Role of macrophage bioenergetics in N-acetylcysteine-mediated mitigation of lung injury and oxidative stress induced by nitrogen mustard

Toxicol Appl Pharmacol. 2024 Mar 19:116908. doi: 10.1016/j.taap.2024.116908. Online ahead of print.ABSTRACTNitrogen mustard (NM) is a toxic vesicant that causes acute injury to the respiratory tract. This is accompanied by an accumulation of activated macrophages in the lung and oxidative stress which have been implicated in tissue injury. In these studies, we analyzed the effects of N-acetylcysteine (NAC), an inhibitor of oxidative stress and inflammation on NM-induced lung injury, macrophage activation and bioenergetics. Treatment of rats with NAC (150 mg/kg, i.p., daily) beginning 30 min after administration of NM (0.125 mg/kg, i.t.) reduced histopathologic alterations in the lung including alveolar interstitial thickening, blood vessel hemorrhage, fibrin deposition, alveolar inflammation, and bronchiolization of alveolar walls within 3 d of exposure; damage to the alveolar-epithelial barrier, measured by bronchoalveolar lavage fluid protein and cells, was also reduced by NAC, along with oxidative stress as measured by heme oxygenase and Ym-1 expression in the lung. Treatment of rats with NAC attenuated the accumulation of macrophages in the lung expressing proinflammatory genes including Ptgs2, Nos2, IL-6 and IL-12; macrophages expressing inducible nitric oxide synthase, cyclooxygenase-2 and tumor necrosis factor-α protein were also reduced in histologic sections. Conversely, NAC had no effect on macrophages expressing the anti-inflammatory proteins arginase-1 or mannose...

Source: Toxicology and Applied Pharmacology - March 21, 2024 Category: Toxicology Authors: Rama Malaviya Jaclynn Meshanni Vasanthi R Sunil Alessandro Venosa Changjiang Guo Elena V Abramova Kinal N Vayas Chenghui Jiang Jessica A Cervelli Andrew J Gow Jeffrey D Laskin Debra L Laskin Source Type: research