Nifuroxazide Repurposing for Protection from Diabetes-induced Retinal Injury in Rats: Implication of JAK2/STAT3 Axis

Sunday, March 26, 2023

9:15 AM – 9:30 AM US EST

Room: Salon G

Presenting Author(s)

ME

Mohamed A. Eladl

Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
Sharjah, Sharjah, United Arab Emirates

Co-Author(s)

ME

Mohamed El-Sherbiny

Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia
Riyadh, Ar Riyad, Saudi Arabia
NA

Nada F. Abo El-Magd

Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
Mansoura, Ad Daqahliyah, Egypt
ME

Mohamed El-Shafey

Physiological Sciences Department, Fakeeh College for Medical Sciences, Saudi Arabia.Department of Anatomy and Embryology, faculty of Medicine, Mansoura University, Egypt
Jeddah, Makkah, Saudi Arabia
ME

Mamdouh Eldesoqui

Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia. Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Riyadah, Ar Riyad, Saudi Arabia
NA

Noorhan Al-Saleebi

Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia
Riyadah, Ar Riyad, Saudi Arabia
BA

Basim Alhomida

Department of Basic Medical Sciences, College of Medicine, AlMaarefa University,Riyadh , Saudi Arabia
Riyadah, Ar Riyad, Saudi Arabia
NE

Nehal M. Elsherbiny

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
Tabuk, Tabuk, Saudi Arabia

Abstract Body : Diabetic retinopathy (DR) is a prevailing microvascular complication of diabetes mellitus, representing the major cause of blindness among working age population worldwide. Inflammation is a crucial player in DR pathogenesis. JAK2/STAT3 axis is a pleotropic cascade that modulates diverse inflammatory events. Nifuroxazide (Nifu) is a commonly used oral antibiotic with reported JAK2/STAT3 inhibition activity. The present study investigated the potential protective effect of Nifu against diabetes-induced retinal injury. Effect of Nifu on JAK2/STAT3 axis and downstream inflammatory mediators has been also studied. Diabetes was induced in Sprague Dawley rats by single intraperitoneal injection of streptozotocin (50 mg/kg). Animals were assigned into four groups: normal, Nifu control, DM, and DM+Nifu. Nifu was orally administrated at 25 mg/kg/day for eight weeks. The effects of Nifu on JAK2/STAT3 axis proteins, inflammatory and anti-inflammatory factors, tight junction proteins, histological and ultrastructural alterations were evaluated using gene and protein analyses, histological studies, and transmission electron microscopy. Statistical significance among experimental groups was evaluated using one-way ANOVA test followed by Tukey’s post-hoc test. Nifu administration to diabetic rats attenuated histopathological and ultrastructural signs of retinal injury. Additionally, Nifu inhibited JAK2 and STAT3 phosphorylation, augmented the expression of STAT3 signalling inhibitor SOCS3, dampened the expression of transcription factor of inflammation NF-κB along with inflammatory cytokines TNF-α and IL-6, and restored the expression of anti-inflammatory cytokine IL-10 as well as tight junction protein occludin in diabetic retina. Collectively, the current study indicated that Nifu alleviated DR progression in diabetic rats, suggesting beneficial retino-protective effect. This can be attributed to blocking JAK2/STAT3 axis in retinal tissues with subsequent amelioration of inflammation.