In an experimental animal study evaluating cadmium chloride-induced neurotoxicity, co-treatment with the lipid-lowering drug ezetimibe and the silk protein sericin significantly attenuated toxic neurological damage in adult Wistar rats. The researchers observed that cadmium exposure caused motor and cognitive deficits alongside elevated oxidative stress, neuroinflammation, and mitochondrial dysfunction in the brain. Treatment with ezetimibe and sericin, especially when administered in combination, produced pronounced protective effects that mitigated these impairments and counteracted the neurotoxicity induced by cadmium exposure.
Cadmium chloride exposure represents a global health concern linked to pathological neurotoxicity, marked oxidative stress, neuroinflammation, and the downregulation of the IGF-1R, GLP-1R, Nrf2, and HO-1 signaling pathway. Because interventions targeting this pathway may offer a strategy to lessen neurotoxic injury, the researchers investigated whether ezetimibe and sericin could protect against cadmium-induced damage. Ezetimibe is an established lipid-lowering agent, while sericin is a natural silk-derived protein recognized for its antioxidant and anti-inflammatory properties.
The investigation utilized seventy adult Wistar rats divided across experimental groups over a 28-day treatment period. The study design allocated animals to receive a control regimen, cadmium chloride at 5 mg/kg, cadmium chloride alongside ezetimibe at doses of 10 or 20 mg/kg, cadmium chloride with sericin at doses of 200 or 400 mg/kg, or concurrent combination therapy containing both compounds. Over the course of the 28-day protocol, the researchers conducted behavioral assessments, evaluating muscle coordination and cognitive dysfunction across the animal cohorts.
Following the 28-day dosing period, the animals were sacrificed on day 29 to enable biochemical and molecular analyses of hippocampal tissue. The authors evaluated markers of oxidative stress, measuring malondialdehyde, nitrite, and glutathione levels alongside acetylcholinesterase activity. They also quantified the neurochemicals serotonin and norepinephrine, assessed neuroinflammatory markers including tumor necrosis factor-alpha, interleukin-1beta, and nuclear factor kappa B, performed immunohistochemistry for glial fibrillary acidic protein, and measured mitochondrial complex-I activity and relevant protein expression.
The resulting data demonstrated that ezetimibe and sericin, particularly in the combined treatment group, improved motor behavior, maintained redox homeostasis, restored neurotransmitter levels, and decreased neuroinflammation. In addition to enhancing mitochondrial complex-I activity, the combination regimen restored the hippocampal protein expression of IGF-1R, GLP-1R, Nrf2, NF-κB, and HO-1. The authors concluded that ezetimibe and sericin, administered individually and in combination, counteract cadmium-induced neurotoxic effects in this experimental rat model.
Subject of Research: Ezetimibe and sericin attenuation of cadmium chloride-induced neurotoxicity in rats
Article Title: Combination of ezetimibe and sericin attenuates cadmium chloride-induced neurotoxicity in an experimental rat model by suppressing oxidative stress and neuroinflammation
Article References: Temgire, P., Navik, U., & Kumar, P. (2026). Combination of ezetimibe and sericin attenuates cadmium chloride-induced neurotoxicity in an experimental rat model by suppressing oxidative stress and neuroinflammation. Molecular Biology Reports, 53(1), Article 1906. https://doi.org/10.1007/s11033-026-12955-9
Image Credits: AI Generated
DOI: 10.1007/s11033-026-12955-9
Keywords: cadmium chloride, neurotoxicity, ezetimibe, sericin, oxidative stress, neuroinflammation, Wistar rats, hippocampus, Combination, attenuates, cadmium, chloride-induced
