Original Article

Reduction of oxidative stress in total knee arthroplasty using tourniquet with a novel pharmaceutical combination

¹ Department of Orthopaedics, Patras University Hospital, Patras 26504, Greece
² Department of Biology, University of Patras, Patras 26504, Greece
³ Department of Pharmacy, University of Patras, Patras 26504, Greece
⁴ Department of Medical Physics, School of Medicine, University of Patras, Patras 26504, Greece
⁵ School of Medicine, University of Patras, Patras 26504, Greece

^* Corresponding authors: irinitatani@gmail.com (I. Tatani); c.georgiou@upatras.gr (C.D. Georgiou); ecpanagi@upatras.gr (E. Panagiotopoulos)

Received: 13 May 2025
Accepted: 6 July 2025

Abstract

Introduction: Tourniquet use in total knee arthroplasty (TKA) can cause ischaemia-reperfusion (I-R) injury via oxidative stress. This study evaluated whether combined administration of the antioxidant N-acetylcysteine (NAC) and the iron-chelator Deferiprone can mitigate oxidative damage and improve clinical outcomes. Materials and methods: Twenty TKA patients were randomized into two groups, one group receiving NAC (600 mg, 6 h pre-op) and Deferiprone (1000 mg, 2 h pre-op) (intervention group) and the other group serving as placebo (control). Lipid hydroperoxides (LOOH) and protein malondialdehyde (PrMDA) were measured from quadriceps muscle tissue samples at 5 min (T1) and 40 min (T2) after tourniquet inflation, and 5 min after deflation (T3). Blood markers including serum ferritin, white blood cell (WBC) count, and polymorphonuclear neutrophils (PMNs) were assessed along with tissue PrMDA and LOOH as primary outcome measurements, while pain scores and knee flexion were recorded postoperatively as secondary outcome measurements. Results: LOOH levels were significantly lower in the intervention group at T2 and T3. PrMDA levels showed no significant differences. Ferritin levels rose by 69% in controls vs. 18% in the intervention group. WBC and PMNs normalized faster, with reduced pain and improved range of motion in the intervention group. Conclusion: The attenuation of LOOH elevation, the faster PMN deactivation, the inhibition of ferritin release from the cells along with the improved clinical outcomes suggest that combined NAC and Deferiprone administration may reduce tourniquet-related oxidative stress and inflammation, enhancing early recovery in TKA patients.