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松果体切除术和褪黑素给药对α-萘硫脲诱导的肺水肿的影响。

Pinealectomy and melatonin administration in rats: their effects on pulmonary edema induced by α-naphthylthiourea.

机构信息

Department of Medical Biochemistry, Karabuk University, Karabuk, Turkey.

Department of Histology and Embryology, Mugla Sıtkı Kocman University, Mugla, Turkey.

出版信息

Drug Chem Toxicol. 2023 Nov;46(5):1024-1034. doi: 10.1080/01480545.2022.2119994. Epub 2022 Sep 7.

Abstract

We aimed to observe the possible effects of melatonin (MLT) deprivation (pinealectomy) and exogenous MLT administration on pulmonary edema induced by alpha-naphthylthiourea (ANTU), a toxic chemical agent, in rats. Seventy animals were assigned to seven groups: control, sham pinealectomy (PINX), PINX, ANTU (10 mg/kg intraperitoneal on day 30), ANTU + MLT (10 mg/kg/day i.p. for 30 days), ANTU + PINX, and ANTU + PINX + MLT.In this study, pleural effusion (PE) formation, lung weight/body weight (LW/BW) and PE/BW ratios (fluid accumulation and weight values in the lungs) increase detected. Pre-ANTU MLT administration led to significant decreases in PE, LW/BW, and PE/BW levels. The inhibited glutathione (GSH) and superoxide dismutase (SOD) levels and high malondialdehyde (MDA) levels that ANTU increase lipid peroxidation in the study. MLT administration eliminated oxidative stress by reducing MDA and ameliorating GSH and SOD levels.Pre-ANTU MLT administration led to a significant decrease in interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels in the lung when compared to the ANTU group without MLT administration. Post-pinealectomy ANTU administration significantly increased IL-1β and TNF-α levels when compared to ANTU and MLT administration without pinealectomy. Diffused inflammatory cell infiltration, interstitial pulmonary edema, and histopathological congestion were observed after the administration of ANTU. Severity of the damage was elevated in the ANTU + PINX group. MLT treatment regressed pulmonary effusion and edema and improves lung structure. In brief, the findings suggested that MLT inhibited proinflammatory mediators and could serve as a therapeutic agent to prevent inflammatory disorders.

摘要

我们旨在观察褪黑素(MLT)剥夺(松果体切除术)和外源性 MLT 给药对α-萘基硫脲(ANTU)诱导的肺水肿的可能影响,ANTU 是一种有毒化学物质。70 只动物被分配到七个组:对照组、假松果体切除术(PINX)、PINX、ANTU(30 天第 10 天腹腔内 10mg/kg)、ANTU+MLT(30 天每天腹腔内 10mg/kg)、ANTU+PINX 和 ANTU+PINX+MLT。在这项研究中,发现胸腔积液(PE)形成、肺重/体重(LW/BW)和 PE/BW 比值(肺部积液和重量值)增加。预先给予 ANTU MLT 可显著降低 PE、LW/BW 和 PE/BW 水平。ANTU 增加的抑制谷胱甘肽(GSH)和超氧化物歧化酶(SOD)水平和高丙二醛(MDA)水平表明脂质过氧化作用增强。MLT 通过降低 MDA 并改善 GSH 和 SOD 水平来消除氧化应激。与未给予 MLT 的 ANTU 组相比,预先给予 ANTU MLT 可显著降低肺中白细胞介素 1β(IL-1β)和肿瘤坏死因子-α(TNF-α)水平。与未行松果体切除术的 ANTU 和 MLT 组相比,术后给予 ANTU 后松果体切除术组 IL-1β 和 TNF-α 水平显著升高。给予 ANTU 后观察到弥漫性炎症细胞浸润、间质肺水肿和组织病理学充血。ANTU+PINX 组损伤程度升高。MLT 治疗可消退肺渗出和水肿,并改善肺结构。简而言之,这些发现表明 MLT 抑制促炎介质,可作为预防炎症性疾病的治疗剂。

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