Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

OBJECTIVES: The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated. METHODS: The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression. RESULTS: CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice. CONCLUSION: Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.

Suplementação de creatina, homocisteínae estresse oxidativo / Creatine supplementation, homocysteine and oxidative stress

A creatina é uma substância popular entre atletas devido a sua possível propriedade ergogênica. Tal popularidade incentivou autores a estudar e explorar o possível potencial terapêutico desta substância. A síntese de creatina é responsável pela maioria das transferências de grupos metila no metabolismo hepático normal. Como a homocisteína é um aminoácido formado exclusivamente a partir da desmetilação da metionina, acredita-se que a creatina e homocisteína estejam metabolicamente conectadas. Estudos têm mostrado que a hiperhomocisteinemia está diretamente ligada à formação de espécies reativas de oxigênio pela auto oxidação da homocisteína e/ou da cisteína e que tal auto-oxidação pode provocar danos celulares.O objetivo desta revisão é discutir aspectos da suplementação com creatina relacionados aos níveis de homocisteína e o estresse oxidativo.

Creatine is a popular substance among athletes due its possible ergogenic property. Such popularity has been stimulating authors to study and explore the possible potencial therapeutic effect of this substance. The synthesis of creatine is responsible for the majority methyl groups transferences in the normal hepatic metabolism. As homocysteine is an aminoacid formed exclusively from the methionine demetilation, it is believed that creatine and homocysteine are metabolically connected. Studies have show that hyperhomocysteinemia is directly linked tooxygen reactive species formation by the homocysteine and/or cysteine auto-oxidation and this can promote cellular damage. The aim of this review is to discuss some aspects of creatine supplementation on homocysteine levels and oxidative stress.