/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Incretinas/uso terapêutico , Resistência à Insulina , Liraglutida/uso terapêutico , Receptores X do Fígado/antagonistas & inibidores , Hepatopatia Gordurosa não Alcoólica/metabolismo , Pectinas/uso terapêutico , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Transportador 2 de Glucose-Sódio , Inibidores do Transportador 2 de Sódio-GlicoseRESUMO
AIM: The purpose of this work was to search for potential drugs with potent antitussive and expectorant activities as well as a low toxicity, but without addictive properties. Cholic acid-verticinone ester (CA-Ver) was synthesized based on the clearly elucidated antitussive and expectorant activities of verticinone in bulbs of Fritillaria and different bile acids in Snake Bile. In our previous study, CA-Ver showed a much more potent activity than codeine phosphate. This study was carried out to investigate the central antitussive mechanism and the addictive evaluation of CA-Ver. METHODS: Testing on a capsaicin-induced cough model of mice pretreated with naloxone, a non-selective opioid receptor antagonist, was performed for the observation of CA-Ver's central antitussive mechanism. We then took naloxone-induced withdrawal tests of mice for the judgment of CA-Ver's addiction. Lastly, we determined the opioid dependence of CA-Ver in the guinea pig ileum. RESULTS: The test on the capsaicin-induced cough model showed that naloxone could block the antitussive effect of CA-Ver, suggesting the antitussive mechanism of CA-Ver was related to the central opioid receptors. The naloxone-urged withdrawal tests of the mice showed that CA-Ver was not addictive, and the test of the opioid dependence in the guinea pig ileum showed that CA-Ver had no withdrawal response. CONCLUSION: These findings suggested that CA-Ver deserved attention for its potent antitussive effects related to the central opioid receptors, but without addiction, and had a good development perspective.
Assuntos
Antitussígenos , Tosse/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides , Receptores Opioides/agonistas , Animais , Antitussígenos/administração & dosagem , Antitussígenos/efeitos adversos , Antitussígenos/síntese química , Antitussígenos/farmacologia , Capsaicina , Cevanas/efeitos adversos , Cevanas/síntese química , Cevanas/uso terapêutico , Ácidos Cólicos/efeitos adversos , Ácidos Cólicos/síntese química , Ácidos Cólicos/uso terapêutico , Tosse/induzido quimicamente , Modelos Animais de Doenças , Interações Medicamentosas , Feminino , Cobaias , Íleo/efeitos dos fármacos , Técnicas In Vitro , Masculino , Camundongos , Naloxona/farmacologia , Síndrome de Abstinência a SubstânciasRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized countries. It has no accepted medical therapy. Fatty acid-bile acid conjugates (FABACs) were proven to prevent diet-induced NAFLD in rodents. AIM: This study was undertaken to test whether oral FABACs are also effective in reducing liver fat in preestablished diet-induced NAFLD. METHODS: NAFLD was induced in mice and rats by a high-fat diet and maintained by various proportions thereof. The FABACs used were conjugates of cholic acid with either arachidic or stearic acids. RESULTS: FABAC therapy reduced liver fat in all four series of experiments. The rapidity of the effect was inversely proportional to the concentration of fat in the maintenance diet. In mice on a 25% maintenance diet FABACs decreased total liver lipids by about 30% in 4 weeks (P<0.03). Diglycerides (P<0.003) and triglycerides (P<0.01) were the main neutral liver lipids that decreased during FABAC therapy. Both FABACs tested reduced liver fat in NAFLD at doses of 25 and 150 mg/kg/day. High-fat diet increased, whereas FABAC therapy decreased plasma 16 : 1/(16 : 0+16 : 1) fatty acid ratio - a marker of stearoyl CoA desaturase activity. In HepG2 cells FABACs decreased de-novo fatty acid synthesis dose dependently. CONCLUSION: Oral FABAC therapy decreased liver fat in preestablished NAFLD in mice and rats. Inhibition of stearoyl CoA desaturase activity and fatty acid synthesis are mechanisms that may contribute to this decrease. FABACs may be potential therapeutic agents for human NAFLD.
