Possible Role of Kaempferol in Reversing Oxidative Damage, Inflammation, and Apoptosis-Mediated Cortical Injury Following Cadmium Exposure

Cadmium (Cd) is a heavy metal of considerable toxicity, inducing a number of hazardous effects to humans and animals including neurotoxicity. This experiment was aimed to investigate the potential effect of kaempferol (KPF) against Cd-induced cortical injury. Thirty-two adult Sprague-Dawley rats were divided equally into four groups. The control rats intraperitoneally (i.p.) injected with physiological saline (0.9% NaCl), the cadmium chloride (CdCl2)-treated rats were i.p. injected with 4.5 mg/kg of CdCl2, the KPF-treated rats were orally gavaged with 50 mg/kg of KPF, and the KPF + CdCl2-treated rats were administered orally 50 mg/kg of KPF 120 min before receiving i.p. injection of 4.5 mg/kg CdCl2. CdCl2 exposure for 30 days led to the accumulation of Cd in the cortical tissue, accompanied by a reduction in the content of monoamines and acetylcholinesterase activity. Additionally, CdCl2 induced a state of oxidative stress as evidenced by the elevation of lipid peroxidation and nitrate/nitrite levels, while glutathione content and the activities of glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase were decreased. Moreover, CdCl2 mediated inflammatory events in the cortical tissue through increasing tumor necrosis factor-alpha and interleukin-1 beta levels and upregulating the expression of inducible nitric oxide synthase. Furthermore, pro-apoptotic proteins (Bax and caspase-3) were elevated, while Bcl-2, the anti-apoptotic protein, was decreased. Also, histological alterations were observed obviously following CdCl2. However, KPF pretreatment restored significantly the examined markers to be near the normal values. Hence, the obtained data provide evidences that KPF pretreatment has the protective effect to preserve the cortical tissues in CdCl2-exposed rats by restraining oxidative stress, inflammatory response, apoptosis, neurochemical modulation, and improving the histological changes.