Effects of hirudotherapy on liver functions, lipid profile, and insulin sensitivity in rats with metabolic syndrome
Bilden A, Kocak S, Yildiz HT, Cakir F, Kahraman M, Cicek M (2026) · BMC Complementary Medicine and Therapies · n=24
Study Profile
- Design
- experimental preclinical animal study in 24 male Wistar rats randomly assigned to four groups: Control (n=6), Metabolic Syndrome (METS, n=6), METS + 4-week hirudotherapy (n=6), and METS + 8-week hirudotherapy (n=6); METS induced via modified high-fat and fructose-enriched diet; outcomes evaluated for liver enzymes, lipid profile, hemodynamics, glucose metabolism (OGTT, AUC), and liver histopathology (Kirsehir Ahi Evran University Faculty of Medicine, Turkiye)
- Sample size (n)
- 24
- Intervention
- Hirudotherapy (medicinal leech therapy) applied to METS-induced rats for either 4 or 8 weeks; outcomes assessed via serum biochemistry (AST, ALT, TG, LDL/HDL cholesterol), blood pressure measurements, oral glucose tolerance testing, and terminal liver histopathology
- Comparator
- Within-study comparison of METS+hirudotherapy arms versus METS alone and healthy Control; no randomized clinical comparator
- Primary endpoint
- Composite assessment of liver enzymes (AST, ALT), lipid profile (TG, LDL, HDL), systolic/diastolic blood pressure, glucose metabolism (OGTT, AUC), and liver histopathology (steatosis, sinusoidal dilatation, hydropic degeneration)
- Primary result
- Hirudotherapy produced significant reductions in AST and ALT (p<0.05), indicating hepatoprotective activity; TG levels increased in METS while LDL cholesterol showed partial improvement and HDL cholesterol remained unchanged; systolic blood pressure significantly decreased in hirudotherapy-treated groups (no significant change in diastolic or heart rate); OGTT and AUC analyses revealed improved glucose tolerance and reduced hyperglycemia (p<0.05); histopathology showed improvements in steatosis, sinusoidal dilatation, and hydropic degeneration; differences in pellet consumption suggested potential appetite-regulatory effect
- Follow-up duration
- 4-week and 8-week treatment periods plus terminal analysis
- PMID
- 41507963
Key Findings
- First preclinical study to systematically evaluate hirudotherapy for metabolic syndrome (METS) in a rat model
- Significant hepatoprotective effect (reduced AST/ALT) — translational signal for non-alcoholic fatty liver disease and metabolic-syndrome liver involvement
- Significant systolic blood pressure reduction in hirudotherapy-treated arms
- Improved glucose tolerance and reduced hyperglycemia (p<0.05) — translational signal for insulin resistance and prediabetes
- Histopathological improvements in liver steatosis, sinusoidal dilatation, and hydropic degeneration
Limitations
- Preclinical animal study only - no direct clinical translation
- Small sample size (n=6 per arm) limits statistical power
- Single high-fat-fructose diet METS model - generalizability to other METS phenotypes untested
- Specific bioactive compounds responsible for the metabolic effects not identified
- No comparison to standard pharmacological METS therapies (metformin, statins, antihypertensives)
Clinical Implications
Bilden 2026 provides preclinical signal that medicinal leech therapy improves multiple metabolic syndrome parameters in a rat model. For US clinicians, the trial does not change current clinical practice but adds to the growing preclinical literature on hirudotherapy for cardiometabolic indications. Translation to clinical practice would require IND-enabling studies, dose-finding pilots, and adequately powered RCTs against guideline-recommended METS therapies (lifestyle, metformin, statins, antihypertensives). The trial is included to document the active preclinical translational research program in cardiometabolic hirudotherapy and is hypothesis-generating only.