Study of the potential protective efficacy of lactoferrin on indomethacin-induced gastric fundic mucosal injury in rats.

Gastric mucosal injury is one of the most prevalent gastrointestinal disorders. Lactoferrin, a multifunctional glycoprotein, is recognized for its potent antioxidant and anti-inflammatory properties. This study investigated the protective and therapeutic potential of lactoferrin against indomethacin-induced gastric fundic mucosal injury. Forty-two male rats were randomized into four groups: the control group (Group I), which was further subdivided into subgroup IA (which received normal saline) and subgroup IB (which received a daily oral dose of 300 mg/kg Lf); the indomethacin-only group (Group II), which received a single oral dose of indomethacin (60 mg/kg) and was then subdivided into subgroup IIA (euthanized 6 h post-induction) and subgroup IIB (euthanized 21 days post-induction); the lactoferrin-pretreated group (Group III), which received 300 mg/kg/day Lf for 21 days, received a single oral dose of indomethacin (60 mg/kg) on the 22nd day, and was then subdivided into subgroup IIIA (euthanized 6 h post-induction) and subgroup IIIB (euthanized 21 days post-induction); and the lactoferrin-treated group (Group IV), which received a single oral dose of indomethacin (60 mg/kg) and then received a daily oral dose of Lf at 300 mg/kg for 21 days. Gastric tissues were processed for histomorphometric and biochemical assessments. In the indomethacin-only group, subgroup IIA showed extensive hemorrhagic lesions and mucosal erosions, while subgroup IIB exhibited deeper ulcerations. The lactoferrin-pretreated group (Group III) showed a significant reduction in the extent and severity of mucosal erosions at both time points, with the 21-day recovery (subgroup IIIB) showing superior outcomes. Notably, prophylactic lactoferrin administration in Group III demonstrated higher efficacy in preserving mucosal integrity compared to the post-injury therapeutic regimen of Group IV. In conclusion, our findings suggest that Lactoferrin may exert a gastroprotective effect associated with the modulation of antioxidant, anti-inflammatory, and anti-apoptotic pathways. Moreover, prophylactic administration of lactoferrin demonstrated potential in mitigating acute mucosal damage and supporting tissue repair within this model.