Vol.:(0123456789) 1 3 Neurotoxicity Research https://doi.org/10.1007/s12640-020-00300-2 ORIGINAL ARTICLE Possible Role of Kaempferol in Reversing Oxidative Damage, Infammation, and Apoptosis‑Mediated Cortical Injury Following Cadmium Exposure Ashraf Al‑Brakati 1  · Alaa Jameel A. Albarakati 2  · Maha S. Lokman 3,4  · Abdulrahman Theyab 5  · Mohammad Algahtani 6  · Salah Menshawi 6  · Ohoud D. AlAmri 7  · Naif E. Al omairi 8  · Ehab A. Essawy 9  · Rami B. Kassab 4,10  · Ahmed E. Abdel Moneim 4 Received: 10 August 2020 / Revised: 15 October 2020 / Accepted: 18 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract Cadmium (Cd) is a heavy metal of considerable toxicity, inducing a number of hazardous efects to humans and animals including neurotoxicity. This experiment was aimed to investigate the potential efect of kaempferol (KPF) against Cd-induced cortical injury. Thirty-two adult Sprague-Dawley rats were divided equally into four groups. The control rats intraperito- neally (i.p.) injected with physiological saline (0.9% NaCl), the cadmium chloride (CdCl 2 )-treated rats were i.p. injected with 4.5 mg/kg of CdCl 2 , the KPF-treated rats were orally gavaged with 50 mg/kg of KPF, and the KPF + CdCl 2 -treated rats were administered orally 50 mg/kg of KPF 120 min before receiving i.p. injection of 4.5 mg/kg CdCl 2 . CdCl 2 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, CdCl 2 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, CdCl 2 mediated infammatory events in the corti- cal 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 CdCl 2 . However, KPF pretreatment restored signifcantly the examined markers to be near the normal values. Hence, the obtained data provide evidences that KPF pretreatment has the protective efect to preserve the cortical tissues in CdCl 2 -exposed rats by restrain- ing oxidative stress, infammatory response, apoptosis, neurochemical modulation, and improving the histological changes. Keywords Kaempferol · Cadmium · Oxidative stress · Infammation · Monoamines · Acetylcholinesterase * Maha S. Lokman ms.hussein@psau.edu.sa 1 Department of Human Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia 2 Surgery Department, College of Medicine, Al-Qunfudah Branch, Umm Al-Qura University, Makkah, Saudi Arabia 3 Biology Department, College of Science and Humanities, Prince Sattam bin Abdul Aziz University, Alkharj, Saudi Arabia 4 Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt 5 Department of Laboratory Medicine, Security Forces Hospital, Mecca, Saudi Arabia 6 Department of Laboratory Medicine, The Comprehensive Specialized Clinics of Security Forces, Jeddah, Saudi Arabia 7 Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia 8 Department of Internal Medicine, College of Medicine, Taif University, Taif, Saudi Arabia 9 Department of Chemistry, Faculty of Science, Helwan University, Cairo, Egypt 10 Department of Biology, Faculty of Science and Arts, Al Baha University, Almakhwah, Al Baha, Saudi Arabia