Pyrrolizidine alkaloid clivorine induced oxidative injury on primary cultured rat hepatocytes

Abstract

<jats:p> Clivorine is an otonecine-type hepatotoxic pyrrolizidine alkaloid (HPAs), to which humans are exposed when consuming herbs containing such components. In the present study, we investigated clivorine-induced oxidative stress injury on primary cultured rat hepatocytes. Rat hepatocytes were treated with various concentrations of clivorine (1—100 μM) for 48 hours, and then cell viability was detected by 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay, while lipid peroxidation (LPO) level, glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) activities were determined to evaluate the oxidative injury. The results of MTT assay showed that clivorine decreased cell viability in a concentration-dependent manner. Clivorine also increased LPO amounts in rat hepatocytes at the concentrations of 50 μM and 100 μM. Further results showed that clivorine decreased GPx, GST and GR activities, which are all reduced glutathione (GSH)-related antioxidant enzymes. CAT and SOD are both important antioxidant enzymes, and the results showed that clivorine increased CAT activity at the low concentration of 5 μM and decreased cellular SOD activity at all concentrations. Taken together, our results demonstrated that clivorine induced toxicity on primary cultured rat hepatocytes by causing the damage on cellular redox balance. </jats:p>

Quercetin Prevents Pyrrolizidine Alkaloid Clivorine-Induced Liver Injury in Mice by Elevating Body Defense Capacity

“…We found in our previous reports that PA clivorine can induce apoptotic cell death and oxidative stress injury in human normal liver L-02 cells [7], [8]. The present results of TUNEL assay and Western-blot analysis of caspase-3 demonstrate that quercetin prevented clivorine-induced apoptotic cell death.…”

“…L. hodgsonii Hook and L. Dentata , which belong to genus Ligularia and the family Asteraceae, are native to China and Japan [6]. We already demonstrated in our previous studies the involvement of oxidative stress injury and apoptosis in clivorine-induced hepatotoxicity [7], [8]. N-Acetyl-Cysteine and S-adenosyl methionine, which are the precursors for cellular GSH biosynthesis, can reverse clivorine-induced hepatotoxicity by increasing cellular GSH level [9], [10].…”

Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

“…To evaluate any species-dependent effects of some DHPAs, primary hepatocyte cultures from eight-week-old male chicks, mice, and rats were developed using modifications of a previously described method [37]. The hepatocytes were allowed to establish for 12 h in a 96-well plate.…”

Extraction Optimization, Preliminary Characterization and Bioactivities in Vitro of Ligularia hodgsonii Polysaccharides

“…On the other hand, PAs found in LH are a group of hepatotoxic otonecine-type PAs with clivorine as a representative [ 11 ]. These substances may lead to the deactivation of cellular antioxidant enzymes and resultant oxidative stress [ 12 ]. Both otonecine-type PAs and polysaccharides are water-soluble and can be co-administered orally in water extract of LH in Chinese medical practice.…”