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Assessment of toxicity and genotoxic safety profile of novel fisetin ruthenium-p-cymene complex in mice

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Abstract

Throughout the last decades flavonoids have been considered as a powerful bioactive molecule. Complexation of these flavonoids with metal ions demonstrated the genesis of unique organometallic complexes which provide improved pharmacological and therapeutic activities. In this research, the fisetin ruthenium-p-cymene complex was synthesized and characterized via different analytical methods like UV–visible spectroscopy, Fourier-transform infrared spectroscopy, mass spectroscopy, and scanning electron microscope. The toxicological profile of the complex was evaluated by acute and sub-acute toxicity. Additionally, the mutagenic and genotoxic activity of the complex was assessed by Ames test, chromosomal aberration test, and micronucleus based assay in Swiss albino mice. The acute oral toxicity study exhibited the LD50 of the complex at 500 mg/kg and subsequently, the sub-acute doses were selected. In sub-acute toxicity study, the hematology and serum biochemistry of the 400 mg/kg group showed upregulated white blood cells, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, glucose and cholesterol. However, there was no treatment related alteration of hematological and serum biochemical parameters in the 50, 100, and 200 mg/kg group. In the histopathological analysis, the 50, 100, and 200 mg/kg groups were not associated with any toxicological alterations, whereas the 400 mg/kg group showed prominent toxicological incidences. Nevertheless, the treatment with fisetin ruthenium-p-cymene complex did not exhibit any mutagenic and genotoxic effect in Swiss albino mice. Thus, the safe dose of this novel organometallic complex was determined as 50, 100, and 200 mg/kg without any toxicological and genotoxic potential.

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Acknowledgements

The authors are grateful to the Department of Pharmacy, NSHM Knowledge Campus Kolkata-Group of Institution for their continuous support and encouragement throughout the experiment.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Pharmacy, NSHM Knowledge Campus Kolkata-Group of Institution, 124 B.L. Saha Road, Tara Park, Behala, 700053, West Bengal, India

    Ishita Seal, Sidhanta Sil, Abhijit Das & Souvik Roy

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  1. Ishita Seal
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  2. Sidhanta Sil
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by IS, SS, AD, and SR. The first draft of the manuscript was written by IS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Souvik Roy.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The animal experiment was approved by the Institutional Animal Ethics Committee and by the Animal Regulatory Body of the Government (Regd.No. 1458/PO/E/S/11/CPCSEA dated 12.05.2011).

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Seal, I., Sil, S., Das, A. et al. Assessment of toxicity and genotoxic safety profile of novel fisetin ruthenium-p-cymene complex in mice. Toxicol Res. 39, 213–229 (2023). https://doi.org/10.1007/s43188-022-00158-w

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  • DOI: https://doi.org/10.1007/s43188-022-00158-w

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