Attenuation of Hyperoxia-induced Lung Injury in Rats by Adrenomedullin

Abstract

Oxidative stress and inflammation are involved in the pathogenesis of acute lung injury (ALI). Adrenomedullin (AM) is an endogenous peptide with anti-inflammatory and antioxidant properties. This study investigated that whether AM treatment may ameliorate hyperoxia-induced ALI in rats via inhibition of oxidative stress and inflammation. Rats were randomized to receive continuous intravenous infusion of AM or saline through a microosmotic pump, and then ALI was induced by exposing the animals in sealed cages >95% oxygen for 72 h. Exposure to hyperoxia caused lung injury as increased infiltration of inflammatory cells and disruption of lung architecture. AM administration markedly improved these changes. Additionally, AM administration significantly increased glutathione peroxidase and superoxide dismutase activities. Meanwhile, hyperoxia-induced increase of lipid hydroperoxide level was markedly reduced by AM treatment. Moreover, nuclear factor-kappa B-DNA-binding activity, and production of the inflammatory mediators interleukin-6, keratinocyte-derived chemokine, and matrix metalloproteinase 9, were significantly inhibited by AM treatment. AM ameliorates hyperoxia-induced ALI in rats by suppression of oxidative stress and inflammation.

Improvement of ventilation-induced lung injury in a rodent model by inhibition of inhibitory κB kinase

“…4,17 IL-6 is known as an important inflammatory indicator. 4,23 Increased levels of IL-6 have been consistently shown to correlate with aggravated lung injury. 4,22 IL-6 deletion using an IL-6Yspecific inactivating antibody or IL-6 geneYdeficient mice results in ameliorated lung injury following ischemic acute kidney injury or bilateral nephrectomy.…”

“…3 A growing body of evidence suggests that suppression of the NF-JB pathway by non-specific NF-JB inhibitors can dampen lung injury. 3,4 NF-JB sequestered in cytoplasm in an unstimulated state through interaction with its inhibitory proteins, Inhibitory JB (IJB). Phosphorylation of IJB results in its ubiquitination and degradation, while NF-JB is activated and translocated from the cytoplasm to the nucleus.…”

Regulation of myofibroblast differentiation and bleomycin-induced pulmonary fibrosis by adrenomedullin

“…Previous studies have demonstrated that ADM administration or gene delivery attenuates hypertension, cardiac remodeling, and renal injury in various animal models (3,9,41,42,44,54,62,63). In the lung, adrenomedullin attenuates acute lung injury in animal models (24,37,57), attenuates pulmonary hypertension in animal models and in humans (34,38,39), and regulates allergen-induced airway hyperresponsiveness in mice (67). However, regulation of myofibroblast function and pulmonary fibrosis by ADM signaling has been poorly investigated, and this is the focus of this study.…”

Upregulation of Shh and Ptc1 in hyperoxia‑induced acute lung injury in neonatal rats

“…Neonatal rodents are recognized to be tolerant to high levels of hyperoxia compared to adults. Recently, hyperoxia-induced pulmonary molecular changes in the neonatal rat BPD model have been described; murine alveolar development begins on P4d and saccular division is completed by P14d (13). During the 2-week period of hyperoxia in this study, the survival rate of the hyperoxiaexposed rats was reduced to 73%, and the lung weight was reduced to a lesser extent than the body weight.…”

“…Under deep pentobarbital anesthesia (50 mg/kg, intraperitoneal), a midline incision was made through the sternum and abdomen, and whole-lung tissue was obtained. Lung and body weights were recorded at the time of sacrifice (12)(13)(14).…”