Toxicology Reports最新文献_第10页

L-arginine supplement ameliorates dichlorvos-induced systemic inflammatory response and liver dysfunction in male wistar rats

Q1 Environmental Science

Toxicology Reports

Pub Date : 2024-12-12 DOI: 10.1016/j.toxrep.2024.101846

W.A. Saka , Y.D. Igbayilola , H.J. Lawan , M.B. Zakari , D.E. Awujoola , P.O. Olarinde , V.O. Adegoke

Dichlorvos (DDVP), a frequently used organophosphate insecticide, has been shown to cause systemic inflammation and liver damage via oxidative stress and inflammatory pathways. L-arginine, a semi-essential amino acid, has been shown to protect against oxidative damage and inflammation in a variety of animals. The study's main goal was to raise awareness of Dichlorvos's (DDVP) harmful effects on systemic inflammation and liver function, as well as L-arginine's possible mitigating impact. In order to assess the preventive benefits of L-arginine against induced liver dysfunction and systemic inflammation, liver tissue was selected for this investigation due to its vital role in detoxification and its high susceptibility to harm from toxic chemicals such as Dichlorvos. A total of 40 adult Wistar rats were separated into four groups: control, dichlorvos only, L-arginine only, and dichlorvos plus L-arginine. Dichlorvos was provided orally at a dose of 8 mg/kg body weight, whereas L-arginine was given orally at a dose of 100 mg/kg body weight for six weeks. The study investigated systemic inflammation markers (C-reactive protein, TNF-α, IL-6, and Caspase 3) as well as liver function markers (ALT, AST, ALP, albumin, total protein and gamma glutamyl). The findings revealed that dichlorvos significantly (p < 0.05) enhanced systemic inflammation and decreased (p < 0.05) liver function when compared to the control group. However, L-arginine supplementation greatly improved these effects by significantly (p < 0.05) lowering inflammatory indicators and restoring liver enzyme levels to normal. Histopathological findings validated L-arginine's protective function against dichlorvos-induced liver injury. These data indicate that L-arginine supplement may reduce the negative effects of dichlorvos on systemic inflammation and liver function, providing a possible therapeutic method for controlling organophosphate toxicity.

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引用次数: 0

Gossypol enhances ponatinib's cytotoxicity against human hepatocellular carcinoma cells by involving cell cycle arrest, p-AKT/LC3II/p62, and Bcl2/caspase-3 pathways 棉酚通过参与细胞周期阻滞、p-AKT/LC3II/p62和Bcl2/caspase-3途径增强ponatinib对人肝癌细胞的细胞毒性。

Q1 Environmental Science

Toxicology Reports

Pub Date : 2024-12-11 DOI: 10.1016/j.toxrep.2024.101856

Hadeel H. Elkattan , Alaa E. Elsisi , Naglaa M. El-Lakkany

Despite significant breakthroughs in frontline cancer research and chemotherapy for hepatocellular carcinoma (HCC), many of the suggested drugs have high toxic side effects and resistance, limiting their clinical utility. Exploring potential therapeutic targets or novel combinations with fewer side effects is therefore crucial in combating this dreadful disease. The current study aims to use a novel combination of ponatinib and gossypol against the HepG2 cell line. Cell survival, FGF19/FGFR4, apoptotic and autophagic cell death, and synergistic drug interactions were assessed in response to increasing concentrations of ponatinib and/or gossypol treatment. Research revealed that ponatinib (1.25–40 μM) and gossypol (2.5–80 μM) reduced the viability of HepG2 cells in a way that was dependent on both time and dose. Ponatinib's anti-proliferation effectiveness was improved synergistically by gossypol and was associated with a rise in apoptotic cell death, cell cycle blockage during the G0/G1 phase, and suppression of the FGF19/FGFR4 axis. Furthermore, the ponatinib/gossypol combination lowered Bcl-2 and p-Akt while increasing active caspase-3, Beclin-1, p62, and LC3II. This combination, however, had no harm on normal hepatocytes. Overall, gossypol enhanced ponatinib's anticancer effects in HCC cells. Notably, this new combination appears to be potential adjuvant targeted chemotherapy, a discovery that warrants more clinical investigation, in the management of patients with HCC.

