Raymond N. Murdoch

Oxidative stress and the fetotoxicity of alcohol consumption during pregnancy

Pregnant Quackenbush Special mice were exposed to ethanol under semiacute (3.0 g/kg body weight intragastrically, days 7 to 12 of pregnancy), and chronic conditions (15% ethanol in drinking water for 5 weeks before and during pregnancy) to assess whether embryo-fetotoxic actions of the drug involve oxidative stress effects. Effects were monitored both in the maternal system and embryo. Alcohol compromised the maternal system by increasing the generation of lipid peroxides in the liver. It also decreased glutathione and vitamin E levels, and glutathione peroxidase and superoxide dismutase activities in this organ. Glutathione peroxidase activity in the maternal blood decreased. Only minor alcohol-induced changes occurred in the uterine endometrium, including decreased xanthine oxidase and increased gamma-glutamyl transpeptidase. Similarly, only few changes were induced in day-12 embryos by alcohol. In this case, glutathione content and xanthine oxidase activity decreased while glutathione reductase activity increased following exposure to the chronic regime. With the possible exception of the maternal liver where evidence of oxidative damage was detected, these results do not reflect substantial changes in the antioxidant defences of either the pregnant mouse or embryo. However, the changes may contribute to the growth retarding and other fetotoxic effects of alcohol when they are totalled into the multifactorial actions of the drug.

Plasma F2α-isoprostane levels are lowered in pigs fed an (n-3) polyunsaturated fatty acid supplemented diet following occlusion of the left anterior descending coronary artery

Abstract F 2α -isoprostanes, produced non-enzymatically from arachidonic acid are potent vasoconstrictors. Dietary supplementation with (n-3) polyunsaturated fatty acids has been shown to reduce arachidonic acid levels in the body. In the present study, alterations in plasma levels of the F 2α -isoprostane, 8-iso-prostaglandin F 2α , were assessed by enzyme immunoassay in pigs following (n-3) polyunsaturated fatty acid supplementation and during occlusion of the left anterior descending coronary artery. Pigs were fed diets supplemented with either fish oil (rich in n-3 polyunsaturated fatty acids) or beef tallow (high content of saturated fatty acids) for a 6 week period. The animals were then anesthetised and plasma samples were collected. The coronary artery was occluded and the blood samples were collected during the following 10 minutes. While plasma 8-iso-prostaglandin F 2α levels were generally lower in pigs fed the (n-3) fatty acid supplemented diet as compared with those fed the diet high in saturated fats, this response only reached statistical significance (P 2α remained unchanged in both dietary groups once occlusion was initiated. Significant differences (P 2α levels in the porcine circulation in comparison with animals fed beef tallow, particularly after coronary occlusion. This effect compliments the well established action of (n-3) fatty acids in reducing the production of vasoconstrictive eicosanoids.

The metabolic properties of spermatozoa from the epididymis of the tammar wallaby, Macropus eugenii.

The utilization of various substrates by sperm from the cauda epididymidis of the tammar was examined because the major naturally occurring sugar in the semen of this species is N‐acetyl‐D‐glucosamine (NAG) and not fructose, as in eutherian mammals. The sperm displayed a high level of endogenous respiration that supported motility for relatively prolonged periods of time in vitro. They also metabolised exogenous 14C‐labelled glucose, NAG, sucrose, and acetate through glycolytic and/or oxidative processes to produce lactate and 14CO2 at varying rates. The rate of uptake of NAG by tammar sperm was about four times greater than that of other substrates. Glucose and/or NAG stimulated the rate of oxygen consumption by about 20%, but acetate stimulated oxygen consumption by more than 40%. The most striking findings were that NAG almost completely inhibited the oxidation of glucose and sucrose by the sperm and depressed the uptake of glucose, 3‐O‐methylglucose, and sucrose. Acetate oxidation also was inhibited by NAG, but only by about 50%. Tammar sperm generated substantial amounts of free glucose during incubation with NAG, but this and the inhibitory effects of NAG on glucose oxidation were not mimicked by rat sperm.

Changes in Plasma Lipid Homeostasis Observed in Chronic Fatigue Syndrome Patients

A study of 60 CDC-defined chronic fatigue syndrome (CFS) patients and 39 age- and sex-matched controls was undertaken to determine whether there were any alterations in plasma lipid profiles from CFS patients compared with control subjects. Plasma samples were taken from fasted (12 h) subjects and the lipid components were extracted, saponified and analyzed by capillary gas chromatography-mass spectrometry (GC-MS). It was found that CFS patients had different plasma saponified lipid profiles compared with control subjects (standard discriminant function analysis p < 0.02). The first and second most important factors, discriminating the CFS patients from the controls, were a decrease in trans -9-octadecenoic acid and an increase in octadecenoic acid, respectively. The relative abundance of trans -9-octadecenoic acid in the CFS patients was 0.74% compared with 0.99% in the controls ( p< 0.02) and the trans -9-octadecenoic acid:octadecenoic acid ratio was 0.15 in the CFS patients compared with 0.27 in contro...

