Celastrol and thymoquinone alleviate aluminum chloride-induced neurotoxicity: behavioral psychomotor performance, neurotransmitter level and oxidative-inflammatory burden in brain of rats

Abstract The exposure to metal aluminum such as aluminum chloride (AlCl3) induces inflammatory-oxidative reactions with progressive neurodegeneration in different brain regions in animal models. The current study was designed to assess the role of celastrol or thymoquinone (TQ) in alleviating AlCl3 induced behavioral psychomotor changes and oxidative-inflammatory burden in albino male rats. Four groups were used in this study, (i) vehicle control group, (ii) AlCL3 control group: rats received intraperitoneal injection (i.p.) of AlCl3 (10 mg/kg), (iii) AlCl3+TQ (10 mg/kg, i.p.) group and (iv) AlCl3+celastrol (1 mg/kg, i.p.) group. In general, all injections remained for 6 weeks. Behavioral psychomotor evaluation (open field test, rotarod test and forced Swimming test) were done to assess locomotor, motor coordination, anxiety-like behavior and depressive-like behavioral. Markers of oxidative stress, malondialdehyde (MDA), total antioxidant capacity (TAC) and catalase enzyme activity (CAT) and the proinflammatory mediators, tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) were measured in the rat brains. Neurotransmitters including acetylcholine (ACh), dopamine and serotonin in addition to acetylcholinesterase enzyme (AChE) level were measured in brain homogenates. Our results demonstrated that daily injection of TQ or celastrol significantly improved behavior psychomotor deficits, decreased AChE activity towards their normal levels. Tissue oxidative stress and proinflammatory markers were modulated by TQ and celastrol. These results concluded that TQ and celastrol have useful in alleviating AlCl3-induced neurotoxicity by their antioxidant and anti-inflammatory properties. Hence, they are looking promising for investigating their preventive effect in animal models of neurodegenerative diseases.

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