Search PubMed⌕ Search

Biomedical subjects

T F Slater

Publications and source records attributed to T F Slater.

154 records · Page 9Linked to original sources

Changes in lysosomal enzymes in acute experimental liver injury.

1. An investigation has been made of the changes occurring in lysosomal enzyme activities during the early development of experimentally produced liver injury in the rat. Three enzymes have been studied: acid phosphatase, acid ribonuclease and beta-glucuronidase. Four different methods of inducing liver injury have been used: administration of carbon tetrachloride, thioacetamide, dimethylnitrosamine and the fungal toxin sporidesmin. 2. The majority of the data presented concern alterations produced by carbon tetrachloride. Despite the extensive central necrosis and accompanying fat accumulation which this poison produced in the liver, only small changes in the activity and latency of lysosomal enzymes could be detected. In the early (pre-necrotic) period of injury these changes were insignificant. At a late stage of injury, when extensive centrilobular necrosis was present, there were indications of lysosomal rupture. 3. The results obtained with the other three hepatotoxins were similar to those described for carbon tetrachloride in that no evidence of early lysosomal rupture was obtained during the pre-necrotic period. It is concluded that lysosomes probably play no role in the early development of the four types of liver injury studied but, instead, are involved in later scavenging processes.

Acid Phosphatase↗

Mechanisms of protection against the damage produced in biological systems by oxygen-derived radicals.

This paper will concentrate on the damage to liver endoplasmic reticulum and plasma membrane fractions that results from exposure to O2- derived radicals and lipid peroxidation. Lipid peroxidation in rat liver endoplasmic reticulum can be produced in various ways involving electron flow out of the NADPH-cytochrome P450 electron-transport chain; analogous reactions occur also in liver plasma membrane suspensions. The subsequent damaging reactions of oxygen-derived radicals and of lipid peroxidation on biological components can be attenuated by various free-radical scavengers and a survey of more than 50 such scavengers in four different systems involving lipid peroxidation has been made. The conditions required for such scavenging reactions to be effective will be outlined, and the difficulties inherent in using such scavengers in vivo will be discussed.

Aldehyde Oxidoreductases↗

Manipulation of myocardial alpha-tocopherol levels fails to affect reperfusion arrhythmias or functional recovery following ischemic challenge in the rat heart.

Antioxidants that act as free radical scavengers have the potential to inhibit lipid peroxidation. It has previously been proposed that a relationship exists between free radicals, lipid peroxidation and reperfusion-induced arrhythmias. We have therefore examined the ability of the lipid-soluble antioxidant, alpha-tocopherol, to decrease the incidence of reperfusion-induced arrhythmias. We have shown that the myocardial alpha-tocopherol content can be significantly increased from its control value of 65.3 +/- 5.6 nmoles/g wet wt of heart to 115.0 +/- 15.6 nmoles/g wet wt of heart (p less than 0.01) by chronic intraperitoneal pretreatment and that it can be decreased, to 21.1 +/- 3.7 nmoles/g wet wt of heart (p less than 0.01), by chronic dietary manipulation. Rat hearts isolated from either of these groups, or from placebo-treated control animals, were subjected to 5 or 10 min coronary artery occlusion and were subsequently reperfused; there were no significant differences between the incidence and duration of VF and VT or the incidence and number of VPBs in these three groups. The effect of alpha-tocopherol manipulation on metabolic and functional recovery of working hearts subjected to 20 min global ischemia was subsequently examined and no significant changes were observed. Cardiac output recovered to 82 +/- 4, 81 +/- 6 and 76 +/- 5% of its preischemic value in the control, enriched and depleted groups, respectively. In conclusion, myocardial alpha-tocopherol content appears to bear no relation to the severity of reperfusion-induced arrhythmias or to the resistance of the heart to ischemic injury.

Adenosine Triphosphate↗