Long-Term Supplementation of Black Elderberries Promotes Hyperlipidemia, but Reduces Liver Inflammation and Improves HDL Function and Atherosclerotic Plaque Stability in Apolipoprotein E-Knockout Mice.

SCOPE: HDL particles are protective against atherosclerosis, but may become dysfunctional during inflammation and chronic disease progression. Anthocyanin-rich foods, such as the black elderberry, may improve HDL function and prevent disease development via antioxidant and/or anti-inflammatory effects. This study investigates the long-term consumption of black elderberry extract (BEE) on HDL function and atherosclerosis in apolipoprotein (apo) E-/- mice. METHODS AND RESULTS: ApoE-/- mice (n = 12/group) are fed a low-fat diet, supplemented with 0, 0.25%, or 1% (by weight) BEE (≈37.5-150 mg anthocyanins per kg body weight) for 24 weeks. Feeding 1% BEE increases total serum cholesterol (+31%) and non-HDL cholesterol (+32%) compared with the control diet. PON1 arylesterase (+32%) and lactonase (+45%) activities also increase with the 1% BEE diet. Both 0.25% BEE and 1% BEE diets strongly increase HDL cholesterol efflux capacity (CEC) by 64% and 85%, respectively. Further, BEE dose-dependently lowers serum liver enzymes and hepatic inflammatory gene expression. Although there is no change in neutral lipid accumulation in atherosclerotic lesions, BEE promotes connective tissue deposition in the aortic root. CONCLUSIONS: Chronic BEE supplementation in apoE-/- mice dose-dependently improves HDL function. Despite BEE promoting hyperlipidemia, which likely offsets HDL effects, BEE increases connective tissue content, suggesting improved atherosclerotic plaque stability.

Dietary management of labrador retrievers with subclinical hepatic copper accumulation.

BACKGROUND: Genetic and environmental factors, including dietary copper intake, contribute to the pathogenesis of copper-associated hepatitis in Labrador retrievers. Clinical disease is preceded by a subclinical phase in which copper accumulates in the liver. OBJECTIVE: To investigate the effect of a low-copper, high-zinc diet on hepatic copper concentration in Labrador retrievers with increased hepatic copper concentrations. ANIMALS: Twenty-eight clinically healthy, client-owned Labrador retrievers with a mean hepatic copper concentration of 919 ± 477 mg/kg dry weight liver (dwl) that were related to dogs previously diagnosed with clinical copper-associated hepatitis. METHODS: Clinical trial in which dogs were fed a diet containing 1.3 ± 0.3 mg copper/Mcal and 64.3 ± 5.9 mg zinc/Mcal. Hepatic copper concentrations were determined in liver biopsy samples approximately every 6 months. Logistic regression was performed to investigate effects of sex, age, initial hepatic copper concentration and pedigree on the ability to normalize hepatic copper concentrations. RESULTS: In responders (15/28 dogs), hepatic copper concentrations decreased from a mean of 710 ± 216 mg/kg dwl copper to 343 ± 70 mg/kg dwl hepatic copper after a median of 7.1 months (range, 5.5-21.4 months). Dogs from a severely affected pedigree were at increased risk for inability to have their hepatic copper concentrations normalized with dietary treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Feeding a low-copper, high-zinc diet resulted in a decrease in hepatic copper concentrations in a subset of clinically normal Labrador retrievers with previous hepatic copper accumulation. A positive response to diet may be influenced by genetic background. Determination of clinical benefit requires further study.

Nutritional management of inherited copper-associated hepatitis in the Labrador retriever.

Canine hereditary copper-associated hepatitis is characterized by gradual hepatic copper accumulation eventually leading to liver cirrhosis. Therapy is aimed at creating a negative copper balance with metal chelators, of which D-penicillamine is the most commonly used. D-penicillamine often causes gastro-intestinal side effects and life-long continuous therapy may lead to a deficiency of copper and zinc. The aim of the current study was to investigate the effect of a low-copper, high-zinc diet as an alternative to continuous D-penicillamine treatment for the long-term management of canine copper-associated hepatitis. Sixteen affected Labrador retrievers were followed for a median time period of 19.1 months (range, 5.9-39 months) after being effectively treated with D-penicillamine. The dogs were maintained on a diet containing 1.3±0.3 mg copper/1000 kcal and 64.3±5.9 mg zinc/1000 kcal. Liver biopsies were taken every 6 months for histological evaluation and copper determination. Plasma alanine aminotransferase (ALT) and alkaline phosphatase, as well as serum albumin were determined. Dietary treatment alone was sufficient to maintain hepatic copper concentration below 800 mg/kg dry weight liver in 12 dogs during the study period. Four dogs needed re-treatment with D-penicillamine. ALT activity and albumin concentration were not associated with hepatic copper concentration, but showed a significant association with the stage and grade of hepatitis respectively. In conclusion, a low-copper, high-zinc diet can be a valuable alternative to continuous d-penicillamine administration for long-term management of dogs with copper-associated hepatitis. The copper re-accumulation rate of an individual dog should be considered in the design of a long-term management protocol and in determining re-biopsy intervals.