尽管一线癌症研究和肝细胞癌（HCC）化疗取得了重大突破，但许多推荐的药物具有高毒副作用和耐药性，限制了它们的临床应用。因此，探索潜在的治疗靶点或副作用较小的新组合对于对抗这种可怕的疾病至关重要。目前的研究旨在使用波纳替尼和棉酚的新组合来对抗HepG2细胞系。细胞存活、FGF19/FGFR4、凋亡和自噬细胞死亡以及协同药物相互作用在增加ponatinib和/或棉酚治疗浓度时进行了评估。研究发现，ponatinib （1.25 ~ 40 μM）和棉酚（2.5 ~ 80 μM）对HepG2细胞的活性有一定的降低作用，且降低作用的方式与时间和剂量有关。Ponatinib的抗增殖效果与棉酚协同提高，并与凋亡细胞死亡增加、G0/G1期细胞周期阻滞和FGF19/FGFR4轴抑制有关。此外，波纳替尼/棉酚组合降低Bcl-2和p-Akt，同时增加活性caspase-3、Beclin-1、p62和LC3II。然而，这种组合对正常肝细胞没有损害。总之，棉酚增强了波纳替尼在HCC细胞中的抗癌作用。值得注意的是，这种新的组合似乎是潜在的辅助靶向化疗，这一发现值得更多的临床研究，用于HCC患者的管理。

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引用次数: 0

Fenofibrate ameliorated atorvastatin and piperine-induced ROS mediated reproductive toxicity in male Wistar rats 非诺贝特改善了阿托伐他汀和胡椒碱诱导的雄性Wistar大鼠ROS介导的生殖毒性。

Q1 Environmental Science

Toxicology Reports

Pub Date : 2024-12-10 DOI: 10.1016/j.toxrep.2024.101861

Sanjib Ghosh , Sweata Sarkar , Maharaj Biswas

Atorvastatin and fenofibrate are well-known lipid-lowering drugs. Atorvastatin acts by reducing the production of cholesterol through the inhibition of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG Co-A reductase) enzyme, whereas fenofibrate is a PPAR-α agonist. Piperine is an alkaloid mostly found in black pepper fruits. The present study was planned to evaluate the activities of atorvastatin, fenofibrate, and piperine on the male reproductive system. A total of 35 male Wistar rats were obtained for the experiment. Rats were randomly divided into 7 groups, each group with 5 rats. The experiment was run for 28 days. Group I rat got normal meals for 28 days; Group II received atorvastatin (08 mg/kg/day); Group III received piperine (10 mg/kg/day); and Group IV received fenofibrate (20 mg/kg/day). Group V received atorvastatin (8 mg/kg/day) and piperine (10 mg/kg/day); Group VI received piperine (10 mg/kg/day) and fenofibrate (20 mg/kg/day). VII received fenofibrate (20 mg/kg bw/day) and atorvastatin (8 mg/kg/day). After sacrifice, serum and testicular cholesterol and testosterone levels assessed by ELISA, ROS generation analysed by using flow cytometry, MDA, SOD, and catalase were measured. Histological, sperm-parameter analysis, and spermatogenic evaluations were also done. Activities of atorvastatin and piperine revealed reproductive toxicity upon treatment. Fenofibrate treatment, along with atorvastatin and piperine, showed protective effects. In conclusion, atorvastatin and piperine affected reproductive potential, whereas fenofibrate might have protective efficacy against atorvastatin and piperine-induced reproductive toxicity.

