Acute toxicity assessment of a newly synthesized Benzimidazole derivative in male Wistar rats

Abstract

1,5-bis-(mercaptobenzimidazolyl) diethylene glycol (BBO1) is a newly synthesized benzimidazole derivative that has been characterized using comprehensive physicochemical analysis. Given the pharmacological potential of benzimidazole compounds and the lack of toxicological data for BBO1, this study investigated the acute toxicity of BBO1 in male Wistar rats. Male Wistar rats were randomly assigned to six groups and received a single intraperitoneal injection (ip) of BBO1 at doses of 250, 500, 750, 1000, and 1200 mg/kg, with one control group receiving vehicle. Animals were monitored daily for 14 days to assess mortality, food and water consumption, body weight (bw) changes, behavioral parameters, and oxidative stress biomarkers in brain tissues. The median lethal dose (LD₅₀) of BBO1 was determined to be 1071.4 mg/kg. High doses (750 and 1000 mg/kg) induced significant physiological alterations including initial weight loss and reduced food consumption. Behavioral assessments revealed decreased locomotor activity and increased anxiety- and depression-like behaviors in the high-dose groups. Biochemical analysis demonstrated significant increase in nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels in the prefrontal cortex (PFC) and hippocampus (HP), indicating oxidative stress (OS) induction. Lower doses (250 and 500 mg/kg) showed no significant effects. These results demonstrate that BBO1 exhibits dose-dependent acute toxicity with a threshold at 750 mg/kg, affecting physiological, behavioral, and neurochemical parameters. These findings provide essential safety data for future therapeutic applications and validate the experimental model for benzimidazole derivative toxicological assessment.