Liver genomic responses to ciguatoxin: evidence for activation of Phase I and Phase II detoxification pathways following an acute hypothermic response in mice

Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (p ≤ 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Data were filtered (|fold change| ≥ 1.5 and p ≤ 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4°C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene expression in pathways involving eicosanoid biosynthesis and cholesterol homeostasis was also noted. Cytochrome P450s (Cyps) were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial downregulation at 1 h but were quickly and strongly upregulated at 4 and 24 h post-exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice.

The Grassholme Channels

The design and construction of four experimental channels at Grassholme reservoir in Teesdale, County Durham (UK) are briefly described. The problem of obtaining valid replication between channels is examined using published data obtained for previous experiments in the channels. It is concluded that replication may be obtained by careful experimental design. The limitations of the existing configuration of pipework and channel design are discussed and solutions suggested. Finally a list of the main components of the channels and suppliers is appended. Alternative materials and suppliers could well be found for most items. (PDF contains 23 pages)

Calibration of Grassholme Channels, 1982

Adjustment of experimental channels to give any specified pattern of water depth or velocity is complex and tedious because it involves a number of variables. Since some variables are not controllable and variables may interact, valve settings of the Grassholme channels were initially determined on an ad hoc basis to suit individual experiments. This method was used during 1982 but additional observations were made in order to gain more detailed understanding of the channel system and, as far as possible, to develop a guide to future short-cuts in attaining suitable channel settings for any given purpose. This report describes calibration of the Grassholme channels (using water of the Grassholme Reservoir) for the biological experiments of spring - summer 1982. The main variables that are discussed are valve turns and discharge and velocity and depth. It also seeks to establish relationships which will be of value in future managment of the channels for experimental purposes.

Experiments on downstream movement of recently emerged trout and salmon parr in Grassholme channels, 1983-1985

A number of authors have described the manner in which young salmonids, soon after emergence from the gravel, set up and defend territories. This leads to mortality or downstream displacement of the individuals which are unable to acquire territories and is widely accepted as the main method of population regulation amongst young salmonids. In some field experiments the fish were constrained in screened reaches and the option of downstream dispersal for the surplus fry was thus excluded. In order to explore some aspects of downstream dispersal more closely under conditions which gave more control than is obtained in a natural stream, four experimental channels were set up at Grassholme reservoir in Teesdale. The report describes the results of investigations on the timing and rate of downstream movement of young brown trout (Salmo trutta L.) and Atlantic salmon (Salmo salar L.) out of experimental channels, with special reference to the effect of water velocity on the rate of ”emigration”.