Rasha M. Salama & Omyma Ibraheem Zedan
Peripheral nerve injury is frequently associated with incomplete functional recovery despite surgical intervention. Sitagliptin, a dipeptidyl peptidase-4 inhibitor, has shown anti-inflammatory, antioxidant, and anti-apoptotic qualities in a number of animal models. This study was designed to evaluate the potential neuroregenerative effect of sitagliptin following median nerve crush injury in rats. Forty-eight adult male albino rats were randomly assigned into eight groups, including sham-operated, sitagliptin-treated, median nerve injury, and median nerve injury treated with sitagliptin groups, evaluated at 7 and 28 days. Sitagliptin was orally administered at a dose of 10 mg/kg/day. Biochemical assessment included oxidative stress markers, antioxidant enzymes, inflammatory cytokines, and nerve growth factor. Hematoxylin and eosin and Masson's trichrome were used for the histological evaluation, while immunohistochemical analysis assessed GFAP, Nrf2, and BAX expression. Median nerve crush injury at 7 days (MNI-7 group) resulted in marked oxidative stress, inflammatory response, apoptosis, structural nerve disruption, and collagen deposition, accompanied by reduced nerve growth factor levels. While, MNI-28 group unambiguously illustrated some improvement in all measured parameters. Sitagliptin treatment significantly attenuated lipid peroxidation, restored antioxidant enzyme activity, reduced inflammatory markers, and increased nerve growth factor levels. Histological and immunohistochemical findings demonstrated improved nerve architecture, reduced fibrosis, decreased GFAP and BAX immunoreactivity, and enhanced Nrf2 expression, particularly with prolonged treatment. These findings indicate that sitagliptin promotes biochemical and structural recovery following median nerve crush injury, likely through its anti-inflammatory, antioxidant, and anti-apoptotic properties, pointing to a possible medicinal use in promoting peripheral nerve regeneration.
KEY WORDS: Peripheral nerve injury; Sitagliptin; Oxidative stress; GFAP; Nrf2; BAX.
SALAMA, R. M. & ZEDAN, O. I. Neuroregenerative impact of dipeptidyl peptidase IV inhibitor (sitagliptin) on median nerve injury in rats: Biochemical, histological, and immunohistochemical methodology. Int. J. Morphol., 44(1):258-275, 2026.
