Repeated dose toxicity studies of Trichostatin A in Swiss albino mice through oral and intravenous route of administration with special emphasis on genotoxicity

Abstract

Intravenous and oral 14 d repeated dose toxicity studies of Trichostatin A (TSA) were carried out in Swiss albino mice using low, intermediate, and high doses. Intravenous doses were 10, 25, and 50 μg/kg b.w while the oral doses were 20, 50, and 100 μg/kg b.w. Respective control groups of mice were administered phosphate buffered saline (vehicle only) for 14 consecutive days. All external morphological, hematological, biochemical, urine, histopathological, food intake in addition to body weight and vital organ weight were recorded. During the study no mortality in any animal was observed in either treatment routes. There were no significant changes in morphology, food intake, hematology, biochemical, urine analysis, organ weight. Animals treated high dose of TSA intravenously (50 μg/kg b.w) and orally (100 μg/kg b.w) had enlarged, congested, and discolored kidneys which were statistically significant. Histopathological studies had shown statistically significant degenerated glomerulus in high dose of intravenous and orally treated animals and degenerated tubule were found in orally treated animals. Genotoxicity was evaluated using micronucleus frequency at 14 and 21 d after treatment and chromosomal aberration at 21 d after treatment. Micronucleaus assay and chromosomal assay however did not show any significant changes at any doses and administration routes. Therefore, this study concludes that dose ∼25 µg/kg and ∼50 µg/kg b.w may be considered as No Observed Adverse Effect Level (NOAEL) for intravenous and oral administration of TSA respectively.

Keywords:

• Intravenous
• oral
• biochemical
• histopathological
• haematological
• micronucleaus assay
• chromosomal aberration assay
• NOAEL

Acknowledgements

The authors thank the Director, INMAS sincerely for his continuous support and encouragement during the work.

Disclosure statement

All the authors declare that they have no established conflicting financial interest or personal relationship that may have influenced the research presented in this paper.

Data availability statement

The author confirms that the data supporting the finding of the study are available within the article and no additional source of data are required.

Additional information

Funding

The work was supported by a DRDO, Govt of India research grant INM-313 to PKA.