Crocin alleviates "short-term" Cadmium-induced brain and lung toxicities: investigation of key neuropeptides GLP-1 and spexin as biomarkers.

Abstract

Cadmium is a highly neurotoxic heavy metal that impacts the functions of several organs through stimulating excessive oxidative stress. Polyphenols were evidenced to mitigate heavy metal-induced neurotoxicity and pulmonary toxicity. Crocin (CN) is a carotenoid compound extracted from Crocus sativus L. This study explored the protective activities of CN against Cadmium chloride (CdCl₂)-induced neurotoxicity and lung injury. Thirty-two female albino Wistar rats, 6-8 weeks-old, were allocated into four groups: Negative control, CdCl₂-intoxicated rats (two successive intraperitoneal doses of 1 and 3 mg/kg body weight), CN group, and treated CdCl₂ rats with CN (50 mg/kg body weight, orally). Hanging-wire test was used to assess the muscular coordination. Biochemically, lipid peroxidation and glutathione (GSH) contents in the brain and lung homogenates, serum iron and phosphorus levels, serum Glucagon-like Peptide-1 (GLP-1) and spexin (SPX) levels were measured, along with histopathological investigation of cerebellar and pulmonary tissues. CdCl₂ rats demonstrated loss of neuromuscular coordination and imbalance in the hanging-wire test. Furthermore, CdCl₂ rats exhibited increased lipid peroxidation, GSH decline, disruption of iron and phosphorus levels, and reduction of GLP-1 and SPX levels. Concomitant treatment of CdCl₂-rats with CN, for two weeks, restored the muscular strength, mitigated oxidative stress, regulated iron and phosphorus levels, modulated GLP-1 and SPX, and ameliorated the histopathological features in the cerebellum and the lungs. We concluded that CN exerted neuroprotective and pulmonary protective potentials against CdCl₂-induced toxicity, and that GLP-1 and SPX could be regarded as biomarkers of heavy metals-associated neurotoxicity and lung toxicity.