Mutagenicity and genotoxicity of isatin in mammalian cells in vivo

Abstract

Isatin (1H-indole-2,3-dione) is a synthetically versatile substrate used for the synthesis of heterocyclic compounds and as a raw material for drug synthesis. Isatin and its derivatives demonstrate anticonvulsant, antibacterial, antifungal, antiviral, and anticancer properties. We evaluated the genotoxic and mutagenic effects of acute (24h) and repeated (14d) exposure to isatin in vivo, using the comet assay and the micronucleus test. Three doses (50, 100, and 150mg/kgb.w.) were administered to mice via gavage. Doses were selected according to the LD(50) of isatin, estimated in a preliminary test to be 1g/kgb.w. To evaluate the results, parametric (ANOVA/Tukey) and non-parametric (Kruskal-Wallis/Dunn's post hoc test) tests were used, according to the nature of the data distribution. At all doses (50, 100 and 150mg/kgb.w.), after acute treatment with isatin, alterations in DNA migration (comet assay) were not observed and mutagenic effects were not seen (micronucleus test on peripheral blood cells). After repeated doses, only the highest dose of isatin (150mg/kgb.w.) induced alterations in the DNA that gave rise to micronuclei in the bone marrow and peripheral blood cells of the mice. Our results show that the mutagenic and genotoxic effects of isatin depend on dose and on period of exposure.

The role of natural indigo dye in alleviation of genotoxicity of sodium dithionite as a reducing agent

“…Studies by Jongen and Alink (1982) support the present results, they examined the mutagenic potential of two natural and seven synthetic commercial indigo products and they reported that natural products showed no mutagenicity in Salmonella typhimurium strains TA98 and TA100 but all of the synthetic products were found mutagenic. Also our results coincided with previous studies by Candido-Bacani et al (2011) which evaluated genotoxic and mutagenic effects of acute (24 h) and repeated (14 day) exposure to isatin as indigo precursor in vivo, and the results showed that the mutagenic and genotoxic effects of isatin depended on dose and-exposure period.…”

“…Natural Isatis plants, some indigo precursors and indirubin were also tested for their genotoxicity (Candido-Bacani et al 2011) and indirubin and its derivatives were found to possess low toxicity (Zhen et al 2007). In natural Isatis plants, some indigo precursors and indirubin known as red isomer of indigo were also tested for their genotoxicity (Candido-Bacani et al 2011) and indirubin and its derivatives were reported to possess low toxicity (Zhen et al 2007).…”

“…In natural Isatis plants, some indigo precursors and indirubin known as red isomer of indigo were also tested for their genotoxicity (Candido-Bacani et al 2011) and indirubin and its derivatives were reported to possess low toxicity (Zhen et al 2007). Various biological activities including antifebrile, anti-inflammatory, antiviral, antimicrobial, detoxifying purposes, restenosis and skin psoriasis (Hoessel et al 1999;Chiang et al 2013;Liau et al 2007) and antileukemic activity against myelocytic leukemia in Traditional Chinese Medicine (Hoessel et al 1999) have been reported for indirubin and its derivatives (Hoessel et al 1999).…”

“…Studies with respect to the monitoring the possible toxic effects of plant species are of great concern for public and environmental health for desired sustainable life comfort. According to previous reports, genotoxic effects of synthetic indigo and its dye solutions and natural indigo plants were examined (Candido-Bacani et al 2011;Calvo et al 2011) but to the best of our knowledge, no previous reports in relation to the genotoxic and cytotoxic effects of natural indigo dye solutions with sodium dithionite using human peripheral blood lymphocytes (PBLs) have been published.…”

Advances in Pharmacology of Isatin and its Derivatives: A Review

“…Isatin was first synthesized by Erdmann and Laurent in 1840 [2]. Isatin and triazole containing heterocyclic compounds are reported as a cure of lethal diseases [3].…”