MODIFICATION OF PATHOLOGIC CHANGES IN TOXICOLOGICAL STUDIES DUE TO ENDOTOXIN DERIVED FROM INTESTINAL FLORA I. Microscopic Findings in Various Organs and Tissues from Endotoxin-Treated Rats

• Published in: Journal of Toxicologic Pathology Vol. 6; no. 1; pp. 89 - 104
• Main Authors: Takagi, Hidetoshi, Shimoji, Naoshi, Ogasawara, Hiroyuki, Noguchi, Osamu, Fujii-Murakami, Hisako, Murata, Akiko, Harada, Yasushi, Inomata, Norikazu
• Format: Journal Article
• Language: English
• Published: JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY 1993; The Japanese Society of Toxicologic Pathology
• Subjects: Endotoxin; Microscopic Examination; Rats; Toxicity study
• ISSN: 0914-9198; 1881-915X
• DOI: 10.1293/tox.6.89

In order to clarify the characteristics of the toxic effects of endotoxins on various organs and tissues, single and multiple doses studies of commercial endotoxins were carried out using Fischer and SD rats for the purpose of microscopic examination. In the single dose study using a dose of 10 mg/kg of endotoxin Salmonella typhimurium, changes of the lungs, liver, gastrointestinal tract, and thymus were observed primarily in a tme-dependent manner. After onset of hemorrhagic changes of some organs and tissues at the early stage after dosing, hepatic changes such as activation of Kupffer cells, formation of thrombi and necrosis of hepatocytes, activation of alveolar macrophages and polymorphonuclear cell infiltration in the lungs, and lymphoid depletion of the thymus were observed from 2 or 4 hours after dosing. On the other hand, in the multiple doses study using doses from 0.1 to 1.0mg/kg/day of the same endotoxin, activation of Kupffer cells in the liver and activation of alveolar macrophages in the lungs, and lymphoid depletion of the thymus were observed primarily. We concluded that the endotoxin-modified changes should be taken into consideration when we interprete and judge the results of a general toxicity study of an agent, which has effects related to generation of endotoxins from intestinal flora. Moreover, it is also necessary to understand the different sensitivity to endotoxin among the animal strain for this situation, because the microscopic changes in SD rats due to endotoxin were more prominent to be compared with those in Fischer rats in a single dose study.