Thymoquinone and geraniol alleviate cisplatin-induced neurotoxicity in rats through downregulating the p38 MAPK/STAT-1 pathway and oxidative stress

• Published in: Life sciences (1973) 2019-07, Vol.228, p.145-151
• Main Authors: Kandeil, Mohamed A., Mahmoud, Mohamed O., Abdel-Razik, Abdel-Razik H., Gomaa, Safaa B.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - toxicity; Antioxidants - therapeutic use; Apoptosis; Apoptosis - drug effects; Benzoquinones - therapeutic use; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain damage; Brain injury; Chemotherapy; Cisplatin; Cisplatin - toxicity; Dimethylaniline monooxygenase (N-oxide-forming); Down-Regulation - drug effects; Gelatinase B; Geraniol; GTP-binding protein; Kinases; Male; MAP kinase; Neurotoxicity; Neurotoxicity Syndromes - drug therapy; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - metabolism; Neurotoxicity Syndromes - pathology; Oxidative stress; Oxidative Stress - drug effects; p38 Mitogen-Activated Protein Kinases - metabolism; p53 Protein; Protein kinase; Rats; Rats, Wistar; Stat1 protein; STAT1 Transcription Factor - metabolism; Terpenes - therapeutic use; Thymoquinone
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2019.04.065

Cisplatin (CP) is a widely used broad-spectrum antineoplastic agent used to treat a variety of human malignancies. Neurotoxicity is clinically evident in patients who have undergone a full course of chemotherapy. The aim of this study was to investigate the possible protective effects of thymoquinone (TQ) and geraniol (Ger) against CP-induced neurotoxicity in rats. Forty male Wistar albino rats were allocated into four groups as follows: normal control, CP-induced neurotoxicity, CP + TQ and CP + Ger. Our results demonstrated that simultaneous treatment with either TQ or Ger and CP significantly abrogated oxidative stress and downregulated the apoptotic markers p38 mitogen-activated protein kinase (MAPK), STAT-1, p53, p21 and MMP9; FMO3, however, was insignificantly decreased. In addition to the biochemical results, we assessed the histopathological findings, which confirmed the protective effect of TQ and Ger against the brain damage induced by CP. The results of the present study indicate that simultaneous treatment with either TQ or Ger as natural antioxidants can provide protection against cisplatin-induced neurotoxicity in rats by attenuating oxidative stress and cell apoptosis.