阿托伐他汀和非诺贝特是众所周知的降脂药物。阿托伐他汀通过抑制3-羟基-3-甲基-戊二酰辅酶A还原酶（HMG Co-A还原酶）来减少胆固醇的产生，而非诺贝特是一种PPAR-α激动剂。胡椒碱是一种主要存在于黑胡椒果实中的生物碱。本研究旨在评价阿托伐他汀、非诺贝特和胡椒碱对男性生殖系统的作用。实验选用雄性Wistar大鼠35只。将大鼠随机分为7组，每组5只。试验期28 d。ⅰ组大鼠正常饲喂28 d；II组给予阿托伐他汀（08 mg/kg/天）；III组给予胡椒碱（10 mg/kg/天）；IV组给予非诺贝特（20 mg/kg/天）。V组给予阿托伐他汀（8 mg/kg/天）和胡椒碱（10 mg/kg/天）；VI组给予胡椒碱（10 mg/kg/天）和非诺贝特（20 mg/kg/天）。患者接受非诺贝特（20 mg/kg体重/天）和阿托伐他汀（8 mg/kg/天）治疗。牺牲后，ELISA检测血清和睾丸胆固醇、睾酮水平，流式细胞术检测ROS生成，测定MDA、SOD和过氧化氢酶水平。同时进行组织学、精子参数分析和生精性评价。治疗后，阿托伐他汀和胡椒碱的活性显示出生殖毒性。非诺贝特治疗，以及阿托伐他汀和胡椒碱，显示出保护作用。综上所述，阿托伐他汀和胡椒碱影响生殖潜能，而非诺贝特可能对阿托伐他汀和胡椒碱诱导的生殖毒性具有保护作用。

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引用次数: 0

Effects of dietary acrylamide on kidney and liver health: Molecular mechanisms and pharmacological implications 膳食丙烯酰胺对肾脏和肝脏健康的影响：分子机制和药理意义。

Q1 Environmental Science

Toxicology Reports

Pub Date : 2024-12-10 DOI: 10.1016/j.toxrep.2024.101859

Mohammed Nazish Quasmi, Dinesh Kumar, Ashok Jangra

Acrylamide (AA) has raised concerns throughout the world in recent years because of its potential negative effects on human health. Numerous researches on humans and animals have connected a high dietary exposure to AA to a possible risk of cancer. Additionally, higher consumption of acrylamide has also been associated with dysfunctioning of various organ systems from nervous system to the reproductive system. Acrylamide is primarily metabolised into the glycidamide inside the body which gets accumulated in different tissues including kidney and liver, and chronic exposure to this can lead to the nephrotoxicity and hepatotoxicity through different molecular mechanisms. This review summarizes the various sources, formation and metabolism of the dietary acrylamide along with the different molecular mechanisms such as oxidative stress, inflammation, DNA damage, autophagy, mitochondrial dysfunction and morphological changes in nephron and hepatocytes through which acrylamide exerts its deleterious effect on kidney and liver causing nephrotoxicity and hepatotoxicity. This review summarizes various animal and cellular studies that demonstrate AA-induced nephrotoxicity and hepatotoxicity. Lastly, the article emphasizes on underlying protective molecular mechanisms of various pharmacological interventions against acrylamide induced hepatotoxicity and nephrotoxicity

近年来，丙烯酰胺（AA）因其对人体健康的潜在负面影响而引起了全世界的关注。对人类和动物的大量研究表明，饮食中大量摄入AA与癌症的可能风险有关。此外，过量摄入丙烯酰胺还与从神经系统到生殖系统的各种器官系统功能失调有关。丙烯酰胺主要在体内代谢成缩水甘油酰胺，在不同的组织中积累，包括肾脏和肝脏，长期接触丙烯酰胺可通过不同的分子机制导致肾毒性和肝毒性。本文综述了膳食丙烯酰胺的来源、形成和代谢，以及丙烯酰胺通过氧化应激、炎症、DNA损伤、自噬、线粒体功能障碍和肾细胞和肝细胞形态学改变等不同的分子机制对肾脏和肝脏产生有害作用，引起肾毒性和肝毒性。本文综述了各种动物和细胞研究，证明了aa引起的肾毒性和肝毒性。最后，文章强调了各种药物干预对丙烯酰胺引起的肝毒性和肾毒性的潜在保护分子机制。

