A Study to Evaluate the Anti-Inflammatory Effect of Doxycycline in Albino Rats

ABSTRACT Background: Inflammation is a coordinated biological response to infection, tissue injury and other harmful stimuli. Although antimicrobial therapy treats the infectious trigger, inflammation itself may contribute substantially to tissue injury and clinical manifestations. Tetracyclines have attracted interest as potential host-directed anti-inflammatory agents because their biological effects extend beyond antimicrobial activity, including inhibition of matrix metalloproteinases (MMPs) and modulation of inflammatory mediators. The present experimental study evaluated the anti-inflammatory activity of doxycycline in a standardized carrageenan-induced paw edema model in adult albino rats. Methods: Twenty-four inbred adult albino rats of either sex, weighing 200–250 g, were allocated to four groups of six animals each. The control group received distilled water; the standard group received aspirin 200 mg/kg orally; and the two test groups received doxycycline 0.05 mg/kg and 0.1 mg/kg orally, respectively. One hour after treatment, acute inflammation was induced by subplantar injection of 0.1 mL of 1% carrageenan into the right hind paw. Paw volume was measured by plethysmography at baseline and at 1, 2 and 4 hours after carrageenan administration. Edema was expressed as the difference between post-carrageenan paw volume and baseline volume. Group differences were analyzed using one-way analysis of variance (ANOVA), with statistical significance defined as p<0.05; the source study reports an overall p<0.001. Results: Baseline paw volumes were comparable across groups at 1.16±0.25 mL. Carrageenan produced a progressive increase in paw edema in the control group, reaching an edema volume of 1.41±0.20 mL at 4 hours. At 4 hours, mean edema volume was 0.38±0.13 mL with aspirin, 0.51±0.16 mL with doxycycline 0.05 mg/kg and 0.48±0.09 mL with doxycycline 0.1 mg/kg. The reported percentage inhibition of edema at 4 hours was 73% for aspirin, 64% for doxycycline 0.05 mg/kg and 66% for doxycycline 0.1 mg/kg. Thus, both doxycycline doses demonstrated substantial anti-inflammatory activity, with the 0.1 mg/kg dose showing a slightly greater effect than the 0.05 mg/kg dose, although neither matched aspirin in this experiment. Conclusion: Doxycycline demonstrated measurable anti-inflammatory activity in the carrageenan-induced paw edema model at both tested doses. The findings support the concept that doxycycline possesses pharmacological effects beyond antimicrobial activity. However, the study is small, uses a single acute animal model, and reports limited statistical detail; therefore, the results should be interpreted as experimental evidence rather than as evidence for replacing NSAIDs in clinical practice. Further dose-ranging, mechanistic and translational studies are required. Keywords: doxycycline; inflammation; carrageenan; paw edema; matrix metalloproteinases; tetracyclines; aspirin; anti-inflammatory activity; albino rats.