Assuntos
Ácidos e Sais Biliares/uso terapêutico , Gorduras na Dieta/efeitos adversos , Ácidos Graxos/uso terapêutico , Fígado Gorduroso/tratamento farmacológico , Animais , Glicemia/metabolismo , Ácidos Cólicos/uso terapêutico , Gorduras na Dieta/administração & dosagem , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Ácidos Graxos/biossíntese , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ratos , Ratos Endogâmicos F344 , Estearoil-CoA Dessaturase/sangue , Aumento de PesoRESUMO
OBJECTIVE: To estimate the therapeutic effect of single or combined use of jasminoidin and cholalic acid on focal cerebral ischemia rat with magnetic resonance-diffusion-weighted imaging (MR-DWI) technique, ultra-microscopy, and neuro-behavior scoring. METHODS: The model of cerebral ischemia-reperfusion injury was induced by string method. Three hours after reperfusion, MR-DWI was applied with ultra-microscopy and neuro-behavior test to give evaluation on cerebral ischemic rats, and pathologic, ultramicroscopic observation of tissue were taken as adjuvant measures to comprehensively evaluate the pharmacological effect on ischemia-reperfusion rats and delimit the efficacy of the two different components and their combination. RESULTS: Compared with the model group, ADC and DCavg values of the foci in all the treated groups had the incrensing trend. There was significant difference arund the foci in the group of combined use of jasminoidin and cholalic acid (P < 0.05). CONCLUSION: Combined use of jasminoidin and cholalic acid had protective effects on nerve and brain. MR-DWI technique accompanied with ultramicroscopic observation of tissues and neuro-behavior test is an effective method for evaluating the effect of neuro-protective agent.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Ácidos Cólicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Iridoides/uso terapêutico , Piranos/uso terapêutico , Animais , Imagem de Difusão por Ressonância Magnética/métodos , Quimioterapia Combinada , Gardenia/química , Masculino , Fármacos Neuroprotetores/uso terapêutico , Fitoterapia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controle , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
BACKGROUND: Fat malabsorption in the short-bowel syndrome (SBS) may in part be caused by decreased bile secretion. Cholylsarcosine is a synthetic conjugated bile acid resistant to bacterial degradation with no cathartic activity. METHODS: Metabolic balance studies were performed in four patients with SBS, two with a colon and two with a jejunostomy. RESULTS: Treatment with cholylsarcosine, 6 and 12 g/day, increased fat absorption by 17 +/- 3 g/day (0.7 MJ/day; P <0.05) and 20+/-1 g/day (0.8 MJ/day; P <0.001; mean +/- standard error), respectively, to a total absorption of energy from fat of 2.0-2.2 MJ/day. Total absorption of energy increased from 11.0 MJ/day to 11.7 MJ/day (bomb calorimetry). Energy absorbed from carbohydrates (6.5 MJ/day) did not change. Faecal output increased in one of the patients with a colon and was unchanged in the other three patients. A higher percentage of the medium-chain and the unsaturated fatty acids were absorbed in comparison with the long-chain and the saturated fatty acids (100% of C8:0, 92% of C10:0, 74% of C12:0, 52% of C14:0, 30% of C16:0, 16% of C18:0, and 47% of unsaturated C18 fatty acids). Treatment with cholylsarcosine increased absorption of C14:0 by 23%-29%, of C16:0 by 59%-74%, of C18:0 by 125%-138%, and of unsaturated C18-fatty acids by 36%-45%. A fifth patient (without a colon) was enrolled in the study but had to be excluded because cholylsarcosine, 6 g/day, resulted in nausea and anorexia. CONCLUSION: Cholylsarcosine increased fat absorption in SBS. The effect was relatively more pronounced on absorption of the low-absorbable, longer-chained, and saturated fatty acids. The overall gain in absorption of energy was small (6%) because energy absorption from carbohydrates was threefold higher than that from fat. Cholylsarcosine may have cathartic effects on some SBS patients with a colon. The maximal efficacy of cholylsarcosine was reached at a dose of 6 g/day, compared with 12 g/day in three of four patients.