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引用次数: 0

Interleukin-10 levels in azithromycin-induced cardiac damage and the protective role of combined selenium and vitamin E treatment 阿奇霉素所致心脏损伤中的白细胞介素-10水平及硒和维生素E联合治疗的保护作用。

Q1 Environmental Science

Toxicology Reports

Pub Date : 2024-12-10 DOI: 10.1016/j.toxrep.2024.101860

Heba Hussein Rohym , Mohamed S. Hemeda , Almoatazbellah Mahmoud Elsayed , Mayada Saad Farrag , Heba A. Elsayed , Amgad A. Ezzat , Mohamed A. Ibrahim , Mohammed Makloph

Azithromycin is a broad-spectrum antibiotic commonly used to treat bacterial infections but is associated with adverse cardiac effects, including oxidative damage and myocardial inflammation. This study aims to explore the histopathological and biochemical changes, including serum interleukin-10 levels, induced by azithromycin in the hearts of male albino rats and to evaluate the protective role of combined selenium and vitamin E treatment. Forty rats were divided into four groups: a control group, an azithromycin treatment group, selenium and vitamin E treatment group, and a combined treatment group receiving both azithromycin, selenium, and vitamin E. Results showed that the azithromycin-treated group exhibited significant increases in interleukin-10 levels, myocardial fibrosis, and cell structure degeneration, while combined selenium and vitamin E treatment markedly reduced these adverse effects, indicating a protective effect. This study concludes that selenium and vitamin E provide a protective effect against azithromycin-induced cardiac toxicity, suggesting that concurrent antioxidant therapy may help safeguard the heart during azithromycin treatment.

阿奇霉素是一种广谱抗生素，常用于治疗细菌感染，但对心脏有不良影响，包括氧化损伤和心肌炎。本研究旨在探讨阿奇霉素在雄性白化大鼠心脏中诱导的组织病理学和生化变化，包括血清白细胞介素-10水平，并评估硒和维生素E联合治疗的保护作用。结果表明，阿奇霉素治疗组的白细胞介素-10水平、心肌纤维化和细胞结构变性显著增加，而硒和维生素 E的联合治疗则明显减轻了这些不良反应，显示出保护作用。本研究的结论是，硒和维生素 E 对阿奇霉素诱发的心脏毒性具有保护作用，这表明在阿奇霉素治疗期间，同时进行抗氧化治疗可能有助于保护心脏。

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引用次数: 0

Cytotoxicity evaluation of microbial sophorolipids and glucolipids using normal human dermal fibroblasts (NHDF) in vitro 体外使用正常人真皮成纤维细胞（NHDF）评价微生物皂荚脂和糖脂的细胞毒性。

Q1 Environmental Science

Toxicology Reports

Pub Date : 2024-12-10 DOI: 10.1016/j.toxrep.2024.101862

Sergio Oliveira Formoso , Vincent Chaleix , Niki Baccile , Christophe Helary

Fibroblasts are considered a key player in the wound healing process. Although this cellular family is constituted by several distinct subtypes, dermal fibroblasts are crucial thanks to their ability to secrete pro-regenerative growth factors, extracellular matrix (ECM) proteins and their immune and anti-inflammatory role. Sophorolipids (SL), sophorosides (SS) and glucolipids (G), mono-unsaturated (C18:1) or saturated (C18:0), glycolipids derived from microbial fermentation of wild type or engineered yeast Starmerella bombicola, constitute a novel sustainable class of bio-based chemicals with interesting physicochemical characteristics, which allow them to form soft diverse structures from hydrogels to vesicles, micelles or complex coacervates with potential interest in skin regeneration applications. In this study, we first tested the cytocompatibility of a broad set of molecules from this family on normal human dermal fibroblasts (NHDF). Our results show that, up to an upper threshold (0.1 % w/v), the microbial glycolipids (SL-C18:1, G-C18:1, SS_bola-C18:1, SL-C18:0 and G-C18:0) under study were able to sustain cell growth. Furthermore, we selected the least cytotoxic glycolipids (SL-C18:1, SS_bola-C18:1, SL-C18:0) to study their potential to promote wound healing by measuring the gene expression of several key skin regeneration markers (i.e. collagen, elastin, transforming growth factor β, fibroblast growth factor …) using qPCR. Unfortunately, none of these glycolipids modulated the gene expression of molecules involved in tissue repair. However, this study aims to encourage the community to test this novel class of molecules for novel high-end biomedical applications.

