Thalidomide Modulates Oxidative Stress and Tubular Pathology in Renal Ischemia-Reperfusion in a Timing-Dependent Manner

Year 2025, Volume: 3 Issue: 3, 75 - 86, 15.01.2026

Onural Özhan , Ugur Cem Mete , Azibe Yıldız , Merve Durhan , Nigar Vardı , Yılmaz Çiğremiş , Ahmet Acet , Hakan Parlakpınar

https://doi.org/10.62425/rtpharma.1780199

Abstract

Background: Renal ischemia–reperfusion (IR) drives acute kidney injury through oxidative stress and inflammation. Thalidomide (TD), an immunomodulatory agent, may attenuate IR-related biochemical and structural damage.
Methods: Thirty-two female Wistar albino rats were randomized to four groups (n=8): Sham, IR, TD+IR (20 mg/kg i.p. 30 min before ischemia), and IR+TD (20 mg/kg i.p. immediately after 60-min ischemia). All animals underwent right nephrectomy, left renal ischemia (60 min), and 24-h reperfusion. Outcomes included serum blood urea nitrogen (BUN)/creatinine (CR)/albumin; renal malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT); and histopathology (tubular dilatation, epithelial shedding, intertubular congestion).
Results: IR increased BUN/CR versus Sham, while albumin was unchanged. TD+IR modestly lowered BUN/CR compared with IR, whereas IR+TD did not improve these indices at 24 h. MDA rose with IR and was reduced by TD+IR (vs IR), but not by IR+TD; CAT fell with IR and was highest in IR+TD, while GSH and SOD showed no significant group differences. Histologically, IR produced tubular epithelial shedding, dilatation, and intertubular congestion. TD+IR improved all parameters except epithelial shedding (vs IR), and IR+TD improved all except tubular dilatation; medullary congestion decreased in both TD groups, more prominently with IR+TD.
Conclusion: TD confers schedule-dependent renoprotection in renal IR. Pre-ischemic dosing more consistently preserves function and limits lipid peroxidation, whereas post-ischemic dosing better enhances CAT activity and alleviates medullary congestion. These data support TD as a context-dependent adjunct for peri-ischemic kidney protection.

Keywords

Thalidomide , Renal ischemia–reperfusion , Oxidative stress , Catalase , Tubular injury , Rat

Ethical Statement

Ethical approval (Protocol No. 2017/A-19) was granted by the Experimental Animal Ethics Committee of the Faculty of Medicine, İnönü University, on 23 March 2017.

Supporting Institution

Research Fund of the Inonu University

Project Number

TLO-2017-799

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