N-Acetyl-Cysteine: Protective Agent or Promoter of Gastric Damage?

Abstract

N-acetyl-cysteine (NAC), when given orally, has been shown to prevent gastric damage induced by ethanol, but when administered intraperitoneally, it appears to potentiate such damage. In an effort to resolve these seemingly discordant findings, fasted rats (six per group) received 1 ml of saline or 20% NAC orally or intraperitoneally (ip). Two hours or 15 min later, they received 1 ml of 100% ethanol orally. At sacrifice 5 min later, rats receiving oral pretreatment with 20% NAC at both 15 and 120 min prior to ethanol exposure demonstrated a significant reduction in the magnitude of gastric injury when compared with saline controls. In contrast, actual promotion of ethanol damage was noted when NAC was given intraperitoneally, but was more pronounced when NAC was administered 15 min prior to exposing the mucosa to 100% ethanol. In all animals receiving intraperitoneal NAC, large amounts of peritoneal fluid (4-6 ml/rat) were recovered at the time of sacrifice, most of which occurred within 15 min of NAC administration; these more pronounced peritoneal effects at 15 min after NAC correlated with the more severe injury from ethanol at this time period compared to 120 min after intraperitoneal NAC. Saline controls had no peritoneal fluid. Mucosal glutathione (GSH) levels generally paralleled these results in that a significant decrease in tissue GSH occurred at 15 min following intraperitoneal NAC when compared with controls; at 120 min after intraperitoneal NAC, GSH levels were similar to control values. Additional experiments demonstrated that within 15 min following NAC administration, systemic blood pressure dropped by approximately 20% and basically remained unchanged over the next 2 hr; intraperitoneal saline had no sustained adverse effects on blood pressure. It was concluded that the inability of NAC to prevent ethanol injury when given intraperitoneally in contrast to orally is related to the drop in blood pressure secondary to NAC's peritoneal irritant effects, which presumably altered gastric mucosal blood flow, thus obivating its ability to prevent ethanol damage under these conditions. Furthermore, the decreased levels in mucosal GSH following the hypotension induced by intraperitoneal NAC suggest that perturbations in GSH metabolism may also have contributed to the decreased resistance to ethanol injury.

Modulatory role of N-acetyl-cysteine on gastric mucosal lesions and some biochemical changes in Wistar rats subjected to cold restraint stress

“…This finding was supported by a study conducted by Yasmin et al (2022). Furthermore Lopez et al (1991) found that oral administration of NAC protected the gastric mucosa against ethanolinduced gastric injury…”

Protective effect of N-Acetylcysteine against ethanol-induced gastric ulcer: a pharmacological assessment in mice

“…Intra peritoneal administration of GSH protected gastric mucosa against stress induced mucosal ulcerations [ 32 ]. In addition, oral administration of NAC has been found to protect the gastric mucosa against ethanol-induced gastric injury [ 33 ]. While oral NAC administration protected against ulcer [ 34 ], other study showed that intra-peritoneal administration of NAC increased the amount of gastric mucosal lesions after ethanol application secondary to reduced gastric mucosal blood flow [ 35 ].…”

“…While oral NAC administration protected against ulcer [ 34 ], other study showed that intra-peritoneal administration of NAC increased the amount of gastric mucosal lesions after ethanol application secondary to reduced gastric mucosal blood flow [ 35 ]. Furthermore, NAC given intra-peritoneally in very high dose (1200 mg/kg) increased gastric injury [ 33 ]. The gastro-protective effect of oral NAC administration in the present study, which lowers mean ulcer size, may be due to the action against myeloperoxidase (MPO)/H 2 O 2 /Cl − system.…”