Early phase of amyloid beta42-induced cytotoxicity in neuronal cells is associated with vacuole formation and enhancement of exocytosis

Amyloid beta (Abeta) neurotoxicity is believed to play a critical role in the pathogenesis of Alzheimer's disease (AD) mainly because of its deposition in AD brain and its neuronal toxicity. However, there have been discrepancies in Abeta-induced cytotoxicity studies, depending on the assay methods. Comparative analysis of Abeta42-induced in vitro cytotoxicity might be useful to elucidate the etiological role of Abeta in the pathogenesis of AD. In this study, MTT, CCK-8, calcein-AM/EthD-1 assays as well as thorough microscopic examinations were comparatively performed after Abeta42 treatment in a neuronal precursor cells (NT2) and a somatic cells (EcR293). Extensive formation of vacuoles was observed at the very early stage of Abeta42 treatment in both cells. Early observation of Abeta42 toxicity as seen in vacuole formation was also shown in MTT assay, but not in CCK-8 and calcein-AM/EthD-1 assays. In addition, Abeta42 treatment dramatically accelerated MTT formazan exocytosis, implying its effect on the extensive formation of cytoplasmic vacuoles. Abeta42 seems to cause indirect inhibition on the intracellular MTT reduction as well as vacuole formation and exocytosis enhancement. Following the acute cellular dysfunction induced by Abeta42, the prolonged treatment of micromolar concentration of Abeta42 resulted in slight inhibition on redox and esterase activity. The early Abeta42-induced vacuolated morphology and later chronic cytotoxic effect in neuronal cell might be linked to the chronic neurodegeneration caused by the accumulation of Abeta42 in AD patients' brain.

Male reproductive toxicity of phosphamidon: histopathological changes in epididymis.

Phosphamidon, a neurotoxic insecticide, was tested for male reproductive toxicity with special reference to the epididymis. The insecticide was fed to Wistar strain male albino rat at 35 ppm concentration in drinking water ad libitum for 30 days. After vascular perfusion, thin slices of caput and cauda epididymidis were embedded in plastic, cut at 1 micron thickness and stained in toluidine blue for light microscopic observation. Principal cells of the caput epididymidis were vacuolarized and seen to pinch off fragments apically. In the proximal cauda the clear cells increased in height and in the size of the secondary lysosomal granules. In the distal cauda the clear cells appeared swollen out of proportion. Phosphamidon appears to affect the principal cells indirectly through its toxic effect on the Leydig cells; the clear cells of the cauda appear to be directly vulnerable to the toxic action of the pesticide.

Action of metronidazole on Entamoeba histolytica: an ultrastructural study.

Metronidazole (19 micrograms/ml) caused progressive increase in vacuolization in Entamoeba histolytica cells with disintegration of its plasma membrane leading to almost complete disappearance of the latter within 3 hours. The drug also induced formation of helical ribosomal aggregates in the cytoplasm and disappearance of button like structures inside the nucleus.

Effect of sodium selenite on the hepatotoxicity induced with carbon tetrachloride

The authors have demonstrated the effect of sodium selenite on the hepatotoxicity due to carbon tetrachloride, by observing the distribution and disaggregation of the pyroninophilic granules in the hepatic cell of the mature male albino mice. Each experimental mouse of the selenite and the selenite plus carbon tetrachloride groups was given a single dose of 4 ug. of sodium selenite per kilogram of body weight and that of the control and the carbon tetrachloride groups was given 0.1 ml. of distilled water alone. Six hours after the first administration of distilled water or sodium selenite, the experimental mice of the carbon tetrachloride and the selenite plus carbon tetrachloride groups were given a single dose of l.0 ml. of carbon tetrachloride per kilogram of body weight and those of the selenite groups were given 0.l ml. of paraffin oil alone. Following the 1ast administration of carbon tetrachloride or paraffin oil, the mice were sacrificed by bleeding (cutting the common carotid artery) at the intervals of 2,3,4,6,8, and 12 hours respectively. Histochemical preparations were stained by the methyl-green and pyronin method and oil red 0 method. The hepatotoxicity due to the administration of carbon tetrachoride was evident in the hepatic cells; the pyroninophilic granlues were partly reduced in volume in the hepatic cells of the centrilobular and the intermediate zones as early as the 3 hour-period, and markedly reduced or disappeared in the centrilobular and some part of the intermediate zones associated with hydropic degeneration as well as in the 6 hour-period. Thereafter marked reduction or dissolution of the pyroninophilic granules was found and extended as the periportal zone at the 12 hour-period. However, the pyroninophilic granules in the hepatic cells of selenite plus carbon tetrachbride group showed no significant changes in the hepatic cells of these zones, compared to the histochemical feature of the granules in the hepatic cells of the control and the selenite groups. Consequently it is suggested that the lipid peroxidative decomposition of the microsomal membranes, which is induced with carbon tetrachloride, would be prevented by a previous administration of sodium selenite.