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Andrographolide protects against doxorubicin-and arsenic trioxide-induced toxicity in cardiomyocytes

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Abstract

Background

Andrographolide (AG) is a lactone diterpene with valuable biological activities. This in vitro study evaluated whether AG can protect cardiomyocytes under toxicities triggered with anti-cancer chemotherapeutic agents, doxorubicin (DOX) and arsenic trioxide (ATO).

Methods and results

H9C2 cells were pretreated with AG (0.5–10 µM) for 24 h and then exposed to DOX (1 μM) or ATO (35 μM) for another 24 h period. For determination of cell viability or cytotoxicity, MTT and lactate dehydrogenase (LDH) assay were used. Total oxidant and antioxidant capacities were estimated by determining hydroperoxides and ferric reducing antioxidant power (FRAP) levels. Real time-polymerase chain reaction was also used for quantitative evaluation of TLR4 gene expression. AG inhibited cardiomyocytes proliferation at the concentrations of more than 20 μM. However, it considerably enhanced cell viability and decreased cytotoxicity of DOX and ATO at the concentration range of 2.5–10 μM in MTT and LDH assays. AG significantly declined hydroperoxides concentration in ATO-treated cardiomyocytes and raised FRAP value in DOX- and ATO-treated cells. Furthermore, AG notably lessened TLR4 expression in H9C2 cells after exposure to DOX- and ATO.

Conclusion

In conclusion, these data presented that AG was able to reverse DOX- and ATO-induced cardiotoxicity in vitro. The cardiomyocyte protective activities of AG may be due to the decrease in TLR4 expression and total oxidant capacity and increase in total antioxidant capacity.

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Acknowledgements

This research was funded by Vice-Chancellery for Research and Technology of Isfahan University of Medical Sciences (Grant No. 299264).

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

    Leila Safaeian

  2. Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

    Fatemeh Shafiee

  3. Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

    Samira Haghighatnazar

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  1. Leila Safaeian
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Contributions

LS and FS contributed to the study conception and design. Material preparation, data collection and analysis was performed by SH. SH wrote the manuscript in consultation with LS and FS All authors discussed the results and approved the final form of the manuscript.

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Correspondence to Leila Safaeian.

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Safaeian, L., Shafiee, F. & Haghighatnazar, S. Andrographolide protects against doxorubicin-and arsenic trioxide-induced toxicity in cardiomyocytes. Mol Biol Rep 50, 389–397 (2023). https://doi.org/10.1007/s11033-022-08042-4

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