Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg +2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro

• Published in: International journal of molecular sciences 2023-01, Vol.24 (1), p.772
• Main Authors: Wu, Zong-Han, Chiu, Chun-Hung, Chen, Chin-Chu, Chyau, Charng-Cherng, Cheng, Chi-Hung
• Format: Article
• Language: English
• Subjects: Animals; composition analysis; Cordyceps cicadae; Cyclosporine - toxicity; cyclosporine a; Endoplasmic Reticulum Chaperone BiP; endoplasmic reticulum stress; Immunosuppressive Agents - therapeutic use; Kidney - metabolism; Kidney Diseases - chemically induced; Kidney Diseases - drug therapy; Kidney Diseases - metabolism; liquid cultured mycelium; Magnesium - metabolism; Male; Protein Serine-Threonine Kinases - metabolism; Rats; Rats, Sprague-Dawley; renal injury
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24010772

Fruiting bodies of (CC) have been reported to have a therapeutic effect in chronic kidney disease. Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. However, little is known regarding potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity in vivo and in vitro. In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). At the end of the study on day 8, all rats were sacrificed, and the blood and kidneys retrieved. CsA-induced acute nephrotoxicity was evident by increased levels of blood urea nitrogen (BUN). Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity.