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Therapeutic effect of dithiophenolato chitosan nanocomposites against carbon tetrachloride-induced hepatotoxicity in rats

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Abstract

Our previous study showed that dithiophenolate (DTP) and its chitosan nanoparticles (DTP-CSNPs) have abilities to bind with DNA helixes. So in this study, their lethal doses (LD50) and therapeutic roles against rat liver injuries induced by carbon tetrachloride (CCl4) were evaluated. The study focused on the determination of the markers of oxidative stress (OS) and apoptosis and compare the results with those of cisplatin treatment. The results revealed that LD50 values of DTP and DTP-CSNPs are 2187.5 and 1462.5 mg/kg, respectively. Treatment with DPT and DPT-CSNPs after CCl4 administration reduced liver injuries, induced by CCl4, and improved liver functions and architecture through the reduction of OS and apoptosis. Where the oxidant marker was decreased with elevations of antioxidant markers. Also, there was an elevation in Bcl-2 value, with decreases in caspase-8, Bax, and Bax/Bcl-2 ratio. DPT-CSNPs treatment gave preferable results than those treated with DPT. Moreover, DTP and DPT-CSNPs treatment gave better results than cisplatin treatment. The administration of healthy rats with low doses of DTP and DTP-CSNPs for 14 days had no effect. Otherwise, the study on HepG2 cell line showed that DTP and DPT-CSNPs inhibited cell growth by arresting cells in the G2/M phase and inducing cell death. In conclusion, DTP and DTP-CSNPs have antiapoptotic and anti-oxidative stress toward hepatotoxicity induced by CCl4. Moreover, DTP and DTP-CSNPs have anticancer activity against the HepG2 cell line. Generally, DTP-CSNPs are more effective than DTP. So, they can be used in the pharmacological fields, especially DTP-CSNPs.

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Acknowledgements

The authors thank Dr. Kamel R. Shoueir (Institute of Nanoscience & Nanotechnology, Kafrelsheikh University, Egypt) for his participation in the preparation of the studied complexes in the form of nanoparticles. Also, the authors thank Dr. Ahmed Alaa Abdelazis (Alexandria University, Faculty of Medicine) for his participation in the histological examination of the liver.

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Authors and Affiliations

  1. Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, 21511, Egypt

    Nadia Z. Shaban, Ahmed M. Aboelsaad, Doaa Awad & Shaymaa A. Abdulmalek

  2. Chemistry Department, Faculty of Science, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt

    Shaban Y. Shaban

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  1. Nadia Z. Shaban
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Contributions

Nadia Z. Shaban suggested this study, designed and organized and participated in the sequence arrangement, wrote and reviewed and approved the manuscript, and agreed to be accountable for all aspects of the work by ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Ahmed M. Aboelsaad participated in the suggestion of this study, participated in its design, carried out the experimental part in vitro and in vivo, performed the statistical analysis and drew the figures, and was a major contributor in writing and reviewing the manuscript. Doaa Awad participated in the statistical analysis. Shaymaa A. Abdulmalek participated in the supervision of the experiments in vitro. Shaban Y. Shaban participated in the supervision of the preparation of the studied complexes, read, and approved the final manuscript.

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Correspondence to Nadia Z. Shaban.

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HepG2 cell lines and all animal methodology were done following the Institutional Animal Care and Use Committee (IACUC) and approved via the Committee for Animal Care and Use in Alexandria University (ethical approval reference number: AU 042008 15 3 01).

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Highlights

1. DTP-CSNPs have antiproliferative activities and arrested HepG2 cells at the G2/M phase.

2. LD50 values of DTP and DTP-CSNPs are about 2187.5 and 1462.5 mg/kg, respectively.

3. DTP and DTP-CSNPs showed antiapoptotic effects against CCl4-induced hepatotoxicity.

4. Both compounds have antioxidant activities as GSH due to the presence of SH groups.

5. Treatment with DTP and DTP-CSNPs improved hepato- and nephrotoxicity.

6. DTP-CSNPs has a potent therapeutic effect than DTP and both are better than cisplatin.

7. Treatment with DTP-CSNPs gave better results than cisplatin treatment.

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Shaban, .Z., Aboelsaad, A.M., Awad, D. et al. Therapeutic effect of dithiophenolato chitosan nanocomposites against carbon tetrachloride-induced hepatotoxicity in rats. Environ Sci Pollut Res 29, 8487–8502 (2022). https://doi.org/10.1007/s11356-021-15834-x

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