Inflammatory, immunological and histopathological parameters of prolonged administration of Ipomoea carnea in rats: 1. Evaluation of adult animals 2. Perinatal study

Author(s)

Isis Machado Hueza

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD)
• Defense date: 2006-11-10

Examining board members

Silvana Lima Górniak; Maria Lucia Zaidan Dagli; Célia Aparecida Paulino; Márcia Guimarães da Silva; Helenice de Souza Spinosa

• Advisor: Silvana Lima Górniak

Abstract

The aim of this study was to evaluate the toxic effect of I. Carnea and its toxins on the immune system of rats, and to evaluate its effects on mothers and offspring when administered to dams during gestation or lactation. An alkaloid-rich plant extract (RAF) was added to drinking water to obtain doses equivalent to 3.0 and 15.0g/kg of dry leaves for 14 and 21 days, and a dose of 15.0 g/kg by gavage for 14 days. Macrophage activity (MO), and chronic and acute inflammation induced by BCG and carragenine, respectively, were evaluated. Each toxin in I. carnea (i.e., swainsonine and calystegines B1, B2, B3 and C1) was administered by gavage to female rats, in similar concentrations as contained in 15.0g/kg of RAF during 14 days to evaluate MO. The RAF was dosed by gavage in pregnant or nursing rats at 1.0, 3.0, 7.0 and 15.0g/kg. Cross-fostering was used to evaluate placental passage of swainsonine; swainsonine concentration was determined in amniotic fluid and in milk. On postpartum day 70 the litters were evaluated for MO and chronic and acute inflammation. Immunotoxic responses were evaluated in young and adult rats treated with RAF for 14 days. Tissue samples were then harvested for histopathology. The immune function of adult rats was enhanced by lower doses of the RAF. Phagocytosis and hydrogen peroxide production were improved, and there was enhancement of chronic immunity, but suppression of acute inflammatory responses. Among the I.carnea alkaloids, only swainsonine showed toxicity. The litters of dams treated with swainsonine during gestation or lactation showed a reduction in body weight at birth and after lactation, respectively. Swainsonine clearly passed through the placenta, and was found in amniotic fluid, and in milk. There were no effects on the immunity of litters from mothers treated during gestation or lactation. However, pups from mothers dosed with swainsonine during lactation had an increased occurrence of arthritis. Further, young rats showed thymus atrophy, whereas adults developed splenomegaly and reduced bone marrow cellularity. Finally, animals of all ages showed enhanced antibody titers. Only CNS tissue did not have the characteristic vacuolar degeneration typical of I. Carnea toxicosis. In conclusion, low doses of RAF enhanced MO activity. Among the I. Carnea alkaloids, only swainsonine showed toxicity. Swainsonine passed the placental barrier, resulting in smaller litters with diminished birth weights. Swainsonine was also excreted in milk, resulting in vacuolar lesions in pups, as well as thymus atrophy, which could cause autoimmunity in adulthood. Finally, even with higher doses, CNS tissue in rats is resistant to the toxic effects of swainsonine. (AU)

• FAPESP's process: 01/11444-0 - Inflammatory, immunological and histopathological parameters of prolonged administration of Ipomoea carnea in rats: 1. Evaluation of adult animals. 2. Perinatal study
• Grantee: Isis Machado Hueza
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)