Mamdouh Eldesoqui , Eman M. Embaby , Rania A. Fouad , Yara M. Alrajhi , Zeinab A. Mohammed , Emad A. Albadawi , Rasha Hamed Al‑Serwi , Ahmed A. El-Mansi , Mahmoud Hendawy , Magda E. Ahmed
{"title":"姜黄素通过Nrf2/HO-1、NF-κB/TNF-α和COX-2通路调节氧化应激、炎症和纤维化,减轻马拉硫磷诱导的大鼠肺损伤。","authors":"Mamdouh Eldesoqui , Eman M. Embaby , Rania A. Fouad , Yara M. Alrajhi , Zeinab A. Mohammed , Emad A. Albadawi , Rasha Hamed Al‑Serwi , Ahmed A. El-Mansi , Mahmoud Hendawy , Magda E. Ahmed","doi":"10.1016/j.tice.2025.103144","DOIUrl":null,"url":null,"abstract":"<div><h3>Background<em>:</em></h3><div>Malathion (Mal), a commonly used organophosphate insecticide, causes significant lung damage through oxidative stress, inflammation, and stimulation of pulmonary fibrosis. Curcumin (Cur), a natural polyphenolic molecule, possesses strong antioxidant, anti-inflammatory, and antifibrotic functions.</div></div><div><h3>Objective</h3><div>This work aimed to evaluate the protective effects of Cur against Mal-induced lung injury in rats by modulating the Nrf2/HO-1, NF-κB/TNF-α, and COX-2 signaling pathways.</div></div><div><h3>Methods</h3><div>Twenty-four adult male Sprague Dawley rats were randomly divided into four equal groups: control, Cur-treated (150 mg/kg/day), Mal-treated (100 mg/kg/day), and Mal+Cur (received Cur followed by Mal after 3 h) groups. Both Mal and Cur were administered orally via gavage for four weeks. Oxidative stress markers, inflammatory mediators, and fibrotic alterations were assessed in lung tissues using biochemical and histological methods. The expression of key signaling molecules, including Nrf2/HO-1 (antioxidant response), NF-κB/TNF-α (inflammatory response), and COX-2 (pro-inflammatory enzyme), was measured via immunohistochemistry and quantitative PCR.</div></div><div><h3>Results</h3><div>Compared to the control group<em>,</em> Mal exposure led to marked oxidative damage, evidenced by elevated Malondialdehyde (MDA) levels (p < 0.0001) and decreased superoxide dismutase (SOD) and acetylcholinesterase (AChE) levels (p < 0.0001). This was accompanied by increased expression of pro-inflammatory (TNF-α, IL-1β, IL-6, and PGE2 (p < 0.0001)) and pro-fibrotic (hydroxyproline) markers, and significant histopathological alterations. Co-administration of curcumin significantly attenuated these effects, restoring AChE activity, enhancing Nrf2/HO-1/ antioxidant signaling, and suppressing NF-κB/TNF-α and COX-2 inflammatory pathways.</div></div><div><h3>Conclusion<em>:</em></h3><div>These data demonstrate that curcumin protects against malathion-induced lung injury by modulating oxidative stress, inflammation, and fibrosis-related pathways, highlighting its therapeutic potential for mitigating organophosphate-induced respiratory damage.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103144"},"PeriodicalIF":2.5000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Curcumin attenuates malathion-induced lung injury in rats by modulating oxidative stress, inflammation, and fibrosis via Nrf2/HO-1, NF-κB/TNF-α, and COX-2 pathways.\",\"authors\":\"Mamdouh Eldesoqui , Eman M. Embaby , Rania A. Fouad , Yara M. Alrajhi , Zeinab A. Mohammed , Emad A. Albadawi , Rasha Hamed Al‑Serwi , Ahmed A. El-Mansi , Mahmoud Hendawy , Magda E. Ahmed\",\"doi\":\"10.1016/j.tice.2025.103144\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background<em>:</em></h3><div>Malathion (Mal), a commonly used organophosphate insecticide, causes significant lung damage through oxidative stress, inflammation, and stimulation of pulmonary fibrosis. Curcumin (Cur), a natural polyphenolic molecule, possesses strong antioxidant, anti-inflammatory, and antifibrotic functions.</div></div><div><h3>Objective</h3><div>This work aimed to evaluate the protective effects of Cur against Mal-induced lung injury in rats by modulating the Nrf2/HO-1, NF-κB/TNF-α, and COX-2 signaling pathways.