The protective effects of apocynin in hyperoxic lung injury in neonatal rats

Abstract

Aim: Inflammation and oxidate stress are significant factors in the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of this study is to investigate the efficacy of apocynin (APO), an anti-inflammatory, antioxidant, and antiapoptotic drug, in the prophylaxis of neonatal hyperoxic lung injury.Method: This experimental study included 40 neonatal rats divided into the control, APO, BPD, and BPD + APO groups. The control and APO groups were kept in a normal room environment, while the BPD and BPD + APO groups were kept in a hyperoxic environment. The rats in the APO and BPD + APO groups were administered intraperitoneal APO, while the control and BPD rats were administered ordinary saline. At the end of the trial, lung tissue was evaluated with respect to the degree of histopathological injury, apoptosis, oxidant and antioxidant capacity, and severity of inflammation. Result:The BPD and BPD + APO groups exhibited higher mean histopathological injury and alveolar macrophage scores compared to the control and APO groups.Both scores were lower in the BPD + APO group in comparison to the BPD group.The BPD + APO group had a significantly lower average of TUNEL positive cells than the BPD group. The lung tissue examination indicated significantly higher levels of mean malondialdehyde (MDA), total oxidant status (TOS), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in the BPD group compared to the control and APO groups. While the TNF-α and IL-1β levels of the BPD + APO group were similar to that of the control group, the MDA and TOS levels were higher compared to the controls and lower compared to the BPD group. The BPD group demonstrated significantly lower levels/activities of mean total antioxidant status, glutathione reductase, superoxide dismutase, glutathione peroxidase in comparison to the control and APO groups. While the mean antioxidant enzyme activity of the BPD + APO group was lower than the control group, it was significantly higher compared to the BPD group. Conclusion:This is the first study in the literature to reveal through an experimental neonatal hyperoxic lung injury that APO, an anti-inflammatory, antioxidant, and antiapoptotic drug, exhibits protective properties against the development of BPD.

The Effects of Apocynin on Selenite-induced Cataract Established in Rats

“…There have been shown to be different effects of apocynin used in animal models on antioxidant enzymes. measured in different tissues [37,38]. Low-dose (10 mg/kg) and high-dose (20 mg/kg) apocynin have been reported to show similar antioxidant activity in acute lung injury [38] and hyperoxic lung injury [37], but there are no previous studies in which both doses have been studied in the cataract simultaneously.…”

“…measured in different tissues [37,38]. Low-dose (10 mg/kg) and high-dose (20 mg/kg) apocynin have been reported to show similar antioxidant activity in acute lung injury [38] and hyperoxic lung injury [37], but there are no previous studies in which both doses have been studied in the cataract simultaneously. The current study included both doses of apocynin in a selenite-induced cataract model in rats and thus comparisons were made between doses.…”

Cryptotanshinone affects HFL-1 cells proliferation by inhibiting cytokines secretion in RAW264.7 cells and ameliorates inflammation and fibrosis in newborn rats with hyperoxia induced lung injury

“…Based on previous reports ( Xu et al, 2019 ; Pang et al, 2021 ), for fibrosis scoring, the degree of fibrosis was graded into three categories: grade 0: no substantial fibrosis throughout the lung; grade 1: mild fibrosis (20%); grade 2: moderate fibrosis (20%–50%); and grade 3: severe fibrosis (>50%). Furthermore, the number of mononuclear cells was also calculated for each group ( Ozdemir et al, 2022 ), and 10 fields of view were randomly selected for counting in each section.…”

“…Moreover, alveolar macrophages can be activated in response to hyperoxia, leading to abnormal lung development in immature mice ( Kalymbetova et al, 2018 ). Macrophages not only secrete pro-inflammatory cytokines such as interleukin (IL)-6, tumour necrosis factor (TNF)-α and the pro-fibrotic growth factor transforming growth factor (TGF)-β1 ( Holzfurtner et al, 2022 ; Ozdemir et al, 2022 ), which regulate the intracellular immune response, but also play an essential role in the late repair phase of lung injury. These macrophage-secreted cytokines trigger fibroblasts to differentiate into activated myofibroblasts, thus promoting fibroblast recruitment and proliferation and leading to excessive collagen fiber accumulation, which eventually leads to pulmonary fibrosis ( Sayan and Mossman, 2016 ; Barnes et al, 2019 ).…”