Abstract
BACKGROUND: Nicotine is a behavioral stimulant that in high doses, through the neuro-inflammatory and oxidative stress pathway, can induce apoptosis and autophagy leading to cell death. Previous data indicate that crocin has neuroprotective properties. The aim of the current study is to investigate crocin's neuroprotective effects against nicotine-triggered neuro-inflammation, apoptosis, and autophagy in rat hippocampus. METHODS: Seventy adult male Wistar rats were divided into the following seven groups: Group one received normal saline (0.2 ml/rat), group two was treated with nicotine 10 mg/kg intraperitoneally, groups 3 to 6 were treated simultaneously with nicotine and crocin (10, 20, 40, and 80 mg/kg, intraperitoneally), group 7 was treated with crocin-alone (80 mg/kg, intraperitoneally). The period of the mentioned agent administration was 21 days. On the 22(nd) day, an open field test (OFT) was used for evaluation of anxiety and motor activity changes. Inflammatory and oxidative stress factors and also apoptosis and autophagy biomarkers were evaluated. RESULTS: All mentioned doses of crocin could decrease the nicotine-induced OFT behavioral changes. Crocin also could decrease levels of hippocampal TNF/TNF-α (tumor necrosis factor), IL1B/IL-1β (interleukin 1 beta), oxidized glutathione (GSSG), unphosphorylated and phosphorylated forms of JNK, BECN1 (beclin 1), BAX (BCL2 associated X, apoptosis regulator), and phosphorylated/inactive forms of BCL2 (BCL2 apoptosis regulator) in nicotine-dependent rats. Crocin treatments also caused increases in the reduced form of glutathione (GSH) content and activity of CAT (catalase) and mitochondrial complex enzymes in nicotine-addicted subjects. CONCLUSIONS: Crocin can modulate JNK-BCL2-BECN1 or JNK-BCL2-BAX signaling pathways and reduce neuronal oxidative stress, neuro-inflammation, and mitochondrial respiratory chain enzymes and exert neuroprotective effects against nicotine-induced neurodegeneration.