Importance

Biosurfactants prepared by microbial fermentation are natural amphiphiles of growing importance, with the goal of replacing synthetic surfactants in commercial formulations. However, their cytotoxicity profile is still poorly known, especially for new molecules like single-glucose lipids or bolaform sophorolipids. This wants to contribute to all those applications, which could be developed with biosurfactants in contact with the skin (cosmetics, wound healing). We test the cytotoxicity of five structurally-related molecules (C18:1 and C18:0 sophorolipids, C18:1 and C18:0 single-glucose lipids, C18:1 di-sophoroside) against normal human dermal fibroblasts (NHDF) and evaluate the metabolic activity of the least toxic among them. To the best of our knowledge, cytotoxicity of these molecules, and of microbial biosurfactants in general, was never tested against NHDF.

成纤维细胞被认为是伤口愈合过程中的关键角色。尽管真皮成纤维细胞家族由几个不同的亚型组成，但由于它们能够分泌促再生生长因子、细胞外基质（ECM）蛋白以及它们的免疫和抗炎作用，真皮成纤维细胞至关重要。苦槐脂（SL），苦槐苷（SS）和糖脂(G)，单不饱和（C18:1）或饱和（C18:0），糖脂来源于野生型或工程酵母的微生物发酵，构成了一类新的可持续的生物基化学物质，具有有趣的物理化学特性，使它们能够形成从水凝胶到囊泡，胶束或复杂凝聚的柔软多样结构，具有潜在的皮肤再生应用兴趣。在这项研究中，我们首先测试了来自该家族的一系列分子在正常人类真皮成纤维细胞（NHDF）上的细胞相容性。我们的研究结果表明，在所研究的微生物糖脂（SL-C18:1, G-C18:1, sbola - c18:1， SL-C18:0和G-C18:0）能够维持细胞生长的上限（0.1 % w/v）。此外，我们选择了细胞毒性最小的糖脂（SL-C18:1, SSbola-C18:1, SL-C18:0），通过使用qPCR测量几种关键皮肤再生标志物（如胶原蛋白，弹性蛋白，转化生长因子β，成纤维细胞生长因子等）的基因表达来研究它们促进伤口愈合的潜力。不幸的是，这些糖脂都不能调节参与组织修复的分子的基因表达。然而，这项研究旨在鼓励社区测试这类新型分子用于新型高端生物医学应用。重要性：微生物发酵制备的生物表面活性剂是日益重要的天然两亲性物质，其目标是取代商业配方中的合成表面活性剂。然而，它们的细胞毒性谱仍然知之甚少，特别是对新分子，如单葡萄糖脂质或博拉form苦参脂质。这将有助于所有与皮肤接触的生物表面活性剂（化妆品，伤口愈合）的应用。我们测试了五种结构相关分子（C18:1和C18:0槐脂、C18:1和C18:0单糖脂、C18:1二槐苷）对正常人真皮成纤维细胞（NHDF）的细胞毒性，并评估了其中毒性最小的代谢活性。据我们所知，这些分子的细胞毒性，以及微生物生物表面活性剂，从未对NHDF进行过测试。

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引用次数: 0

Microplastics bioaccumulation in fish: Its potential toxic effects on hematology, immune response, neurotoxicity, oxidative stress, growth, and reproductive dysfunction 微塑料在鱼类体内的生物积累：其对血液学、免疫反应、神经毒性、氧化应激、生长和生殖功能障碍的潜在毒性影响。

