关键词: apoptosis carvacrol inflammation lung toxicity mercuric chloride oxidative stress

来  源:   DOI:10.1002/tox.24397

Abstract:
Mercuric chloride (HgCl2) is extremely toxic to both humans and animals. It could be absorbed via ingestion, inhalation, and skin contact. Exposure to HgCl2 can cause severe health effects, including damages to the gastrointestinal, respiratory, and central nervous systems. The purpose of this work was to explore if carvacrol (CRV) could protect rats lungs from damage caused by HgCl2. Intraperitoneal injections of HgCl2 at a dose of 1.23 mg/kg body weight were given either alone or in conjunction with oral CRV administration at doses of 25 and 50 mg/kg body weight for 7 days. The study included biochemical and histological techniques to examine the lung tissue\'s oxidative stress, apoptosis, inflammation, and autophagy processes. HgCl2-induced reductions in GSH levels and antioxidant enzymes (SOD, CAT, and GPx) activity were enhanced by CRV co-administration. Furthermore, MDA levels were lowered by CRV. The inflammatory mediators NF-κB, IκB, NLRP3, TNF-α, IL-1β, IL6, COX-2, and iNOS were all reduced by CRV. When exposed to HgCl2, the levels of apoptotic Bax, caspase-3, Apaf1, p53, caspase-6, and caspase-9 increased, but the levels of antiapoptotic Bcl-2 reduced after CRV treatment. CRV decreased levels of Beclin-1, LC3A, and LC3B, which in turn decreased HgCl2-induced autophagy damage. After HgCl2 treatment, higher pathological damage was observed in terms of alveolar septal thickening, congestion, edema, and inflammatory cell infiltration compared to the control group while CRV ameliorated these effects. Consequently, by preventing HgCl2-induced increases in oxidative stress and the corresponding inflammation, autophagy, apoptosis, and disturbance of tissue integrity in lung tissues, CRV might be seen as a useful therapeutic alternative.
摘要:
氯化汞(HgCl2)对人类和动物都有剧毒。它可以通过摄入吸收,吸入,皮肤接触。接触HgCl2会对健康造成严重影响,包括对胃肠道的损害,呼吸,和中枢神经系统。这项工作的目的是探索香芹酚(CRV)是否可以保护大鼠肺免受HgCl2引起的损伤。以1.23mg/kg体重的剂量腹膜内注射HgCl2单独给予或与以25和50mg/kg体重的剂量口服CRV一起给予7天。这项研究包括生化和组织学技术,以检查肺组织的氧化应激,凋亡,炎症,和自噬过程。HgCl2诱导的GSH水平和抗氧化酶的降低(SOD,CAT,和GPx)活性通过CRV共同施用而增强。此外,CRV降低了MDA水平。炎症介质NF-κB,IκB,NLRP3,TNF-α,IL-1β,IL6、COX-2和iNOS均被CRV降低。当暴露于HgCl2时,凋亡Bax的水平,caspase-3,Apaf1,p53,caspase-6和caspase-9增加,但CRV治疗后抗凋亡Bcl-2水平降低。CRV降低了Beclin-1,LC3A,LC3B,这反过来减少了HgCl2诱导的自噬损伤。HgCl2处理后,在肺泡间隔增厚方面观察到更高的病理损害,拥塞,水肿,与对照组相比,CRV改善了这些作用。因此,通过防止HgCl2诱导的氧化应激和相应的炎症增加,自噬,凋亡,和肺组织中组织完整性的干扰,CRV可能被视为一种有用的治疗替代方案。
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