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Article

Early Renoprotective Effect of Ruxolitinib in a Rat Model of Diabetic Nephropathy

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Department of Medical Pharmacology, Faculty of Medicine, Cairo University, Cairo 11559, Egypt
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Department of Pharmacology, Faculty of Pharmacy, Misr University for Science and Technology, Giza 12411, Egypt
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Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria 21526, Egypt
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Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
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Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
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Department of Biochemistry and Molecular Biology, Faculty of Medicine Cairo University, Cairo 11559, Egypt
*
Authors to whom correspondence should be addressed.
Academic Editors: Swayam Prakash Srivastava and Surya Pandey
Pharmaceuticals 2021, 14(7), 608; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070608
Received: 16 June 2021 / Accepted: 23 June 2021 / Published: 24 June 2021
(This article belongs to the Special Issue Advances in the Management of Diabetic Nephropathy)
Diabetic kidney disease (DKD) is still one of the unresolved major complications of diabetes mellitus, which leads ultimately to end-stage renal disease in both type 1 and type 2 diabetes patients. Available drugs that suppress the renin–angiotensin system have partially minimized the disease impact. Yet, there is an unmet need for new therapeutic interventions to protect the kidneys of diabetic patients. In DN, glomerular sclerosis and tubulointerstitial fibrosis are mediated through several pathways, of which JAK/STAT is a key one. The current study explored the potential renoprotective effect of the JAK1/JAK2 inhibitor ruxolitinib (at doses of 0.44, 2.2, and 4.4 mg·kg−1) compared to that of enalapril at a dose of 10 mg·kg−1, in a rat model of streptozotocin-induced diabetes mellitus over 8 weeks. The effect of ruxolitinib was assessed by determining urinary albumin/creatinine ratio, serum level of cystatin, and levels of TGF-β1, NF-κB, and TNF-α in renal tissue homogenates by biochemical assays, the glomerular sclerosis and tubulointerstitial fibrosis scores by histological analysis, and fibronectin, TGF-β1, and Vimentin levels by immunohistochemical staining with the respective antibodies. Our results revealed a significant early favorable effect of a two-week ruxolitinib treatment on the renal function, supported by a decline in the proinflammatory biomarkers of DKD. This pre-clinical study suggests that the renoprotective effect of ruxolitinib in the long term should be investigated in animals, as this drug may prove to be a potential option for the treatment of diabetic kidney disease. View Full-Text
Keywords: diabetic nephropathy; ruxolitinib; JAK inhibitors; glomerulosclerosis; tubulointerstitial fibrosis; rat model; TGF-β1; NF-κB; TNF-α diabetic nephropathy; ruxolitinib; JAK inhibitors; glomerulosclerosis; tubulointerstitial fibrosis; rat model; TGF-β1; NF-κB; TNF-α
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MDPI and ACS Style

El-Kady, M.M.; Naggar, R.A.; Guimei, M.; Talaat, I.M.; Shaker, O.G.; Saber-Ayad, M. Early Renoprotective Effect of Ruxolitinib in a Rat Model of Diabetic Nephropathy. Pharmaceuticals 2021, 14, 608. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070608

AMA Style

El-Kady MM, Naggar RA, Guimei M, Talaat IM, Shaker OG, Saber-Ayad M. Early Renoprotective Effect of Ruxolitinib in a Rat Model of Diabetic Nephropathy. Pharmaceuticals. 2021; 14(7):608. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070608

Chicago/Turabian Style

El-Kady, Mohamed M., Reham A. Naggar, Maha Guimei, Iman M. Talaat, Olfat G. Shaker, and Maha Saber-Ayad. 2021. "Early Renoprotective Effect of Ruxolitinib in a Rat Model of Diabetic Nephropathy" Pharmaceuticals 14, no. 7: 608. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070608

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