Primary throughput screening of protectants for hypothermic preservation of bioartificial liver in gel entrapped hepatocytes

Hypothermic preservation of bioartificial liver (BAL) has long been appreciated in BAL storage and transportation. However, the deterioration of cell activity during hypothermia/rewarming limits its clinical use and the complete prevention of hypothermia-induced hepatocyte injury has not been achieved. In this article, a miniaturized BAL that underwent three preservation stages (i.e. pre-incubation, hypothermia and rewarming) was applied as a hypothermic preservation model to locate the protection of several protective agents against hypothermia-induced cell injury. The agents, including vitamin E, schisandrin B, glycyrrhizic acid, N-acetyl-cysteine, ruthenium red, trehalose, anisodamine, fructose-1, 6-diphosphate, cyclosporin A and matrine (Mat), were found to exert their functions at different preservation stages, which were speculated to associate with the specific protection of each agent as well as the corresponding cell injuries at each stage. Such hypothesis was further strengthened by focusing on Mat, which only suppressed the hypothermia-induced injury through the inhibition of Ca(2+) overload at the rewarming stage, whereas its presence at the hypothermic stage excessively down-regulated the cytosolic free Ca(2+) and then aggravated cell death. The results indicate that the specific cell injury at each preservation stage requires a corresponding protective agent. However, the untimely misuse of the agents may inversely aggravate cell injury.

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Differential function of protective agents at each stage of the hypothermic preservation of hepatocytes

Dai

Meng

2011

Journal of Biochemistry

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Screening of herbal components for attenuating amiodarone-induced hepatotoxicity on gel-entrapped rat hepatocytes

Deng

Shen

Meng

2013

Drug and Chemical Toxicology

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Amiodarone (AMD) is a hepatotoxic drug that has been widely used as a class III antiarrhythmic drug. Because, to date, only a few kinds of protectants are able to reduce AMD hepatotoxicity, this article utilized gel-entrapped rat hepatocytes to screen effective protectants from a series of herbal compounds for their effects against AMD-induced toxicity. Herbal compounds, including matrine, silibinin, glycyrrhizic acid, schisandrin B, epigallocatechin gallate and anisodamine, were cotreated with AMD to assess their protective effect, whereas vitamin E, which has been shown to be protective in rats, was selected as a control. It was found that vitamin E, as with its function in rats, provided the best protection in gel-entrapped rat hepatocytes, whereas silibinin, a major component of silymarin, could largely reduce AMD-induced hepatotoxicity, performing a similar function as silymarin in rats. The results illustrated that gel-entrapped hepatocytes may reflect the protective effects of drugs and serve as a reliable model for screening hepatoprotectants. Moreover, matrine, a widely used monomer of the traditional Chinese medicine, Sophora flavescens, for treatment of arrhythmia, was evidenced to show some effective protections against AMD hepatotoxicity. Taken together, gel-entrapped rat hepatocytes may provide a platform for screening effective candidates from the herbal component library.

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Primary throughput screening of protectants for hypothermic preservation of bioartificial liver in gel entrapped hepatocytes

Cited by 2 publications

References 35 publications

Differential function of protective agents at each stage of the hypothermic preservation of hepatocytes

Differential function of protective agents at each stage of the hypothermic preservation of hepatocytes

Screening of herbal components for attenuating amiodarone-induced hepatotoxicity on gel-entrapped rat hepatocytes

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