Establishing rat HSOS model induced by pyrrolizidine alkaloid (Monocrotaline)
SUBMITTED BY: ABDULHUSSEIN ALI HUSSEIN
SUPERVISED BY: SUN LIXIN
ABSTRCT:
Our Objective is to establish the hepatic sinusoidal obstruction syndrome (HSOS) model of pyrrolizidine alkaloids (monocrotaline) in rats, and to conduct in vivo experiments with monocrotaline. After administration, the liver pathological indexes were detected, including blood biochemical parameters, HE pathological findings.
BACKGROUND:
pyrrolizidine alkaloids p(PAs) are one of the major hepatotoxicity components in plants. Chinese herbal medicines containing pyrrolizidine alkaloids are still widely used in clinical practice in China. Investigation shows that at least 40 common traditional Chinese medicines or folk medicines contain pyrrolizidine alkaloids, Some of them are collected by Chinese pharmacopoeia, such as Senecio, Flos Farreri, Perrin, Lithospermum, etc., and are widely used in Chinese patent medicine preparations(1) Due to the lack of detailed research on some Chinese herbal medicines containing pyrrolizidine alkaloids, some of them contain pyrrolizidine alkaloids but lack of safety limits, so there are hidden dangers in clinical application. The alkaloid used for the current study, monocrotaline, is not toxic until it undergoes metabolic activation to a pyrrolic metabolite(2). Activation of monocrotaline takes place only in the liver via cytochrome P-450,23,24 and detoxification of monocrotaline pyrrole occurs by conjugation to glutathione(2). The hepatotoxicity of pyrrolizidine alkaloids is mainly due to hepatic sinus obstruction syndrome (HSOS)(3). Liver cell hemorrhagic necrosis, liver giant cell disease and so on. In addition, pyrrolizidine alkaloids also have mutagenicity, carcinogenicity, teratogenicity and other toxicity. In China, the number of clinical cases of sinus obstruction syndrome caused by taking a drug containing pyrrolizidine alkaloids is increasing. The onset of pyrrolizidine alkaloids is characterized by hepatic veno-occlusion due to damage and exfoliation of hepatic sinusoid endothelial cells. As the disease progresses, it eventually develops into congestive hepatic fibrosis (4), Although many reports have been reported on the liver injury of pyrrolizidine alkaloids, the exact toxic mechanism of pyrrolizidine is still to be studies.
In this study, in-vivo studies were conducted and examined changes induced by monocrotaline, a pyrrolizidine alkaloid that induces sinusoidal obstruction syndrome in rat.
METHOD:
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