da Silva, Vitor Manuel Fernandes Seabra; (1995) The possible hepatoprotective role of taurine: an in vivo and in vitro study. Doctoral thesis (Ph.D), UCL (University College London).

Preview

Text The_possible_hepatoprotective_.pdf Download (23MB) | Preview

Abstract

The experiments described in this thesis aimed to examine the possible protective role of taurine against the hepatotoxic effects caused by two cholangiodestructive compounds, α-naphthylisothiocyanate (ANIT) and 4,4'- diaminodiphenylmethane (DAPM). Studies investigated the protective effect of taurine in vivo and in vitro, using respectively male Sprague-Dawley rats and freshly isolated rat hepatocyte suspensions. Control animals fed a normal diet and tap water were investigated for their response after being dosed with ANIT and DAPM. When liver taurine levels were raised by giving taurine in the drinking water, rats were slightly less susceptible to ANIT- and DAPM- induced hepatotoxicity than control animals. Two taurine uptake inhibitors (β- alanine and guanidinoethane sulphonate (GES) were given in the drinking water to decrease liver taurine levels. Both compounds were effective in decreasing the liver levels of taurine, β-alanine treated animals were more susceptible, to a certain extent, than control animals to the hepatotoxic effects of both compounds tested. Conversely, GES did not increase rat susceptibility to either of the toxicants. When the time-course of DAPM-induced hepatotoxicity was studied, taurine pretreatment to rats shifted the development of hepatotoxicity to an eairlier time point (12-18 hours) by a mechanism that appears to be connected with an increased bile flow. This might explain the slight protection observed when a later time point (24 hours) was assessed. A different approach to modulate liver taurine levels was taken by feeding a semi-synthetic, taurine-free, 15% or a 30% casein diet to rats. Although animals fed the higher content casein diet showed a meaningful difference in urinary taurine excretion throughout the study, their liver levels at the time of dosing were comparable to their counterparts fed the 15% casein diet. Taurine urinary excretion seemed to be the path used by the rat to eliminate the excess of sulphur in the diet. Animals fed these diets and dosed with ANIT or DAPM were shown to be less susceptible than animals fed a normal diet when serum biochemical parameters were assessed but the lack of correlation with the histopathological evaluation leads to the conclusion that these protective effects should be further investigated and should be regarded with caution. The cytoprotective properties of taurine against the cytotoxic effects of ANIT and DAPM were also tested. Both compounds caused a depletion of intracellular GSH and ATP. Cells isolated from β-alanine treated animals showed lower levels of taurine but they were not more susceptible to ANIT than hepatocytes isolated from control rats. When taurine was added to hepatocytes isolated from control or β-alanine treated animals no protection was afforded. Cysteinesulphinate, a taurine metabolic precursor, added to hepatocytes in suspension afforded a slight protective effect against ANIT cytotoxicity. These studies have shown that taurine afforded some hepatoprotection against tested toxicants.

Download activity - last month

Export as CSVXMLJSON

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as JSONCSVXML

Archive Staff Only

View Item