2,2′-Azobis (2-Amidinopropane) Dihydrochloride Is a Useful Tool to Impair Lung Function in Rats

Abstract

Recently, several studies have reported that respiratory disease may be associated with an increased production of free radicals. In this context, 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH) is a free radical-generating compound widely used to mimic the oxidative stress state. We aimed to investigate whether AAPH can generate lung functional, inflammatory, histological and biochemical impairments in the lung. Wistar rats were divided into five groups and instilled with saline solution (714 μL/kg, CTRL group) or different amounts of AAPH (25, 50, 100, and 200 mg/kg, 714 μL/kg, AAPH groups). Seventy-two hours later the animals were anesthetized, paralyzed, intubated and static elastance (Est), viscoelastic component of elastance (ΔE), resistive (ΔP1) and viscoelastic (ΔP2) pressures were measured. Oxidative damage, inflammatory markers and lung morphometry were analyzed. ΔP1 and Est were significantly higher in AAPH100 and AAPH200 than in the other groups. The bronchoconstriction indexes were larger in AAPH groups than in CTRL. The area occupied by collagen and elastic fibers, polymorpho- and mononuclear cells, malondialdehyde and carbonyl groups levels were significantly higher in AAPH200 than in CTRL. In comparison to CTRL, AAPH200 showed significant decrease and increase in the activities of superoxide dismutase and catalase, respectively. AAPH augmented the release of pro-inflammatory cytokines IL-1β, IL-6 e TNF-α. Hence, exposure to AAPH caused significant inflammatory alterations and redox imbalance accompanied by altered lung mechanics and histology. Furthermore, we disclosed that exposure to AAPH may represent a useful in vivo tool to trigger lung lesions.

Increased selenium concentration in the synthesis of CdSe magic‐sized quantum dots affects how the brain responds to oxidative stress

“…However, AAPH did not increase lipid peroxidation (Figure 2B) or alter the SOD and CAT activities (Figure 3). Other studies have shown increases in lipid peroxidation and activities of the antioxidant enzymes SOD and CAT in several cells and tissues exposed to AAPH 19,40–42 . He, Li, Li, Yi, Wang, Tsoi, Lee, Abe, Yang, and Kurihara 19 demonstrated that a brief exposure of AAPH increased lipid peroxidation in the heart of chick embryos.…”

Kinetic Potentiometry as a Method for Studying the Interactions of Antioxidants with Peroxyl Radicals

“…The AAPH (2,2′-azobis-(2-amidinopropane) hydrochloride) is the most common radical generating system. Peroxyl radicals are formed during the thermal decomposition of AAPH [ 7 , 8 , 9 , 10 , 11 ]. The use of radical generating models is quite common in the study of compounds with antioxidant/inhibitory properties.…”

“…This is due to the fact that, firstly, the generated peroxyl radicals model secondary peroxyl radicals formed in the body during the biomolecule oxidation. Secondly, the generation of radicals occurs in time at a certain rate, which is also similar to the radicals of the body, in contrast to model systems with stable radicals [ 7 , 8 ]. The fluorescent, the chemiluminescent, and the spectrophotometric methods are used to assess the inhibitory effect of antioxidants in radical generating systems [ 9 , 10 , 11 , 12 , 13 , 14 ].…”

“…The reaction between generated peroxyl radicals and inhibitors/antioxidants is based on the mechanism of hydrogen atom transfer (HAT-based assays) [ 8 , 9 , 10 ], which in aqueous media can be considered as proton transfer accompanied by electron transfer. In this regard, it is promising to use simple reliable electrochemical methods to study such systems, although their use for radical generating systems is practically not described in the literature.…”

Uncoupling effect of lipid peroxidation in spinach thylakoids exposed to peroxyl radicals generated by 2,2′-azobis (2-amidinopropane) dihydrochloride

“…This water-soluble azo compound is widely used as a model reagent to mimic oxidative stress due to its ability to generate peroxyl radicals at a constant rate at physiological temperatures (Niki 1990). It is used to induce oxidative stress in various in vivo and in vitro biological systems, such as rat lungs (Gomes et al 2016), zebrafishes (Wang et al 2018), chicken embryos (He et al 2013), human erythrocytes (Zou et al 2001) and to induce peroxidation of low-density lipoproteins (Yoshida et al 2004) and of phosphatidylcholine liposomes (Mendez-Sanchez et al 2009). It is also used in ORAC (oxygen radical absorbance capacity) assays to evaluate the antioxidant capacity of different compounds to protect target molecules (e.g., phycoerythrine, fluorescine, pyrogallol red) against peroxyl radicals (Prior et al 2005).…”