Q1 Environmental Science

Toxicology Reports

Pub Date : 2024-12-09 DOI: 10.1016/j.toxrep.2024.101854

Tapas Ghosh

After being exposed, microplastics mostly bioaccumulated in guts and gills of fish, then, through circulation, spread and bioaccumulated in other tissues. Circulatory system of fish is impacted by the microplastic bioaccumulation in their tissues, influencing a number of hematological indices that are connected with immunity, osmotic pressure, blood clotting, molecular transport and fat metabolism. Variables like size, dose, duration, food consumption and species, all affect the bioaccumulation and toxicity of the microplastic, rather than the exposure routes. Microplastics lead to an imbalance in the generation of ROS and antioxidant defense of fish, which resulting in oxidative injury. Moreover, microplastics affect immunological responses through physico-chemical damage, hence produce neurotoxicity and modifies the activity of the acetylcholine esterase. Exposure to microplastics caused damage to the hepatic and gut tissue, affect intestinal barrier function and dysbiosis of microbial composition, altered the metabolism of host, affecting the activities of the digestive enzymes, eventually affecting the growth performance of fish. Microplastics exposure target the HPG axis and interfere with the process of steroidogenesis, apoptosis of the gonadal tissue, ultimately causing reproductive dysfunction. Fish exposed to microplastics have a range of toxic effects viz. alteration to immune, antioxidant and hematological indices, bioaccumulation, neurotoxicity, growth and reproductive dysfunction, all were examined in this present review by using different indicators.

微塑料暴露后，主要在鱼的内脏和鳃中进行生物积累，然后通过循环扩散并在其他组织中进行生物积累。鱼类的循环系统受到其组织中微塑料生物积累的影响，影响与免疫、渗透压、血液凝固、分子运输和脂肪代谢相关的许多血液学指标。大小、剂量、持续时间、食物消耗和种类等变量都会影响微塑料的生物积累和毒性，而不是接触途径。微塑料导致鱼类体内活性氧生成和抗氧化防御失衡，导致氧化损伤。此外，微塑料通过物理化学损伤影响免疫反应，从而产生神经毒性并改变乙酰胆碱酯酶的活性。微塑料暴露导致肝脏和肠道组织损伤，影响肠道屏障功能和微生物组成失调，改变宿主代谢，影响消化酶活性，最终影响鱼类生长性能。微塑料暴露以HPG轴为靶点，干扰性腺组织的甾体生成、细胞凋亡过程，最终导致生殖功能障碍。接触微塑料的鱼类具有一系列毒性作用，包括免疫、抗氧化和血液指标的改变、生物蓄积、神经毒性、生长和生殖功能障碍，本文通过不同的指标对这些毒性作用进行了研究。

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引用次数: 0

Natural hemozoin and β-hematin induce tissue damage and apoptosis in human placental explants 天然血红素和β-血红素诱导人胎盘组织损伤和细胞凋亡。

Q1 Environmental Science

Toxicology Reports

Pub Date : 2024-12-08 DOI: 10.1016/j.toxrep.2024.101857

Carolina López-Guzmán , Julieth Herrera , Julián Zapata , Adriana Pabón , Urlike Kemmerling Weis , Ana María Vásquez

Hemozoin (HZ) is a waste product of hemoglobin digestion by Plasmodium and has been implicated in several pathological processes, including inflammation, oxidative stress, endothelial dysfunction, and immune dysregulation. Studying the effects of HZ on the human placenta is essential to understanding the impact of malaria infection during pregnancy. The present study explored the impact of HZ produced by Plasmodium and β-hematin, referred to here as natural HZ (nHZ) and synthetic HZ (sHZ), respectively, on human placental explants exposed in vitro.

Methodology

nHZ was derived from Plasmodium falciparum cultures and isolated using magnetic MACS® Separation Columns (Miltenyi Biotec, Auburn, CA) [1]. sHZ was synthesized from hemin closure in an aqueous solution. Both nHZ and sHZ were characterized by infrared spectroscopy and scanning electron microscopy. Human placental explants (HPE) were exposed to 5 and 10 μg/mL of nHZ and sHZ for 24 h, and tissue integrity was studied using histological and immunohistochemical techniques.

