The Possible Protective Effect of Vorinostat Versus Metformin on a Rat Model of New-Onset Post Transplantation Diabetes: Histological, Immunohistochemical, and Biochemical Study | ||
| Ain Shams Medical Journal | ||
| Articles in Press, Accepted Manuscript, Available Online from 19 November 2025 PDF (33.27 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/asmj.2025.377846.1440 | ||
| Authors | ||
| Heba Fikry1; Lobna A Saleh2; Hadwa Ali Abd-Alkhalek3; Doaa R Sadek* 4 | ||
| 1Assistant professor, Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Address: Khalifa El-Maamon st, Abbasiya sq. Cairo, Egypt. Post Code : 11566 | ||
| 2Assistant professor, Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Assistant professor, Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Address: | ||
| 3Assistant professor, Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. | ||
| 4Assistant professor, Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Address: Khalifa El-Maamon st, Abbasiya sq. Cairo, Egypt. | ||
| Abstract | ||
| Background: One of the most popular immunosuppressants used for organ transplants is tacrolimus. New-onset diabetes after transplantation (NODAT) occurs when patient develops diabetes mellitus (DM) following a solid organ transplant. The impact of metformin on newly-onset diabetes following transplantation due to immunosuppressant treatment is not well understood, even though it is a first-line medicine for type 2 DM. Aim: To demonstrate the possible protective effects of vorinostat versus metformin against diabetic nephropathy in the tacrolimus-induced NODAT rat model. Materials and Methods: Forty-two adult male rats were randomly divided into six groups: negative control, vorinostat, metformin, NODAT rat model (induced by tacrolimus), NODAT + vorinostat, and NODAT + metformin. High dose of tacrolimus was given by subcutaneous injection for four weeks to develop NODAT. Vorinostat and metformin were concomitantly given with tacrolimus to rats of group 5 and 6 for 4 weeks. At the end of the experiment after 4weeks, blood samples were collected to measure kidney function. kidneys were subjected to histological, immunohistochemical, histomorphometric examination as well as measuring of oxidative stress markers. Results: in NODAT group, there was a discernible increase in the weight of the kidneys, which was successfully halted with administration of vorinostat. H&E, Masson trichrome, PAS, and Gordon & Sweets’ silver impregnation staining revealed statistically significant kidney injuries. Rats given tacrolimus as the only treatment had significantly higher levels of caspase-3 reaction in their proximal tubular cells. It was significantly reduced in rats treated with vorinostat as compared to the metformin-treated rats. The most important finding of this study was that vorinostat and metformin treatment caused different glucose-lowering effects. Metformin improved this condition, but not to the degree seen in vorinostat. Conclusion: Vorinostat was more effective than metformin in protecting rat kidneys against tacrolimus-induced NODAT rat model. Vorinostat controlled diabetic kidney damage by increasing antioxidant capacity, decreasing oxidative damage, and decreasing apoptosis. Therefore, Vorinostat showed a double-edged sword: it prevented kidney damage and improved biochemical outcomes. | ||
| Keywords | ||
| Caspase-3; histological; kidney; metformin; MDA; NODAT; rat; vorinostat | ||
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