Acute and Sub-Acute Toxicity Assessment of Cardionogen-1 in C57BL/6J Mice

Cardionogen-1 (CDNG-1), a small molecule inhibitor of Wnt/β-catenin signaling, has shown promising pharmacological effects, in vitro but its in vivo safety remains unclear. This study assessed both acute and sub-acute toxicity of CDNG-1 in C57BL/6J mice of both sexes. For acute toxicity testing, the mice were intraperitoneally (i.p.) administered with a single dose of 5, 50, 300, or 2000 μM/kg body weight (b.w.) CDNG-1 and observed for 14 days. In the sub-acute study, mice were treated with 250, 500, or 1000 μM/kg b.w., i.p., CDNG-1 once daily for 28 days. The animals were monitored for toxic signs and mortality throughout the experiment. Various biochemical and hematological parameters were analyzed along with histopathological examination. The acute toxicity study showed that the LD₅₀ value of CDNG-1 is more than 2000 μM/kg. In both the acute and sub-acute toxicity studies, the male and female mice showed no clinical signs of toxicity or death. Body weight changes and vital organ weights of the CDNG-1-treated mice remained comparable to control. Hematological and biochemical parameters, including liver and kidney markers, showed no significant alterations. Although a significant change in the hemoglobin level was observed in female mice treated with 250 and 500 μM/kg b.w., CDNG-1 for 28 days, it was within the normal range and not considered toxic. Gross morphological analysis and histopathological examination of the liver, kidney, and heart further revealed intact tissue architecture without marked pathology. Therefore, these findings suggest that CDNG-1 is well tolerated and did not induce any adverse effects in C57BL/6J adult male and female mice under both acute and repeated-dose exposure.