ABSTRACT
Neurotoxicity of Al is well established and linked to oxidative damage and neurodegeneration. This study investigated the protective role of genistein (Gen) and chickpea extract (CPE) against AlCl3-induced neurodegeneration. HPLC analysis revealed that biochanin A-7-O-ß-D-glucoside and biochanin A are the major components of the CPE. Gene expression of TNF-α, APP, BACE1, PSEN-2 and ER-ß were assessed in brain extract using RT-PCR. Also, NF-кB subunit P65 and COX-2 expression were evaluated by western blotting. The cholinergic function, histological examination and oxidative status were also estimated. The AlCl3 significantly up regulated the expression of the NF-кB subunit P65, COX-2, TNF- α, BACE1and APP while it significantly down regulated PSEN-2 and ER-ß expression. The activity of acetyl cholinesterase (AChE) and the oxidative stress parameters as well as the histological examination confirmed the deleterious effect of AlCl3. The administration of either CPE or Gen attenuated the expression of inflammatory cytokines, inhibited the amyloidogenesis and restored both the AChE activity and ER-ß expression. Gen and CPE also inhibited the oxidative stress and ameliorated the histological alterations. Accordingly, the present study provides an insight on the molecular role of Gen and CPE as protective agents against neuronal injury.
Subject(s)
Aluminum/toxicity , Cicer/chemistry , Genistein/administration & dosage , Neurodegenerative Diseases/prevention & control , Plant Extracts/administration & dosage , Protective Agents/administration & dosage , Animals , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Humans , Male , NF-kappa B/genetics , NF-kappa B/metabolism , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/metabolism , Oxidative Stress/drug effects , Plant Extracts/chemistry , Protective Agents/chemistry , Rats , Rats, Sprague-Dawley , Seeds/chemistry , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Gossypol displays anticancer behavior and anti-fertility in males. Male rats were treated with either gossypol acetic acid (GAA) or gossypol-iron complex (GIC). Serum alanine transaminase (ALT) activity elevated of GAA. However, GIC-treated animals showed a decrease in hepatic glutathione (GSH) content with increased malondialdehyde (MDA) content. Whereas, GSH-Px specific activity increased in GAA group. GAA and GIC induce significant increases in the hepatic NEFA with remarkable decrease in the total saturated fatty acids with a significant increase of PUFA. Lipid peroxidation is inhibited by gossypol, which shield lipids against oxidative damage. Phenols are oxidized to phenoxy radicals, which do not permit anti-oxidation due to resonance stabilization. GAA stimulate hydroxyl radicals (()OH) generation and DNA damage. GAA and GIC produce increase in lipid peroxidation as proved by a steep rise in thiobarbituric acid reactive species (TBARS). Controversy of specificity of TBARS towards compounds other than MDA was reported. If TBARS increased, more specific assay to be employed. Assay of lipid classes and fatty acids pattern, reveled the significance of the technique in assessment of lipid peroxidation in tissues. GAA and GIC were powerful inhibitors of lipid peroxidation and exhibit pro- and antioxidant behavior, with less toxicity of GIC.
