Dexpanthenol improved stem cells against cisplatin-induced kidney injury by inhibition of TNF-α, TGFβ-1, β-catenin, and fibronectin pathways

Khalifa El-Dawy; Nashwa Barakat; Hala Ali; Ikhlas A Sindi; Heba M Adly; Saleh A K Saleh

doi:10.1016/j.sjbs.2023.103773

Dexpanthenol improved stem cells against cisplatin-induced kidney injury by inhibition of TNF-α, TGFβ-1, β-catenin, and fibronectin pathways

Saudi J Biol Sci. 2023 Sep;30(9):103773. doi: 10.1016/j.sjbs.2023.103773. Epub 2023 Aug 9.

Authors

Khalifa El-Dawy¹, Nashwa Barakat², Hala Ali¹, Ikhlas A Sindi^{3

4}, Heba M Adly⁵, Saleh A K Saleh^{6

7}

Affiliations

¹ Biochemistry Dept., Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
² Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
³ Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia.
⁴ Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
⁵ Community Medicine and Pilgrims Healthcare Department, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
⁶ Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
⁷ Oncology Diagnostic Unit, Faculty of Medicine, Ain Shams University, Cairo 11435, Egypt.

Abstract

Introduction: Cisplatin interacts with DNA and induces an immunological response and reactive oxygen species, which are nephrotoxic mediators. Stem cells self-renew through symmetric divisions and can develop into other cell types due to their multipotency. Dexpanthenol has been proven to protect against renal injury.

Aim: This study aims to demonstrate that dexpanthenol could improve the effect of adipose-derived mesenchymal stem cells (ADMSC) against cisplatin-induced acute kidney injury.

Methods: Sixty male Sprague-Dawley rats were divided into 5 groups (N = 12): control, cisplatin, cisplatin & dexpanthenol, cisplatin & ADMSC, and cisplatin & dexpanthenol & ADMSCs. On the 5th day following cisplatin injection, half the rats in each group were sacrificed, and the other half were sacrificed on the 12th day. Histopathological examination, molecular studies (IL-6, Bcl2, TGFβ-1, Caspase-3, Fibronectin, and β-catenin), antioxidants (superoxide dismutase and catalase), and renal function were all investigated.

Results: In contrast to cisplatin group, the dexpanthenol and ADMSCs treatments significantly decreased renal function and oxidative stress while significantly enhancing antioxidants. Dexpanthenol improved stem cells by significantly down-regulating caspase-3, IL-6, TGF-β1, Fibronectin, and β-catenin and significantly up-regulating Bcl2 and CD34, which reversed the cisplatin effect.

Conclusion: Dexpanthenol enhanced ADMSCs' ability to protect against cisplatin-induced AKI by decreasing inflammation, apoptosis, and fibrosis.

Keywords: ADMSCs; Cisplatin; Dexpanthenol; Nephrotoxicity.