Ganoderma lucidum Prevents Cisplatin-Induced Nephrotoxicity through Inhibition of Epidermal Growth Factor Receptor Signaling and Autophagy-Mediated Apoptosis

• Published in: Oxidative medicine and cellular longevity Vol. 2020; no. 2020; pp. 1 - 13
• Main Authors: Mahran, Yasmen F., Hassan, Hanan M.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2020; Hindawi; Hindawi Limited
• Subjects: Acids; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Antioxidants; Apoptosis; Apoptosis - drug effects; Autophagy; Cancer; Caspase 3 - metabolism; Cell cycle; Chemotherapy; Cisplatin - administration & dosage; Cisplatin - adverse effects; Creatinine; Drug-Related Side Effects and Adverse Reactions - prevention & control; Epidermal growth factor; ErbB Receptors - metabolism; Flavonoids; HMGB1 Protein - genetics; HMGB1 Protein - metabolism; Humans; Kidney - metabolism; Kidney - pathology; Kidney Diseases - etiology; Kidney Diseases - prevention & control; Kidneys; Laboratory animals; Male; NF-kappa B - metabolism; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reishi; Signal Transduction
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2020/4932587

Background. Cisplatin (cis-diaminedichloroplatinum, CDDP) is a broad-spectrum antineoplastic agent. However, CDDP has been blamed for its nephrotoxicity, which is the main dose-limiting adverse effect. Ganoderma lucidum (GL), a medicinal mushroom, has antioxidant and inflammatory activities. Therefore, this study is aimed at finding out the potential nephroprotection of GL against CDDP-induced nephrotoxicity in rats and the possible molecular mechanisms including the EGFR downstream signaling, apoptosis, and autophagy. Methods. Rats were given GL (500 mg/kg) for 10 days and a single injection of CDDP (12 mg/kg, i.p). Results. Nephrotoxicity was evidenced by a significant increase in renal indices and oxidative stress markers. Additionally, CDDP showed a plethora of inflammatory and apoptotic responses as evidenced by a profound increase of HMGB-1, NF-κB, and caspase-3 expressions, whereas administration of GL significantly improved all these indices as well as the histopathological insults. Renal expression of EGFR showed a similar trend after GL administration. Furthermore, activation of autophagy protein, LC3 II, was found to be involved in GL-mediated nephroprotection correlated with the downregulation of apoptotic signaling, caspase-3 and terminal deoxynucleotidyl transferase (TDT) renal expressions. Conclusion. These results suggest that GL might have improved CDDP-induced nephrotoxicity through antioxidant, anti-inflammatory, and autophagy-mediated apoptosis mechanisms and that inhibition of EGFR signaling might be involved in nephroprotection.