Results

The studies have demonstrated that the exposition of both the nHZ and sHZ to placental tissue are comparable and cause effects in increased STB detachment, dysregulation of collagen distribution in the villous stroma, and increase in the frequency of cell apoptosis. This contributes to the understanding of the pathophysiology of malaria in pregnancy using synthetic products such as β-hematin.

血色素蛋白（HZ）是疟原虫消化血红蛋白的废物，与多种病理过程有关，包括炎症、氧化应激、内皮功能障碍和免疫失调。研究HZ对人胎盘的影响对于了解妊娠期疟疾感染的影响至关重要。本研究探讨了疟原虫和β-血红素产生的HZ(分别称为天然HZ （natural HZ）和合成HZ （synthetic HZ (sHZ)）对体外暴露人胎盘外植体的影响。方法：nHZ来源于恶性疟原虫培养物，采用磁性MACS®分离柱（Miltenyi Biotec, Auburn， CA）[1]进行分离。以血红蛋白闭包为原料，在水溶液中合成了sHZ。用红外光谱和扫描电镜对nHZ和sHZ进行了表征。将人胎盘外植体（HPE）暴露于5和10 μg/mL的nHZ和sHZ中24 h，采用组织学和免疫组织化学技术研究组织完整性。结果：研究表明，nHZ和sHZ对胎盘组织的暴露具有可比性，并导致STB脱落增加，绒毛间质胶原分布失调，细胞凋亡频率增加。这有助于使用合成产品（如β-血素）了解妊娠期疟疾的病理生理学。

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引用次数: 0

Antihypertrophic effects of the seed ethanolic extract of Aframomum pruinosum Gagnep. (Zingiberaceae) against isoproterenol-induced cardiac hypertrophy in male Wistar rat 苦楝种子乙醇提取物的抗肥厚作用。（姜黄科）抗异丙肾上腺素诱导的雄性Wistar大鼠心肌肥厚。

Q1 Environmental Science

Toxicology Reports

Pub Date : 2024-12-07 DOI: 10.1016/j.toxrep.2024.101855

Ariane Falone Goumtsa , Elvine Pami Nguelefack-Mbuyo , Florence Nokam , Cédric Wamba Koho , Cherif Mouhamed Moustapha Dial , Télesphore Benoît Nguelefack

The seeds of Aframomum pruinosum are popularly used in the management of cardiovascular conditions. This study was undertaken to evaluate the capacity of the seed ethanolic extract of A. pruinosum (EE) to prevent the development of cardiac hypertrophy in rats. Isoproterenol (0.3 mg/kg/day, sc) was injected to male rats alone or concomitantly with EE (37.5, 75, or 150 mg/kg, per os) or propranolol (20 mg/kg/day, per os) for 7 consecutive days and systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate measurements were performed. Cardiac homogenates were used to assay myeloperoxidase (MPO), superoxide dismutase (SOD), catalase, nitric oxide (NO) and reduced glutathione (GSH). Also, sections of heart tissue were stained with Hematoxylin-Eosin, Masson trichrome, or for immunohistological labelling of atrial natriuretic peptide (ANP). Isoproterenol administration caused a decline in SBP and DBP (p < 0.001). Heart rate, cardiac mass, cardiomyocyte surface, and MPO levels were significantly (p < 0.001) increased. All these alterations were significantly prevented (p < 0.01 and p < 0.001) by EE. EE inhibited immune cell infiltration and cardiac fibrosis elicited by isoproterenol injection. The overexpression of ANP in the atrium and ventricle induced by the isoproterenol was significantly (p < 0.001) prevented by EE. EE possesses antihypertrophic effect against isoproterenol-induced cardiac hypertrophy that may result from its antifibrotic, anti-inflammatory properties, as well as its capacity to down regulate the expression of ANP.

