Protective effects of N-acetylcysteine on gastric blood flow, nitric oxide bioavailability, oxidative stress, and hematological alterations in indomethacin-induced gastric ulceration in male Wistar rats

Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly indomethacin, are widely associated with gastrointestinal complications, including gastric ulceration, due to disruption of blood flow and mucosal defense mechanisms. N-Acetyl cysteine (NAC), a sulfur-containing compound with potent antioxidant and mucolytic properties, has demonstrated promising gastro protective effects. But, there is a dearth of information about gastric blood flow. Hence, this study investigated the dose-dependent gastroprotective and anti-ulcer effects of NAC compared with cimetidine in an indomethacin-induced gastric ulcer model in rats. A total of sixty (60) animals weighing between 150 and 180 g were divided into 2 separate sets for separate experiments, with thirty (30) animals in each set. The 2 separate sets are further divided into 5 sub-groups with 6 animals in each sub-group. The 2 (two sets of animals) undergo the same experimental treatment. Group I: Rats served as control received distilled water orally for 7 days before induction of ulcer with indomethacin (40 mg/kg) (ulcer control). Group II: Rats received cimetidine orally for 7 days (50 mg/kg) and indomethacin orally (40 mg/kg) on the last day. Group III, IV, V: Rats received NAC at doses of 100, 300, and 500 mg/kg, respectively, for 7 days orally before indomethacin orally (40 mg/kg) on the last day. One experimental set was used for the assessment of gastric blood flow and antioxidant parameters, while the second set was used for the evaluation of gastric mucus secretion. Following sacrifice by cervical dislocation, biological samples were collected for biochemical analyses. Significant increase in gastric blood flow was observed in all treated groups, with the most notable increases in the groups treated with 300 mg/kg and 500 mg/kg N-Acetyl cysteine, compared with the ulcer control. Sulfhydryl concentration significantly increase in all treated groups, particularly in the group receiving 500 mg/kg cysteine, relative to the ulcer control. The antioxidant enzyme SOD significantly increased across all treated groups, with the highest levels seen in the 500 mg/kg cysteine group, compared with the ulcer control. Mucus secretion significantly increase in all treated groups, especially in the 500 mg/kg cysteine group, relative to the control.