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.

Protective Effect of Selenium-Enriched Red Radish Sprouts on Carbon Tetrachloride-Induced Liver Injury in Mice.

This study aimed to investigate the effect of Se (Selenium) treatment on nutritional quality in radish sprouts. The results showed that 15 µM sodium selenite significantly increased phenolics compounds, flavonoids compounds, anthocyanins, and some essential amino acid content, while improving the total antioxidant capacity of radish sprouts. Besides, the Se-enriched radish sprouts significantly alleviated the liver damage caused by carbon tetrachloride (CCl4 ) in mice and improved the antioxidant capacity of the liver in mice, whereas the Se-enriched radish sprouts alleviated the inflammatory reaction and apoptosis caused by CCl4 . These results imply that Se-enriched radish sprouts have a positive impact on mice with CCl4 -induced liver injury, and that in future Se-enriched radish sprouts could be developed into an effective food and health care product for the liver injury prevention. PRACTICAL APPLICATION: Because selenium is an essential trace element in the human body, selenium-enriched sprouts can help eliminate free radicals in the body, relieve aging, and selenium-deficient diseases. They are easy to grow and have low costs. Hence, selenium-enriched sprouts have a great potential of being widely consumed.

Diet restriction enhances compensatory liver tissue repair and survival following administration of lethal dose of thioacetamide.

Diet restriction is known to prevent a plethora of age-associated diseases including cancer. However, the effects of diet restriction on noncancer end points are not known. The objective of this study was to investigate whether diet restriction protects against hepatotoxicity of thioacetamide (TA), and if so, to investigate the underlying mechanism. Male Sprague-Dawley rats (250-275 g) were maintained on 65% of their ad libitum (AL) food consumption for a period of 3 weeks and then treated with a single low dose of 50 mg TA/kg i.p.. Plasma enzymes (ALT and SDH), hepatic glycogen levels, and 3H-thymidine incorporation into hepatocellular nuclear DNA were measured during a time course (0-120 h) after TA administration. Liver sections were examined for histopathology, and cell-cycle progression was assessed by proliferating cell nuclear antigen (PCNA) immunohistochemistry. In AL rats hepatic necrosis was evident at 12 h, peaked at 36 h, persisted up to 72 h, and was resolved by 96 h. In the diet-restricted (DR) group hepatic necrosis was observed at 12 h, peaked at 24 h, persisted till 72 h, and was resolved by 96 h. Maximal injury indicated by enzyme elevation occurred in DR rats and was approximately sixfold greater than that observed in the AL group. Histopathological examination of the liver sections revealed liver injury concordant with plasma enzyme elevations. There was a higher and sustained S-phase synthesis in the DR rats compared to AL group. S-phase stimulation was evident at 36 h, peaked at 48 h, and persisted until 96 h in the DR rats, whereas in the AL rats peak S-phase stimulation occurred at 36 h and subsided by 72 h. PCNA studies revealed a corresponding stimulation of cell-cycle progression indicating highly stimulated compensatory tissue repair. The 14-day lethality experiments (600 mg TA/kg i.p.) indicated 70% survival in the DR rats compared to 10% survival in the AL group. Although diet restriction increases hepatotoxic injury of TA, it protects from the lethal outcome by enhanced liver tissue repair. Comparison of liver injury and tissue repair employing an equitoxic dose (600 mg TA/kg in AL rats yields similar liver injury as observed with 50 mg TA/kg in DR rats) revealed that in spite of near equal injury up to 36 h, tissue repair response in DR rats is much higher. The compensatory tissue repair allows the DR rats to escape death in contrast to much lower compensation in AL rats leading to progression of liver injury culminating in death.