Assuntos
Ácidos Cólicos/uso terapêutico , Sarcosina/análogos & derivados , Síndrome do Intestino Curto/tratamento farmacológico , Idoso , Análise de Variância , Calorimetria , Estudos Cross-Over , Gorduras na Dieta/análise , Ingestão de Energia , Metabolismo Energético , Gorduras/análise , Fezes/química , Feminino , Alimentos Formulados/análise , Humanos , Absorção Intestinal/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Sarcosina/uso terapêutico , Síndrome do Intestino Curto/fisiopatologiaRESUMO
We postulated that coadministration of cholylsarcosine with ursodeoxycholic acid might provide additional benefit to primary biliary cirrhosis patients with an incomplete response to ursodeoxycholic acid. Our aim was to test the tolerability and the effect of adjuvant cholylsarcosine on liver tests and plasma cholesterol in primary biliary cirrhosis patients receiving ursodeoxycholic acid. Four primary biliary cirrhosis patients, who, despite more than a year of ursodeoxycholic acid therapy, had one or more liver tests persistently equal to or greater than twice the upper limit of normal, received cholylsarcosine (12-15 mg/kg/day) in addition to ursodeoxycholic acid (13-15 mg/kg/day) for six weeks in an open label study. Values of liver tests and plasma cholesterol, determined every two weeks, remained unchanged. One patient discontinued cholylsarcosine at week 4 because of new-onset pruritus. Analysis of duodenal bile acids in one patient showed 52% enrichment in cholylsarcosine and hydrophilic bile acids constituted 87% of total bile acids. It is concluded that the addition of cholylsarcosine to ursodeoxycholic acid did not influence liver tests in four primary biliary cirrhosis patients who had not responded completely to ursodeoxycholic acid alone. Cholylsarcosine was absorbed and became a dominant biliary bile acid; its administration was associated with increased pruritus.
Assuntos
Colagogos e Coleréticos/uso terapêutico , Ácidos Cólicos/uso terapêutico , Cirrose Hepática Biliar/tratamento farmacológico , Sarcosina/análogos & derivados , Ácido Ursodesoxicólico/uso terapêutico , Adulto , Colesterol/sangue , Quimioterapia Combinada , Feminino , Humanos , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/fisiopatologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Sarcosina/uso terapêuticoRESUMO
BACKGROUND: Inborn errors of bile acid synthesis are newly recognized disorders that may cause the phenotypic appearance of neonatal hepatitis or neonatal cholestasis. METHODS: This is a clinicopathologic study of two sets of siblings with cholestatic neonatal liver failure. RESULTS: In 3 of the infants, diagnostic evaluation, including analysis of urinary bile salts, revealed a predominance of 7 alpha-hydroxy-3-oxo-4-cholenoic and 7 alpha, 12 alpha-dihydroxy-3-oxo-4-cholenoic acids, a pattern consistent with delta 4-3-oxosteroid 5 beta-reductase deficiency, which could be primary or secondary. The fourth infant died before such testing could be carried out. In addition, all 4 infants had histologically disseminated hemochromatosis and met diagnostic criteria for neonatal hemochromatosis. In the 3 infants studied, histologic examination of the liver disclosed giant cell hepatitis with extensive loss of hepatic parenchyma and rapid progression to cirrhosis. Early treatment with ursodeoxycholic acid and cholic acid, previously reported as effective therapy, was given to 2 siblings; it failed to reverse or halt the liver damage, and both infants died. One infant, with the original diagnosis of neonatal hemochromatosis, was treated with a variety of antioxidants and chelation therapy, as recently reported. No improvement was demonstrated, and he went on to liver transplantation. CONCLUSIONS: The presentation of delta 4-3-oxosteroid 5 beta-reductase deficiency as neonatal hemochromatosis may represent a distinct subset of this disorder with an accelerated course, no response to therapy and poor prognosis.
