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WHO monographs on selected medicinal plants - travolekar.ru

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<str<strong>on</strong>g>WHO</str<strong>on</strong>g> <str<strong>on</strong>g>m<strong>on</strong>ographs</str<strong>on</strong>g> <strong>on</strong> <strong>selected</strong> <strong>medicinal</strong> <strong>plants</strong><br />

ti<strong>on</strong>. At the time of death (day 20), blood from portal and peripheral veins,<br />

and samples from intestinal mucosa, amni<strong>on</strong>, amniotic cells and placenta<br />

were collected, and the tissues were cultured in the presence of ricinoleic<br />

acid or indometacin. The c<strong>on</strong>centrati<strong>on</strong>s of prostaglandin E2 in the media<br />

or blood were measured by radioimmunoassay methods. The prostaglandin<br />

E2 levels in the portal vein increased; the prostaglandin E2 levels in<br />

peripheral blood showed no significant changes; the prostaglandin E2 levels<br />

in the tissues of the intestinal mucosa, placenta, amni<strong>on</strong> and amniotic<br />

cells were increased. Ricinoleic acid stimulated the synthesis of prostaglandin<br />

E2 in the tissues in vitro (27).<br />

Toxicology<br />

Toxicity studies <strong>on</strong> castor oil have been performed by incorporating the<br />

oil into feed rati<strong>on</strong>s at c<strong>on</strong>centrati<strong>on</strong>s as high as 10% of the diet. Animals,<br />

F344/N rats and B6C3F1 mice, of both sexes were fed the diet for<br />

13 weeks. Exposure to castor oil at dietary c<strong>on</strong>centrati<strong>on</strong>s as high as 10%<br />

in 13-week studies did not affect survival or body weight gains of rats or<br />

mice (10 per sex and dose). No biologically significant effects were noted<br />

in haematological analyses in rats. Small increases in total bile acids and in<br />

se<strong>ru</strong>m alkaline phosphatase were noted at various times during the studies<br />

in rats receiving the higher dietary c<strong>on</strong>centrati<strong>on</strong>s of castor oil. Liver<br />

weights were increased in male rats receiving the 10% dietary c<strong>on</strong>centrati<strong>on</strong><br />

and in male and female mice receiving diets c<strong>on</strong>taining 5% or 10%<br />

castor oil. However, no histopathological lesi<strong>on</strong>s were associated with<br />

these liver changes, nor were there any compound-related morphological<br />

changes in any organ in rats or mice. Thus, no significant adverse effects<br />

of castor oil administrati<strong>on</strong> were noted (28).<br />

Epithelial cells, isolated from small intestine of hamsters, were used to<br />

measure in vitro cytotoxicity of the c<strong>ru</strong>de d<strong>ru</strong>g. The cytotoxicity of ricinoleic<br />

acid (castor oil) was assessed by:<br />

— exclusi<strong>on</strong> of trypan blue;<br />

— release of intracellular (prelabelled) 51Cr; and<br />

— inhibiti<strong>on</strong> of cellular uptake of 3-O-methylglucose.<br />

Ricinoleate produced weak but dose-dependent (0.1–2.0 mM) cytotoxicity<br />

as assessed by all three methods (29).<br />

In an in vivo study, segments of rabbit ileum were examined by scanning<br />

electr<strong>on</strong> microscopy after exposure to various compounds known to<br />

stimulate fluid secreti<strong>on</strong> in the small intestine. After perfusi<strong>on</strong> with ricinoleate<br />

(castor oil) at a c<strong>on</strong>centrati<strong>on</strong> of 10 mM, striking changes were<br />

observed at villus tips and <strong>on</strong> the apicolateral surfaces of villi; erosi<strong>on</strong>s of<br />

the tips were c<strong>on</strong>firmed by light microscopy of the same pieces of tissue<br />

276

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