Dietary management of hepatic copper accumulation in Labrador Retrievers.

BACKGROUND: Copper-associated chronic hepatitis (CACH) recently has been recognized in the Labrador Retriever as an inherited disorder with a late onset of clinical signs. No studies have investigated dietary management for the long-term treatment of this disease or for its potential in delaying the onset of clinical signs in subclinical cases. OBJECTIVES: To investigate the effects of a low-copper diet and zinc gluconate on hepatic copper concentrations in Labrador Retrievers with abnormal hepatic copper concentrations. ANIMALS: Twenty-four client-owned Labradors that were related to patients affected with CACH and that had been diagnosed with increased hepatic copper concentrations. METHODS: Hepatic copper concentrations were assessed before and after an average of 8 and 16 months of treatment. During this time, all dogs were fed exclusively a low-copper diet. In addition, dogs were assigned to 1 of 2 groups in a randomized double-blind manner to receive a supplement of zinc gluconate or placebo. RESULTS: Twenty-one dogs completed the study. Hepatic copper concentrations decreased in both groups at recheck 1 (n = 21; group 1, P < .001; group 2, P= .001) and at recheck 2 (n= 16; group 1, P= .03; group 2, P= .04). No difference in hepatic copper concentrations was found between the 2 groups before treatment (P= .65), at recheck 1 or at recheck 2 (P= .52-.79). CONCLUSIONS AND CLINICAL RELEVANCE: Feeding low-copper diets to Labradors is effective in decreasing hepatic copper concentrations. Adjunctive treatment with zinc does not appear to increase the copper-lowering effects of dietary management.

[Use of dietary fiber in experimental hepatitis in rats]. / Ispol'zovanie pishchevykh volokon pri éksperimental'nom gepatite u krys.

Hepatitis is most widespread form of a lesion of a liver taking an essential place among the causes of invalidity of the population. In present work the created food fibres allocated from various vegetative raw material are described. Is shown the food fibres of bean crops and secondary resources of processing of a grapes improve a general condition of laboratory animals with a liver struck by hepatitis.

[Effectiveness of dietary non-starch polysaccharides in experimental toxic hepatitis]. / Effektivnost' pishchevykh nekrakhmal'nykh polisakharidov pri éksperimental'nom toksicheskom gepatite.

The efficiency of some polysaccharides was investigated in mice with an experimental toxic hepatitis. Hepatitis was induced by the oral administration of 10% solution CCl4 in olive oil at a dosage of 3 ml/kg body weight every day during 7 days. After that tested substances were administrated every day 30-40 min before a feeding at a dosage of 150 mg/kg body weight during 14-21 days. Results showed that a calcium alginate, two low-methoxyl pectins (one with the degree of esterification about 50% and other with the degree of esterification less 5%), fucoidan, and chitozan, but not lambda-carrageenan and kappa-carrageenan, have beneficial affects on liver total lipid, glycogen, malondialdehyde, and diene conjugates as well as on blood total lipid and alanine aminotransferase activity in animals with experimental toxic hepatitis.

[The effect of a diet enriched with food fibers and polyunsaturated fatty acids on the composition of the lipid components in the enterohepatic circulation system in rabbits with cholestasis]. / Vliianie ratsiona, obogashchennogo pishchevymi voloknami i polinenasyshchennymi zhirnymi kislotami, na sostav lipidnykh komponentov v sisteme pechenochno-kishechnoi tsirkuliatsii u krolikov pri kholestaze.

In experiments on rabbits that had undergone partial constriction of the choledochus, the development of calculous hepatocholecystitis was observed in a half of the operated on animals. No biliary calculi were detected in the animals that received the ration enriched with food vegetable fibres, beta-sitosterol and linoleic polyunsaturated fatty acids after similar operations.