Assuntos
Ácidos e Sais Biliares/metabolismo , Hemocromatose/metabolismo , Erros Inatos do Metabolismo/metabolismo , Oxirredutases/deficiência , Adulto , Biópsia , Colestase Intra-Hepática/etiologia , Colestase Intra-Hepática/patologia , Colestase Intra-Hepática/terapia , Ácido Cólico , Ácidos Cólicos/uso terapêutico , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Recém-Nascido , Fígado/patologia , Falência Hepática/etiologia , Falência Hepática/patologia , Falência Hepática/terapia , Masculino , Prognóstico , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
The efficacy of cholylsarcosine, a synthetic deconjugation-resistant and nonsecretory conjugated bile acid analog for the treatment of fat malabsorption caused by severe bile acid malabsorption, was assessed in an animal model. In two dogs, the ileum and ileocecal valve were resected, causing severe diarrhea, steatorrhea, bile acid malabsorption, and progressive weight loss. Cholylsarcosine was administered as the water-soluble sodium salt by mixing with the dog food. Various doses were explored as well as varying intakes of dog food. Fat absorption was assessed by gravimetric measurement of fecal fat; a nonabsorbable recovery marker (polyethylene glycol mol wt 4000) was used to correct for incomplete fecal collections. Cholylsarcosine caused a 5- to 30-fold increase in fat absorption but had no significant effect on weight loss or fecal weight. Duodenal content was collected during digestion of a meal via a surgically placed Thomas cannula; the aspirates were dilute, acidic, and had a low bile acid concentration. The bile acid concentration increased modestly when cholylsarcosine was administered, but remained below the critical micellization concentration. The results indicate that oral administration of cholylsarcosine improved dietary fat absorption in a canine model of severe bile acid malabsorption with associated steatorrhea and bile acid deficiency in the proximal small intestine. Studies with this compound in patients with nutritional problems because of steatorrhea and severe bile acid malabsorption appear warranted.
Assuntos
Ácidos e Sais Biliares/metabolismo , Ácidos Cólicos/uso terapêutico , Gorduras na Dieta/farmacocinética , Íleo/fisiologia , Síndromes de Malabsorção/tratamento farmacológico , Sarcosina/análogos & derivados , Absorção , Animais , Peso Corporal/efeitos dos fármacos , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Cães , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Conteúdo Gastrointestinal/química , Conteúdo Gastrointestinal/efeitos dos fármacos , Síndromes de Malabsorção/metabolismo , Masculino , Sarcosina/uso terapêutico , Fatores de TempoRESUMO
It was found that in healthy rats cholic acid caused a moderately increased intensity of bile secretion and raised the content of bile acids in it. In animals with toxic hepatitis produced by a long-term action of the chemical poison polychlorpinene in a dose of 1/10 DL50 and following introduction to such rats of cholic acid in a dose of 30 mg/100 g an intensified elinination of cholates and cholesterol excretion were evident. Combined action of polychlorpinene and cholic acid was conductive to a reduced conjugation of cholic acid with taurine and to a greater conjugation with glycine, this being attended by an increased content of free bile acids in the bile.
Assuntos
Bile/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Ácidos Cólicos/uso terapêutico , Inseticidas/intoxicação , Terpenos/intoxicação , Animais , Bile/análise , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Colesterol/análise , Ácidos Cólicos/análise , Ácidos Cólicos/farmacologia , Masculino , RatosAssuntos
Bromelaínas/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Pancreatina/uso terapêutico , Administração Oral , Adulto , Idoso , Bromelaínas/efeitos adversos , Ácidos Cólicos/uso terapêutico , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Avaliação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatina/efeitos adversosRESUMO
Six experiments were conducted with male broiler chicks kept in battery brooders to investigate the effects of feeding diets high in copper on the integrity of the gizzard lining. Conventional and corn starch-soy basal diets were used. Slight improvements in body weight gain and/or feed efficiency were observed when the diets were supplemented with 250 p.p.m. copper as as CuSO4-5HSO, but higher levels (500 to 1000 p.p.m.) depressed growth and decreased feed efficiency. Little or no gizzard erosion was seen in birds fed the practical ration without added copper. Gizzard erosion was observed with 250 p.p.m. copper and the severity of the condition increased with higher levels. With the same level of copper supplementation, severity of gizzard erosion was greater when chicks were fed the corn starch-soy diet than when fed the practical diet. Adding 0.5 p.p.m. selenium to the practical diet containing 1000 p.p.m. copper slightly improved the appearance of the gizzard lining, although the subjective scoring index was significantly (P less than 0.05) lower in only one of two experiments. The addition of zinc, vitamin E, and vitamin B12 did not prevent the gizzard damage caused by high copper levels. Severity of gizzard erosion was significantly reduced by adding 0.35% cholic acid to the semipurified diet with 500 p.p.m. copper, but not to the practical diet with 100 p.p.m. copper. There was no correlation between acidity of the gizzard contents and severity of the erosion.