TOXICOLOGICAL EVALUATION OF NOVEL ANTIDIABETIC COMPOUNDS IN PRECLINICAL MODELS

Abstract

This preclinical experiment evaluated the toxicological safety profile of three novel antidiabetic compounds- known as Compound A, Compound B and Compound C- on a mixture of in vivo, in vitro and biochemical experiments.  In a repeated-dose study in mouse models, all the drugs were well tolerated with no mortality or severe adverse clinical outcomes.  The histopathological analysis showed that there were moderate to mild changes in hepatic and renal tissues, and Compound A showed the least organ-specific toxicity.  Dose-dependent and reversible changes in liver enzymes (ALT, AST) and renal biomarkers (creatinine, BUN) were found to be evident in high-dose cohorts of Compound C, but these changes corroborated the protective effects that Compound A and B could exert through oxidative stress biomarkers (malondialdehyde, reduced glutathione).  In vitro cytotoxicity studies on pancreatic -cell lines have shown a high cell viability (>85) to be obtained at therapeutic concentrations, although the tests of genotoxicity (Ames test and the micronucleus assay) have not shown any mutagenic prospect of the three drugs.  This paper demonstrates that the new antidiabetic chemicals possess an acceptable overall toxicological profile, with Compound A being the least toxic.  These findings support the further pharmacological development and confirm the shift to more advanced preclinical and first clinical trials.