Teratogenic effects of ethanol in the Quackenbush Special mouse

The intragastric exposure of QS mice to alcohol both under short-term (6-day period) (3.0 g/kg, but not 1.5 g/kg, body weight/day through gestation day (GD) 7 to GD 12) and long-term (chronic) (15% ethanol in drinking water beginning several weeks before mating and continuing into pregnancy) conditions reduced the weight, size, and protein content of GD 12 embryos, and the weight of GD 18 embryos. The incidence of brachydactyly with delayed ossification was also significantly greater in embryos chronically exposed to alcohol than in controls (45% vs. 6.7%). The short-term and long-term exposure regimens produced incidences of only 1% and 5.8%, respectively, of forelimb ectrodactyly in GD 18 embryos. It was concluded that alcohol exerts embryo growth retarding effects in pregnant QS mice without inducing a high incidence of skeletal defects. Thus, the QS mouse could serve as an excellent model to resolve the mechanisms whereby alcohol induces pre- and post-natal growth restrictions during pregnancy.

Assessment of Plasma Fatty Acids and Sterols in Sudden - and Gradual - Onset Chronic Fatigue Syndrome Patients

Purpose: To determine whether sudden - and gradual - onset groups of chronic fatigue syndrome (CFS) patients had characteristic lipid profiles which may be indicative of specific viruses or cytokine responses. Design: Laboratory-based survey. Materials and methods: A study was undertaken in 60 CFS patients and 39 age and sex-matched non-CFS control subjects. Plasma saponified lipid products were assessed using capillary gas chromatography-mass spectrometry (GC-MS) to measure qualitative changes in plasma lipid profiles. Results: Twenty of the CFS patients reported an acute viral-like infection at onset and were assessed for antibodies to Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) whereas the remaining 40 CFS patients reported a gradual onset (G-CFS). None of the sudden-onset patients (S-CFS) had immunological evidence of a current common viral infection. The S-CFS, G-CFS and control groups were well resolved by discriminant function analysis of their lipid profiles (p < 0.0001), where trans-9-octa...

Uterine lipid alterations during early pseudopregnancy and following the artificial induction of decidualization by Concanavalin A in QS mice.

Lipid extracts of whole uterine tissue from mice were examined by gas chromatography‐mass spectrometry during days 2, 3, and 4 of pseudopregnancy (day 1 = copulatory plug) and following the artificial induction of the decidual cell reaction (DCR) on day 4. The range of lipids identified during pseudopregnancy and their percentage composition on day 2 included saturated fatty acids (SFA, 38%), monounsaturated fatty acids (MUFA, 20%), polyunsaturated fatty acids (PUFA, 17%), sterols (25%), long chain alcohols (0.12%), and alkylglycerols (0.11%). Of these, the main components were the fatty acids 16:0 (21%), 18:0 (14%), cis18:1n‐9 (14%), 18:2n‐6 (8.5%), and cholesterol (24%). Although only subtle changes in the composition of uterine lipids occurred through days 2 and 3 of pseudopregnancy, more substantial changes were detected on day 4, at a time when the uterus normally initiates its transient “window of receptivity.” Following induction of the DCR with the lectin Concanavalin A (Con A) at this time, even greater alterations in uterine lipid composition were observed. From 20 to 1,280 min post‐Con A‐treatment the percentage composition of SFA in the treated left uterine horn changed from 43% to 64%, sterols from 19% to 4%, PUFA from 15% to 10%, while MUFA remained unchanged at 23%. The lipid profile of the untreated right uterine horn of these animals was similar to that of the Con A‐treated left uterine horn during the early stages. However, by 1,280 min substantial differences were observed, at a time corresponding with Con A‐induced uterine growth. In contrast, differences in the lipid profile of Con A‐ and saline‐treated uteri were observed at 320 min post‐treatment, a time preceding Con A‐induced uterine growth. Furthermore, the tissue concentration (nmol/mg dry weight) of SFA and sterols in uterine tissue decreased significantly following Con A treatment. The results suggest that uterine lipid changes are implicated in the development of uterine receptivity, and in the remodeling of uterine tissue for successful embryonic invasion and the establishment of pregnancy.