Exposure to Gynura Plants Causes Liver Damage in Rats and Liver Cells

Jim Crocker
17th August, 2024

Exposure to Gynura Plants Causes Liver Damage in Rats and Liver Cells

Image Source: Chris F (photographer)

Key Findings

  • The study by the Shandong Center for Disease Control and Prevention found that Gynura japonica causes significant liver damage in rats
  • Exposure to G. japonica led to liver cell death through apoptosis, involving changes in mitochondrial function and increased caspase-3 activity
  • The research highlights the need for public awareness and accurate identification of herbal remedies to prevent toxic exposure
Gynura japonica (Thunb.) Juel, a herb commonly used in traditional medicine, has been associated with significant liver toxicity. Often confused with non-toxic herbs like Tu-San-Qi (Sedum aizoon L.) and San-Qi (Panax notoginseng L.), G. japonica contains pyrrolizidine alkaloids (PAs), which are known to cause hepatic sinusoidal obstruction syndrome (HSOS) in over 50% of cases[1]. Despite its widespread use, the mechanisms underlying its hepatotoxicity have remained unclear. Recent research conducted by the Shandong Center for Disease Control and Prevention aimed to elucidate these mechanisms by investigating the toxic effects of a G. japonica decoction on liver and Buffalo rat liver (BRL) cells. In this study, researchers administered a G. japonica decoction to Sprague-Dawley rats to observe its impact on liver function and tissue damage. They used bioinformatics analysis to identify gene expression and pathways associated with hepatotoxicity. Advanced techniques like laser scanning confocal microscopy and flow cytometric annexin V/PI labeling assays were employed to observe apoptosis in BRL cells. Additionally, transmission electron microscopy and JC-1 staining were used to assess mitochondrial ultrastructure and membrane potential. The study also measured the expression of apoptosis-related proteins and caspase-3 activity using the bicinchoninic acid method and enzyme-linked immunosorbent assays. The findings revealed that exposure to G. japonica caused significant liver damage in rats, as evidenced by changes in body weight, liver histopathology, and serum liver function-related indices. Bioinformatics analysis suggested that the observed hepatotoxicity was linked to apoptotic signaling pathways, the positive regulation of programmed cell death, and responses to toxic substances. BRL cells exposed to the G. japonica decoction exhibited mid-to-late stage apoptosis and necrosis, along with notable alterations in mitochondrial morphology and membrane potential. Furthermore, there was an increase in the expression of cytochrome C (Cyt C) and pro-apoptotic proteins, a decrease in anti-apoptotic proteins, and elevated caspase-3 activity. These results align with previous studies that have highlighted the hepatotoxic potential of pyrrolizidine alkaloids found in G. japonica. For instance, it has been documented that G. japonica can lead to HSOS, characterized by obstruction of the hepatic sinusoids and central veins[2][3]. The study also supports earlier findings that pyrrole-protein adducts (PPAs), biomarkers for PA-induced HSOS, persist longer in the liver compared to serum, indicating prolonged hepatic exposure to toxins[2]. The current study advances our understanding by pinpointing the role of mitochondria-mediated apoptosis in G. japonica-induced hepatotoxicity. This mechanism involves the disruption of mitochondrial membrane potential and the release of Cyt C, which triggers a cascade of events leading to cell death. The elevation of caspase-3 activity further confirms the activation of the apoptotic pathway. These insights are crucial for developing targeted therapies and improving clinical management of PA-induced liver injuries. Moreover, this research underscores the importance of public awareness regarding the potential toxicity of herbal remedies. Misidentification of G. japonica with non-toxic herbs can lead to severe health consequences. Therefore, accurate identification and regulation of herbal products are essential to prevent inadvertent exposure to toxic compounds. In conclusion, the study conducted by the Shandong Center for Disease Control and Prevention provides a comprehensive understanding of the hepatotoxic mechanisms of G. japonica. By highlighting the role of mitochondria-mediated apoptosis, it offers a scientific foundation for clinical therapy and emphasizes the need for caution in the use of traditional herbal medicines.

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References

Main Study

1) Exposure to Gynura japonica (Thunb.) Juel plants induces hepatoxicity in rats and Buffalo rat liver cells.

Published 14th August, 2024

https://doi.org/10.1016/j.jep.2024.118692


Related Studies

2) The long persistence of pyrrolizidine alkaloid-derived pyrrole-protein adducts in vivo: Kinetic study following multiple exposures of a pyrrolizidine alkaloid containing extract of Gynura japonica.

https://doi.org/10.1016/j.toxlet.2020.01.021


3) Sinusoidal obstruction syndrome.

https://doi.org/10.1016/j.clinre.2020.03.019



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