The impact of N-acetylcysteine on early periods of tendon healing: histopathologic, immunohistochemical, and biomechanical analysis in a rat model

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Abstract
This study aimed to evaluate the early effects of N-acetylcysteine, which has antioxidant, inflame-modulatory, and cytoprotective properties, on tendon healing. Thirty-five male Wistar Hannover rats were divided into five groups: first-week treatment (Group 1T), first-week control (Group 1C), third-week treatment (Group 3T), third-week control (Group 3C), and native tendons (Group N). Bilateral Achilles tenotomy was performed on all rats except Group N. After tenotomy, 150 mg/kg N-acetylcysteine was administered daily intraperitoneally to treatment groups, while isotonic saline was given to the control groups. Tendons were evaluated histopathologically, immunohistochemically, and biomechanically after sacrifice in the first and third weeks. No significant differences were observed in the first week (p > 0.05). Movin and Bonar scores (lower scores reflect improved histologic healing) were significantly lower in Group 3T than in Group 3C (p = 0.002). Collagen type-I/type-III ratios were higher in Group 3T compared to Group 3C (p = 0.001). Fmax (N) values were similar across Group 3T, Group 3C, and Group N (p = 0.772). However, cross-sectional areas (mm2) were significantly smaller in Group 3T than in Group 3C (p = 0.001), with the smallest areas observed in native tendons. Thus, tensile strength (MPa, load per unit area) and toughness (J/103 mm3, energy absorbed per unit volume) were significantly higher in Group 3T than in Group 3C (p = 0.001). N-acetylcysteine supplied some improved results on early markers of tendon healing. Although our findings support the potential of NAC as a therapeutic adjunct in tendon injuries, further studies are needed to evaluate the long-term effects and underlying mechanisms.

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