苦楝种子被广泛用于心血管疾病的治疗。本研究旨在评价猪毛草种子乙醇提取物（EE）对大鼠心肌肥厚的预防作用。将异丙肾上腺素（0.3 mg/kg/天，sc）单独或与EE（37.5、75或150 mg/kg，每os）或心得安（20 mg/kg/天，每os）联合注射给雄性大鼠，连续7天测量收缩压（SBP）、舒张压（DBP）和心率。心脏匀浆检测髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）、过氧化氢酶（过氧化氢酶）、一氧化氮（NO）和还原性谷胱甘肽（GSH）。同时，心脏组织切片用苏木精-伊红染色，马松三色染色，或用于房钠肽（ANP）的免疫组织学标记。异丙肾上腺素引起收缩压和舒张压下降(p

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引用次数: 0

The hepatoprotective effects of the polyphenol-enriched n-butanol fraction of Cnicus benedictus against carbon tetrachloride-induced liver fibrosis in rats: In vivo study 富多酚正丁醇部位对四氯化碳诱导大鼠肝纤维化的保护作用：体内研究。

Q1 Environmental Science

Toxicology Reports

Pub Date : 2024-12-05 DOI: 10.1016/j.toxrep.2024.101850

Mohammed Jasim Mohammed , Haitham Mahmood Kadhim

Liver fibrosis is a continuous wound-healing response to chronic injury caused by various chemical, virus, and pathological disorders; the lack of approved drugs or methods to reverse or prevent liver fibrosis makes it an interesting area of research. This study investigates the potential hepatoprotective effects of the phenolic extract of Cnicus benedictus in rat’s module of liver fibrosis. Liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl₄) for six consecutive weeks; the butanol fraction of Cnicus and silymarin was administered orally concurrently with CCl₄. After six weeks, all animals were euthanized. Rat liver tissue levels of malondialdehyde (MDA) and glutathione (GSH) were measured, and serum liver enzymes and protein were measured using the ELISA technique. Histopathological study and immunohistochemistry of liver tissue for transforming growth factor (TGF-β1), alpha-smooth muscle actin (α-SMA), and hydroxyproline were assessed. In HPLC analysis, Cnicus extract showed several components, including quercetin, gallic acid, rutin, kaempferol, silibinin, and apigenin. Treatment with Cnicus butanol extract reduces serum ALT, AST, bilirubin, and albumin levels compared to induction. Additionally, Cnicus extract increases liver GSH levels and decreases liver MDA levels compared to induction. Liver tissue of TGF-β1, α-SMA, and hydroxyproline expression was downregulated in rats receiving Cnicus extract. Liver tissue histopathology showed improvement in its features compared to the induction group. In conclusion, oral administration of the polyphenol-enriched n-butanol fraction of Cnicus benedictus showed a protective effect on liver fibrosis caused by CCl4, possibly through antioxidant and anti-inflammatory mechanisms.

肝纤维化是对各种化学、病毒和病理性疾病引起的慢性损伤的持续伤口愈合反应；目前还没有批准的药物或方法来逆转或预防肝纤维化，这使得它成为一个有趣的研究领域。本研究探讨了芫花酚提取物对大鼠肝纤维化模型的潜在保护作用。连续6周腹腔注射四氯化碳（CCl4）诱导肝纤维化；山茱萸和水飞蓟素丁醇部分与CCl4同时口服。六周后，所有动物都被安乐死。采用ELISA法测定大鼠肝组织丙二醛（MDA）和谷胱甘肽（GSH）水平，测定血清肝酶和蛋白水平。观察肝组织转化生长因子（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）、羟脯氨酸的组织病理学和免疫组化水平。高效液相色谱法检测出槲皮素、没食子酸、芦丁、山奈酚、水飞蓟宾、芹菜素等主要成分。与诱导治疗相比，丁醇提取物治疗可降低血清ALT、AST、胆红素和白蛋白水平。此外，与诱导相比，蛇麻草提取物增加了肝脏GSH水平，降低了肝脏MDA水平。大鼠肝组织TGF-β1、α-SMA和羟脯氨酸表达下调。与诱导组相比，肝组织病理学显示其特征有所改善。综上所述，口服富多酚正丁醇部位对CCl4所致肝纤维化具有保护作用，可能通过抗氧化和抗炎机制实现。

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