Acute Toxicity Assessment: Macroscopic and Ultrastructural Effects in Mice Treated with Oral Tetrodotoxin.

Tetrodotoxin (TTX) is an extremely toxic marine compound produced by different genera of bacteria that can reach humans through ingestion mainly of pufferfish but also of other contaminated fish species, marine gastropods or bivalves. TTX blocks voltage-gated sodium channels inhibiting neurotransmission, which in severe cases triggers cardiorespiratory failure. Although TTX has been responsible for many human intoxications limited toxicological data are available. The recent expansion of TTX from Asian to European waters and diversification of TTX-bearing organisms entail an emerging risk of food poisoning. This study is focused on the acute toxicity assessment of TTX administered to mice by oral gavage following macroscopic and microscopic studies. Necropsy revealed that TTX induced stomach swelling 2 h after administration, even though no ultrastructural alterations were further detected. However, transmission electron microscopy images showed an increase of lipid droplets in hepatocytes, swollen mitochondria in spleens, and alterations of rough endoplasmic reticulum in intestines as hallmarks of the cellular damage. These findings suggested that gastrointestinal effects should be considered when evaluating human TTX poisoning.

Assessment of a tissue-engineered gastric wall patch in a rat model.

Stenosis or deformity of the remaining stomach can occur after gastrectomy and result in stomach malfunction. The objective of this study is to demonstrate the feasibility of transplanting a tissue-engineered gastric wall patch in a rat model to alleviate the complications after resection of a large area of the gastric wall. Tissue-engineered gastric wall patches were created from gastric epithelial organoid units and biodegradable polymer scaffolds. In the first treatment group, gastric wall defects were created in recipient rats and covered with fresh tissue-engineered gastric wall patches (simultaneous transplantation). In the second treatment group, the tissue-engineered gastric wall patches were frozen for 12weeks, and then transplanted in recipient rats (metachronous transplantation). Tissue-engineered gastric wall patches were successfully used as a substitute of the resected native gastric wall in both simultaneous and metachronous transplantation groups. The defrosted wall patches showed almost the same cell viability as the fresh ones. Twenty-four weeks after transplantation, the defect in the gastric wall was well-covered with tissue-engineered gastric wall patch, and the repaired stomach showed no deformity macroscopically in both groups. Histology showed continuous mucosa and smooth muscle layers at the tissue-engineered stomach wall margin. The feasibility of transplanting a tissue-engineered patch to repair a defect in the native gastric wall has been successfully shown in a rat model, thereby taking one step closer toward the transplantation of an entire tissue-engineered stomach in the future.

An ultrastructural assessment of mitochondrial in the gastric parietal cell with the high iron diamine methods.

The ultrastructural densification of mitochondria by the high iron diamine (HID) method has been investigated by staining gastric parietal cells with each component of the HID reagents, alone or in combination, or with an otherwise modified HID solution. The effect of certain chemical treatments prior to staining has also been assessed. These tests provided evidence for at least three cytochemically distinguishable constituents in the mitochondrial matrix. In addition, the results from these tests and observation obtained with a newly introduced diaminobenzidine (DAB)-FeCl3 staining reagent indicated that the probable mode of action of the HID method in imparting density to mitochondrial matrix entails combination between a complex of iron with polymerized or aggregated m- and p-diamine and some matrix constituent. Assessment of the cytochemical staining in varied fixation condition revealed that the lucent population of mitochondria recently described in HID-stained parietal cells reflects a failure to stain with the method because of inadequate fixation. The possible nature of the HID-reactive substance in the mitochondrial matrix is discussed in the light of these observations and other cytochemical reactivities.