Investigation of the therapeutic effects of medicinal leech treatment on lower extremity ischemia-reperfusion injury
Unal K, Samur B, Sharif A, Ibrahimkhanli L, Yumusak N (2026) · Journal of Complementary & Integrative Medicine · n=18
Study Profile
- Design
- experimental preclinical animal study with 18 Wistar Albino rats randomly assigned to three groups: Sham (n=6), Ischemia/Reperfusion (I/R, n=6), and Medical Leech Treatment (MLT, n=6); I/R induced via femoral artery atraumatic vascular clamp; MLT applied to the gastrocnemius muscle region post-I/R; outcomes evaluated by histopathological scoring (edema, degeneration, necrosis, inflammation) and serum/tissue biochemistry (Faculty of Medicine, Gazi University, Ankara, and Faculty of Veterinary Medicine, Harran University, Turkiye)
- Sample size (n)
- 18
- Intervention
- Medicinal leech therapy applied to the gastrocnemius muscle region of each rat following femoral artery ischemia/reperfusion induction; outcomes assessed via histopathological scoring and biochemical analysis of IL-6, SOD, CGRP, NO, TNF-alpha, HIF-1alpha, IMA, GPx, CAT, and EDN-1 in serum and tissue
- Comparator
- Within-study comparison of MLT arm against I/R-alone and Sham arms
- Primary endpoint
- Composite histopathological score (edema, degeneration, necrosis, inflammation) and panel of inflammatory and oxidative-stress biomarkers
- Primary result
- Histopathological scores for edema, degeneration, necrosis, and inflammation were significantly lower in the MLT arm compared to the I/R group (p<0.001); biochemical analysis of inflammatory cytokines, oxidative stress markers, and vasoactive mediators (IL-6, SOD, CGRP, NO, TNF-alpha, HIF-1alpha, IMA, GPx, CAT, EDN-1) showed no statistically significant differences across groups; despite biochemical findings, the histopathological signal was robust and suggestive of clinical therapeutic effect
- Follow-up duration
- acute postoperative observation with terminal histopathological and biochemical analysis
- PMID
- 41607083
Key Findings
- Significant histopathological protection (edema, degeneration, necrosis, inflammation; p<0.001) from medicinal leech therapy in a rat I/R model
- Provides preclinical signal for limb-ischemia and reperfusion-injury indications beyond microsurgical flap salvage
- Adds Gazi University (Ankara) preclinical research program to the leech-ischemia-protection literature
- Histopathological signal robust despite absence of significant biochemical differences in inflammatory/oxidative markers
- Translational rationale for further investigation of MLT in acute and chronic limb ischemia
Limitations
- Preclinical animal study only - no direct clinical translation
- Small sample size (n=6 per arm) limits statistical power
- Inconsistency between histopathological signal and biochemical findings — mechanism unclear
- Specific bioactive compounds responsible for protective effect not identified
- Single I/R model (femoral artery clamp) - generalizability to other ischemia models untested
Clinical Implications
Unal 2026 provides preclinical signal that medicinal leech therapy protects against histopathological lower-extremity ischemia/reperfusion injury in a rat femoral artery model. For US clinicians, the trial does not change current clinical practice but adds to the growing preclinical literature supporting investigation of MLT for limb-ischemia indications (acute limb ischemia, reperfusion injury, chronic critical limb ischemia). The biochemical mechanism remains unclear and substantial mechanism work and clinical translation would be required. The trial is included to document the active preclinical translational research program and is hypothesis-generating only.