Abstract
Background:
Wound healing is a complex physiological process involving hemostasis, inflammation, proliferation, and remodeling. Erythrocyte and platelet parameters, along with erythrocyte morphology including poikilocytosis, are valuable indicators of systemic responses to injury and therapeutic interventions. Manuka honey and chlorine dioxide (ClO2) are known for their antimicrobial and reparative properties, yet systemic hematological effects following topical application remain poorly characterized.

Aim:
This study aimed to evaluate systemic hematological responses in Wistar rats with surgically induced wounds following the topical application of manuka honey and ClO2, compared with gentamicin treatment and untreated controls, focusing on erythrocyte and platelet parameters and poikilocytosis.

Methods:
Sixty Wistar rats were randomly assigned to four groups: control (C, n=15), gentamicin (AB, n=15), manuka honey (MH, n=14), and chlorine dioxide (ClO2, n=15). Under full anesthesia, a 4 cm abdominal incision was surgically induced in all rats, followed by twice-daily topical treatment for 14 days. On day 14, peripheral blood samples were collected for hematological analysis, including red blood cell count (RBC), hemoglobin concentration (HGB), hematocrit (HCT), platelet count (PLT), plateletcrit (PCT), and poikilocytosis. Statistical comparisons were performed using the Kruskal-Wallis test, significance was set at p < 0.05.

Results:
Most hematological parameters remained within expected physiological ranges. Significant intergroup differences were observed for HGB, HCT and PLT. Post hoc Dunn comparisons showed that HGB was significantly higher in the AB group than in the C group (p=0.011), ClO2 (p=0.015), and MH (p=0.006) groups. HCT was significantly higher in the AB group compared with the C (p=0.037), ClO2 (p=0.015), and MH (p=0.011) groups. PLT was significantly higher in the ClO2 group compared with the C (p=0.041), AB (p=0.019) and MH (p=0.014) groups. Poikilocytosis was minimal in all groups, primarily absent to mild, with the most frequent forms being anulocytes and stomatocytes.

Conclusion:
At the evaluated endpoint, topical application of manuka honey and ClO2 did not reveal marked systemic hematological disturbances in Wistar rats with surgical wounds. ClO2 had the most pronounced effect on platelet parameters among the tested treatments. Minimal poikilocytosis further supports the relative hematological stability observed at the evaluated endpoint. These findings provide valuable insights into systemic responses to topical treatments applied to surgically induced wounds and support further studies incorporating leukocyte profiling, complementary hematological, immunological, and histopathological assessments.

Key words: Chlorine dioxide; Hematology; Manuka honey; Wound.