Protective Effect of Ambroxol against Paraquat-induced Pulmonary Fibrosis in Rats

Abstract

Objective To evaluate the possible therapeutic effect of ambroxol on pulmonary fibrosis induced by paraquat. Methods Adult male Sprague-Dawley rats (n =144, 200-250 g) were divided into four groups (Control, Ambroxol, Paraquat, and Paraquat+Ambroxol group) and sacrificed on day 1, 3, 5, 7, 14 and 28. Several significant oxidant stress markers (MDA, SOD and GSH-PX), MPO activity, cytokines (TNF-α, MCP-1, TGF-β1, MMP-2 and TIMP-1), total inflammatory cell count, hydroxyproline content, collagen I and III mRNA were analyzed. Results In Paraquat group, the MDA, MPO activity, hydroxyproline contents, the mRNA expression of TNF-α, MCP-1, TGF-β1, MMP-2, TIMP-1, collagen I, collagen III and the number of total inflammatory cells were up-regulated in lung tissue, but SOD and GSH-PX activity were down-regulated in lung tissue compared with Control group (p<0.05). In paraquat+ambroxol group, the MDA, MPO activity, hydroxyproline content, the mRNA expression of TNF-α, MCP-1, TGF-β1, MMP-2, TIMP-1 collagen I, collagen III and the number of total inflammatory cells were significantly decreased, while the SOD and GSH-PX activities in lung tissue were increased compared with Paraquat group (p<0.05). Histological examination of paraquat-treated rats showed lung injury with interstitial edema and widespread inflammatory cell infiltration in the alveolar space and septum, as well as pulmonary fibrosis. Ambroxol could markedly reduce such damage in lung tissue and prevent pulmonary fibrosis. Conclusion The results of this study indicated that ambroxol could reduce lung damage and prevent pulmonary fibrosis induced by paraquat.

Suppressive effects of the expectorant drug ambroxol hydrochloride on quartz-induced lung inflammation in F344 rats

“…Ambroxol administration has been reported to suppress the lipopolysaccharide-induced production of TNF-α, IL-1β, interleukin-6 (IL-6), superoxide, hydrogen peroxide, and nitric oxide derived from rat macrophages in vitro 23 . In rats with paraquat-induced lung fibrosis, the protective effect of ambroxol was histologically prominent and presumably mediated by its free radical scavenging and antioxidant activity 8 . The results of our study of the effects of ambroxol treatment on quartz-induced lung inflammation in rats are consistent with these observations.…”

“…It has also been demonstrated that two intravenous injections of 20 mg/kg ambroxol hydrochloride with a 6-h interval stimulated synthesis and secretion of exogenous pulmonary surfactant in the lungs and exerted a protective effect in SD rats against pneumonia induced by Pseudomonas aeruginosa 7 . Paraquat-induced lung damage was reduced by a 28-day consecutive administration of ambroxol at a dose of 35 mg/kg 8 . However, there have been no studies that have explored potential effects of ambroxol on instilled particle-induced lung inflammation in F344 rats.…”

The dose of cyclophosphamide for treating paraquat-induced rat lung injury

“…Lee et al [21] showed that IL-6 plasma levels were not elevated at 6 and 12 hours in a PQ-intoxicated rat model (50 mg/kg), although a different study showed that IL-6 levels in lung tissues were higher 1 day after PQ injection in a rat model (18 mg/kg) [25]. Although some studies have suggested that TNF-α is involved in PQ-induced lung injury [26,27], the time sequence and peak of TNF-α have yet to be revealed in PQ intoxication. Therefore, it is necessary to investigate time sequence variation in IL-6 and TNF-α in PQ intoxication further.…”

Intoxications au paraquat en Guyane française : utilisation persistante lors de comportements suicidaires en outre-mer

“…L'ultime recours en cas de fibrose pulmonaire grave reste la greffe pulmonaire mais son succès est aléa-toire [2,12]. Certaines publications font état de travaux en cours sur d'autres molécules, comme des antioxydants tels que la N-acétylcystéine, la vitamine C, l'acide salicylique, la défé-roxamine ou encore l'ambroxol [15,[19][20][21].…”