The possible impact of vitamin D3 on peripheral neuropathy induced by diabetes in a rat model / by Engie Samir El Sawaf (Teaching Assistant Pharmacology & Toxicology & Biochemistry department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt)

Supervision of Dr. Dalaal Moustafa Abdallah (Professor of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University), Dr. Samira Saleh Mostafa (Professor of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University), Dr. Hanan Salah El-Din El-Abhar (Professor & Head of Pharmacology, Toxicology & Biochemistry department, Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University in Egypt (FUE)

Thesis (M.Sc.)-Cairo university, Faculty of pharmacy, Department of Pharmacology and Toxicology, 2021.

Includes bibliographical references.

Vitamin D and rosuvastatin are two well-known drugs that mediate beneficial effects in type 2 diabetes (T2D) complications, however, their anti-neuropathic potential is still debatable. Hence, we studied the possible neurotherapeutic effect & the possible underling mechanisms. Additionally, evaluating the merit of their combination using a high fat fructose diet/streptozotocin (HFFD/STZ) T2D model. In addition to the control group, rats with T2D-associated neuropathy (6 weeks post STZ) were allocated into untreated and treated with vitamin D (cholecalciferol, 3500 IU/kg/week), rosuvastatin (10 mg/kg/day), or both. After 2 months of treatment, the therapeutic effect on small/large nerves was investigated using tail flick test, electrophysiological examination and histological evaluation, which documented that long-term use of vitamin D and/or rosuvastatin regenerated neuronal function and architecture of the sciatic nerve. These treatment regimens also decreased neuronal inflammation and apoptosis verified by inhibiting neuron content of TNF- and IL-18, as well as caspase-3 activity, while augmenting Bcl-2 content. On the molecular level, vitamin D and rosuvastatin abated the protein expression of NICD1, Wnt-10, β-catenin and TGF-β, while augmented the sciatic nerve content of SMAD7. These effects were associated with an upturn in the neuronal mitochondrial function (NRF-1, TFAM, mtDNA, and ATP). In conclusion, vitamin D and/or rosuvastatin abridged diabetes-induced neuropathy via turning off Notch1, Wnt-10/β-catenin and modulating TGF-β/SMAD7 signaling along with enhancing mitochondrial function, effects that lessened neuronal degeneration, demyelination and fibrosis.

Text in English, abstracts in English and Arabic.