Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by <i>Cordyceps cicadae</i> Mycelia via Mg<sup>+2</sup> Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro
Fruiting bodies of <i>Cordyceps cicadae</i> (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 dev...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| author | Zong-Han Wu Chun-Hung Chiu Chin-Chu Chen Charng-Cherng Chyau Chi-Hung Cheng |
| author_facet | Zong-Han Wu Chun-Hung Chiu Chin-Chu Chen Charng-Cherng Chyau Chi-Hung Cheng |
| author_sort | Zong-Han Wu |
| collection | DOAJ |
| description | Fruiting bodies of <i>Cordyceps cicadae</i> (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. |
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| spelling | doaj.art-1044f838d6b4424cbad8282f97b5d3172023-11-16T15:38:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-0124177210.3390/ijms24010772Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by <i>Cordyceps cicadae</i> Mycelia via Mg<sup>+2</sup> Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In VitroZong-Han Wu0Chun-Hung Chiu1Chin-Chu Chen2Charng-Cherng Chyau3Chi-Hung Cheng4Research Institute of Biotechnology, Hungkuang University, Taichung 43302, TaiwanResearch Institute of Biotechnology, Hungkuang University, Taichung 43302, TaiwanGrape King Biotechnology Center, Longtan District, Taoyuan 325002, TaiwanResearch Institute of Biotechnology, Hungkuang University, Taichung 43302, TaiwanResearch Institute of Biotechnology, Hungkuang University, Taichung 43302, TaiwanFruiting bodies of <i>Cordyceps cicadae</i> (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.https://www.mdpi.com/1422-0067/24/1/772<i>Cordyceps cicadae</i>liquid cultured myceliumcyclosporine arenal injuryendoplasmic reticulum stresscomposition analysis |
| spellingShingle | Zong-Han Wu Chun-Hung Chiu Chin-Chu Chen Charng-Cherng Chyau Chi-Hung Cheng Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by <i>Cordyceps cicadae</i> Mycelia via Mg<sup>+2</sup> Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro International Journal of Molecular Sciences <i>Cordyceps cicadae</i> liquid cultured mycelium cyclosporine a renal injury endoplasmic reticulum stress composition analysis |
| title | Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by <i>Cordyceps cicadae</i> Mycelia via Mg<sup>+2</sup> Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro |
| title_full | Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by <i>Cordyceps cicadae</i> Mycelia via Mg<sup>+2</sup> Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro |
| title_fullStr | Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by <i>Cordyceps cicadae</i> Mycelia via Mg<sup>+2</sup> Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro |
| title_full_unstemmed | Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by <i>Cordyceps cicadae</i> Mycelia via Mg<sup>+2</sup> Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro |
| title_short | Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by <i>Cordyceps cicadae</i> Mycelia via Mg<sup>+2</sup> Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro |
| title_sort | amelioration of cyclosporine a induced acute nephrotoxicity by i cordyceps cicadae i mycelia via mg sup 2 sup reabsorption and the inhibition of grp78 ire1 chop pathway in vivo and in vitro |
| topic | <i>Cordyceps cicadae</i> liquid cultured mycelium cyclosporine a renal injury endoplasmic reticulum stress composition analysis |
| url | https://www.mdpi.com/1422-0067/24/1/772 |
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