In Vivo Study for Measuring the Toxicity of Heat Stable Enterotoxin (a) Produced by Enterotoxigenic Escherichia coli in Mice

Abstract

This research was conducted to measure the safety of heat stable enterotoxin a (STa) produced by enterotoxigenic Escherichia coli, through studying its toxic effect on mice since it showed a promising effect in reducing the proliferation of colorectal cancer cells. The cytogenetic effect was determined after giving five different doses (100, 200, 400, 800 and 1600)µg/Kg in comparison with negative (phosphate buffer saline / PBS) and positive (mitomycin C/ MMC, at doses of 2 and 5µg/Kg) controls on mouse bone marrow cells by employing the following parameters: mitotic index, chromosomal aberrations and micronucleus, also, the serum level of liver functional enzymes (GOT, GPT, ALP) was recorded. In addition, lethal dose 50 (LD 50) with certain clinicopathological changes in five organs (colon, kidney, liver, stomach and lung) was also determined after oral administration of STa for ten successive days and at two doses (500 and 1000) µg/Kg. Results showed that, none of the five different doses of STa caused any significant changes in the three examined cytogenetic parameters in the mouse bone marrow cells; precisely, neither the low dose nor the high one of STa caused reduction or induction in these parameters. In fact, clear effect in decreasing mitotic activity and increasing spontaneous frequencies of both chromosomal aberrations and micronucleus was revealed after MMC treatment. Furthermore, significant differences in mouse serum level of the three enzymes were not seen at any doses of STa, while significant reduction in the levels of these enzymes was noticed after treatment with the two doses of MMC. In this study the LD 50 test was used to investigate the lethal effect of the partially purified STa, and it was shown to be not lethal to mice at both doses of (500 and 1000) µg/Kg, since death was not recorded, moreover, no clinicopathological effects were indicated in the all examined mouse tissues, however the only noticed clinical sign was diarrhea with all doses, which was observed after three days of STa treatment.