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 â¼25 µg/kg and â¼50 µg/kg b.w may be considered as No Observed Adverse Effect Level (NOAEL) for intravenous and oral administration of TSA respectively.