Toxicological study of the indirubin derivative 7BIO

Indirubins represent a group of natural and synthetic products with significant bio-activities against numerous human cancer cell lines. Indirubins can be found in plants such as Isatis sp., Indigofera sp., and Polygonum sp., in recombinant bacteria, in mammalian urine, and in some marine mollusks such as Murex sp. [1,2]. Specifically, the halogenated derivative 7-bromo indirubin-3'-oxime (7BIO) has shown anticancer properties by causing cell death in several tumour cell lines [3,4] and may be a new therapeutic option for treatment-resistant tumour cells [5]. However, to the best of our knowledge, no study regarding the safety profile of 7BIO in vivo has been carried out till now. Thus, the aim of this study was to conduct a toxicity study of 7BIO in rodents.

Healthy Wistar male rats were daily administered (i.p) with either vehicle (Control), or 20 mg/kg BW (low dose), 50 mg/kg BW (medium dose), and 100 mg/kg BW (high dose) of 7BIO for 9 consecutive days. By the end of the treatment period, 1/6 and 3/6 animals deceased in the medium dose and high dose groups, respectively. Regarding the histopathology parameters, no treatment-related effects with regard to any of the toxicological biomarkers considered were observed in kidneys, testis, pancreas, spleen, stomach, and colon. However, granulomas were prominent throughout the peritoneal cavity in a dose-dependent manner; in the lungs, peribronchial fibrosis in both central bronchi and peripheral bronchioles were consistently noticed. Animals administered with high dose of 7BIO presented intense liver toxicity signs: intense macro- and microvesicular steatosis was prominent in 70% of hepatocytes in centrilobular and midzonal areas; apoptotic figures as well as extensive periportal necrosis and fibrosis were also evident. These results provide for the first time an insight in the in vivo toxicological properties of the anticancer agent 7BIO.

Acknowledgements: The technical assistance of Eirini Fragkiadaki and Panagiotis Kalliontzis is gratefully acknowledged. This work was performed with the support of the project NATPROT (No. 3207) funded by the Greek Secreteriat for Research and Technology and the action ARISTEIA II.

Keywords: Indirubin, 7BIO, toxicity, Wistar rats.

References:

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