Abrogation of bleomycin-induced lung fibrosis by nitric oxide synthase inhibitor, aminoguanidine in mice

Cannabinoid CB1 receptor overactivity contributes to the pathogenesis of idiopathic pulmonary fibrosis

“…In agreement with previous studies, we observed increased expression and activity of iNOS in lung tissue with both experimental and clinical PF (11,62). Nos2 -/-mice displayed lower levels of fibrosis than WT mice after bleomycin challenge ( Figure 5), in agreement with published findings (11,15); this also suggested that pharmacological inhibition of iNOS has therapeutic benefit in PF (14,15). Our finding that combined inhibition of CB 1 R and iNOS results in greater antifibrotic efficacy than equivalent inhibition of CB 1 R alone confirms this notion, and it also indicates that iNOS signals through targets not engaged by CB 1 R.…”

“…Furthermore, iNOS inhibitors have antifibrotic activity in animal models of PF (14,15), making iNOS a viable therapeutic target for PF.…”

Protection of bleomycin-induced fibrosis and inflammation by taurine

“…Results of Giri et al demonstrate that in mice, aminoguanidine, a specific inhibitor of iNOS, minimized bleomycin-induced fibrosis at both the biochemical and morphological levels [34]. bleomycin itself can produce superoxide anion (O − 2 ) and hydroxyl radicals which enhances the possibility of peroxynitrite formation, a potent oxidant formed from superoxide and NO.…”

Mechanisms and interventions in peritoneal fibrosis

“…Aminoguanidine also inactivates inducible nitric oxygen synthase, thereby giving it the ability to reduce vascular proliferation by modulating the expression of growth factors [28]. Beneficial effects of aminoguanidine on peritoneal microcirculation and tissue remodeling were demonstrated in a rat model of PD [29]; however, a clinical trial on aminoguanidine was terminated for safety reasons.…”