Anti-apoptotic and anti-oxidant effects of systemic uridine treatment in an experimental model of sciatic nerve injury

Abstract

AIM:To investigate the anti-apoptotic and anti-oxidant effects of systemic uridine treatment in a rat model of sciatic nerve injury.MATERIAL and METHODS: Thirty-two adult male rats were equally randomized to Sham, Control, U100, and U500 groups. Sham rats received a sham operation by exposing the right sciatic nerve without transection, while those in the Control, U100, and U500 groups underwent right sciatic nerve transection followed by immediate primary anostomosis. Sham and Control groups received saline (0.9% NaCl) injections intraperitoneally (i.p.), while U100 and U500 groups received 100 mg/kg and 500 mg/kg uridine injections (i.p.), respectively, once a day for 7 days after the surgery. Rats in all the groups were sacrificed on the eighth day; sciatic nerve samples were analyzed for apoptosis by Western Blotting and for oxidation parameters including myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS:Uridine treatment at the dose of 500 mg/kg significantly decreased as apoptosis determined by Caspase-3/Actin ratio and exhibited significant anti-oxidant effects as determined by decreased levels of MPO and MDA as well as increased levels of SOD, GPx, and CAT compared to controls. Uridine at 100 mg/kg was only found to decrease the Caspase-3/Actin ratio, although it significantly decreased MDA and increased CAT levels compared to controls. CONCLUSION:Treatment with uridine reduces apoptosis and oxidation in a rat model of sciatic nerve injury dose-dependently. Thus, uridine may be beneficial in peripheral nerve regeneration by exhibiting anti-apoptotic and anti-oxidant effects.

Uridine and its role in metabolic diseases, tumors, and neurodegenerative diseases

“…Animal studies also demonstrated a dose-dependent decrease by uridine of apoptotic markers Caspase-3, oxidative markers myeloperoxidase (MPO) and malondialdehyde (MDA) in sciatic nerve tissue of rats with sciatic nerve injury. Mechanistically, uridine serves as a precursor for the synthesis of cytidine-5′-diphosphocholine (CDP-choline), a rate-limiting endogenous intermediate in phospholipid synthesis, which is necessary for nerve growth ( Khezri et al, 2021 ).…”

Modifications of Blood Molecular Components after Treatment with Low Ozone Concentrations

“…It has been demonstrated that 9H-purin-6-ol (also known as hypoxantine) tends to increase in hypoxic conditions [79]; since in our O 3 -treated samples hypoxantine decreased, we may assume that this effect could be due to the hyperoxygenation induced by O 3 . The uridine decrease may be related to its capability to stabilise energy metabolism as well as to its antioxidant capacity [80,81].…”