</div></div><div><h3>Methods</h3><div>Twenty-four adult male Sprague Dawley rats were randomly divided into four equal groups: control, Cur-treated (150 mg/kg/day), Mal-treated (100 mg/kg/day), and Mal+Cur (received Cur followed by Mal after 3 h) groups. Both Mal and Cur were administered orally via gavage for four weeks. Oxidative stress markers, inflammatory mediators, and fibrotic alterations were assessed in lung tissues using biochemical and histological methods. The expression of key signaling molecules, including Nrf2/HO-1 (antioxidant response), NF-κB/TNF-α (inflammatory response), and COX-2 (pro-inflammatory enzyme), was measured via immunohistochemistry and quantitative PCR.</div></div><div><h3>Results</h3><div>Compared to the control group<em>,</em> Mal exposure led to marked oxidative damage, evidenced by elevated Malondialdehyde (MDA) levels (p < 0.0001) and decreased superoxide dismutase (SOD) and acetylcholinesterase (AChE) levels (p < 0.0001). This was accompanied by increased expression of pro-inflammatory (TNF-α, IL-1β, IL-6, and PGE2 (p < 0.0001)) and pro-fibrotic (hydroxyproline) markers, and significant histopathological alterations. Co-administration of curcumin significantly attenuated these effects, restoring AChE activity, enhancing Nrf2/HO-1/ antioxidant signaling, and suppressing NF-κB/TNF-α and COX-2 inflammatory pathways.</div></div><div><h3>Conclusion<em>:</em></h3><div>These data demonstrate that curcumin protects against malathion-induced lung injury by modulating oxidative stress, inflammation, and fibrosis-related pathways, highlighting its therapeutic potential for mitigating organophosphate-induced respiratory damage.</div></div>\",\"PeriodicalId\":23201,\"journal\":{\"name\":\"Tissue & cell\",\"volume\":\"98 \",\"pages\":\"Article 103144\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tissue & cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0040816625004264\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ANATOMY & MORPHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue & cell","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0040816625004264","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}
Curcumin attenuates malathion-induced lung injury in rats by modulating oxidative stress, inflammation, and fibrosis via Nrf2/HO-1, NF-κB/TNF-α, and COX-2 pathways.
Background:
Malathion (Mal), a commonly used organophosphate insecticide, causes significant lung damage through oxidative stress, inflammation, and stimulation of pulmonary fibrosis. Curcumin (Cur), a natural polyphenolic molecule, possesses strong antioxidant, anti-inflammatory, and antifibrotic functions.
Objective
This work aimed to evaluate the protective effects of Cur against Mal-induced lung injury in rats by modulating the Nrf2/HO-1, NF-κB/TNF-α, and COX-2 signaling pathways.
Methods
Twenty-four adult male Sprague Dawley rats were randomly divided into four equal groups: control, Cur-treated (150 mg/kg/day), Mal-treated (100 mg/kg/day), and Mal+Cur (received Cur followed by Mal after 3 h) groups. Both Mal and Cur were administered orally via gavage for four weeks. Oxidative stress markers, inflammatory mediators, and fibrotic alterations were assessed in lung tissues using biochemical and histological methods. The expression of key signaling molecules, including Nrf2/HO-1 (antioxidant response), NF-κB/TNF-α (inflammatory response), and COX-2 (pro-inflammatory enzyme), was measured via immunohistochemistry and quantitative PCR.
Results
Compared to the control group, Mal exposure led to marked oxidative damage, evidenced by elevated Malondialdehyde (MDA) levels (p < 0.0001) and decreased superoxide dismutase (SOD) and acetylcholinesterase (AChE) levels (p < 0.0001). This was accompanied by increased expression of pro-inflammatory (TNF-α, IL-1β, IL-6, and PGE2 (p < 0.0001)) and pro-fibrotic (hydroxyproline) markers, and significant histopathological alterations. Co-administration of curcumin significantly attenuated these effects, restoring AChE activity, enhancing Nrf2/HO-1/ antioxidant signaling, and suppressing NF-κB/TNF-α and COX-2 inflammatory pathways.
Conclusion:
These data demonstrate that curcumin protects against malathion-induced lung injury by modulating oxidative stress, inflammation, and fibrosis-related pathways, highlighting its therapeutic potential for mitigating organophosphate-induced respiratory damage.
期刊介绍:
Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed.
Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.