Olmutinib Reverses Thioacetamide-Induced Cell Cycle Gene Alterations in Mice Liver and Kidney Tissues, While Wheat Germ Treatment Exhibits Limited Efficacy at Gene Level DOI Creative Commons
Seema Zargar, Tanveer A. Wani,

Salman Alamery

et al.

Medicina, Journal Year: 2024, Volume and Issue: 60(4), P. 639 - 639

Published: April 16, 2024

Background and Objectives: TAA is potent hepatic/renal toxicant. Conversely, WGO a dietary supplement with impressive antioxidant properties. Olmutinib an apoptotic chemotherapy drug that does not harm the liver or kidney. This study investigated impact of olmutinib wheat germ oil (WGO) on Thioacetamide (TAA)-induced gene alterations in mice kidney tissues. Materials Methods: Adult male C57BL/6 were exposed to 0.3% drinking water for 14 days, followed by oral administration (30 mg/kg) (1400 5 consecutive days. Treatment groups included following: I (control), II (TAA-exposed), III (TAA + olmutinib), IV WGO), V WGO). Results: The findings revealed exposure increased MKi67 CDKN3 expression treatment effectively reversed these TAA-induced effects, significantly restoring expression. also effects but exhibited limited efficacy reversing induced exposures both showed tissue-specific TP53, decreased TP53 While alone could reverse exposure, co-administration remarkable potentiation therapeutic interaction analysis 77.4% physical interactions co-localization between MKi67, CDKN3, expressions. Protein–protein networks demonstrated forming complexes signaling cascades. Conclusions: It was predicted leads increase which negatively regulates cell cycle via kidneys restoration levels liver. These contribute our understanding changes highlight their contrasting based alterations.

Language: Английский

Ginsenoside Rd protects against acute liver injury by regulating the autophagy NLRP3 inflammasome pathway DOI Creative Commons
Xiaomei Zhong,

Yibin Sun,

Yanxiang Lin

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 28, 2025

Ginsenoside Rd (Rd) is a bioactive compound predominantly found in Panax ginseng C.A. Meyer and notoginseng (Burkill) F.H. Chen ex C.H. Chow, both species belonging to genus the Araliaceae family. However, its hepatic protective effect against acute liver injury related mechanistic action remain unexplored. To investigate of thioacetamide (TAA)-induced assess underlying regulatory mechanisms autophagy inflammation. Forty-eight 8 weeks old C57BL/6 mice were treated with saline (control or model group), (12.5 mg/kg, 25 mg/kg 50 mg/kg), diammonium glycyrrhizinate (DG, 30 mg/kg) for three days. Then stimulated TAA establish model, excluding control group. HSC-T6 cells at concentrations 2.5, 5, 10 µM, 12 h without Lipopolysaccharide (LPS) stimulation 100 ng/mL. Immunofluorescence staining, qPCR Western blot employed analyze expressions genes proteins associated inflammation autophagy. validate role regulating inflammation, inducers, rapamycin GSK621, utilised reverse validation experiments cells. exhibited significant effects by reducing serum levels Aspartate aminotransferase (AST), Alanine (ALT), Glutathione S-transferase (GST) Lactate dehydrogenase (LDH) injury. It strong anti-inflammatory protein, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nod-like receptor protein 3 (NLRP3), speck-like containing CARD (ASC), interleukin-18 (IL-18) interleukin-1β(IL-1β) mRNA expression COX-2, Tumor Necrosis Factor α (TNF α), interleukin-6 (IL-6) iNOS decreased tissue. And inhibited LPS-induced COX-2 NLRP3 Moreover, not only vivo but also vitro, downregulated LC3II, Beclin1, phosphorylation-AMP-activated kinase (p-AMPK), phosphorylation-ULK1 (p-ULK1) upregulated p62 phosphorylation-mechanistic target (p-mTOR) suppress via AMPK/mTOR/ULK1 pathway. Finally, inhibitory on partially blocked GSK621. promising therapeutic agent protect TAA-induced autophagy-NLRP3 inflammasome

Language: Английский

Citations

1
Albiflorin ameliorates thioacetamide-induced hepatic fibrosis: The involvement of NURR1-mediated inflammatory signaling cascades in hepatic stellate cells activation DOI Creative Commons
Jian Song,

Bo-Feng Qin,

Qi-Yuan Feng

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 276, P. 116334 - 116334

Published: April 15, 2024

Thioacetamide (TAA) within the liver generates hepatotoxic metabolites that can be induce hepatic fibrosis, similar to clinical pathological features of chronic human disease. The potential protective effect Albiflorin (ALB), a monoterpenoid glycoside found in Paeonia lactiflora Pall, against fibrosis was investigated. mouse model induced with an intraperitoneal injection TAA. Hepatic stellate cells (HSCs) were subjected treatment transforming growth factor-beta (TGF-β), while lipopolysaccharide/adenosine triphosphate (LPS/ATP) added stimulate peritoneal macrophages (MPMs), leading acquisition conditioned medium. For TAA-treated mice, ALB reduced ALT, AST, HYP levels serum or liver. administration histopathological abnormalities, and significantly regulated expressions nuclear receptor-related 1 protein (NURR1) P2X purinoceptor 7 receptor (P2×7r) could suppress HSCs epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, pro-inflammatory factor level. also remarkably up-regulated NURR1, inhibited P2×7r signaling pathway, worked as working C-DIM12, NURR1 agonist. Moreover, deficiency activated Kupffer weakened regulatory on inhibition. NURR1-mediated inhibition inflammatory contributed regulation ameliorates TAA-induced especially based involving crosstalk HSCs-macrophage. Therefore, plays significant part mitigation hepatotoxicity this highlights intervention for fibrosis.

Language: Английский

Citations

6
Echinacoside ameliorates hepatic fibrosis and tumor invasion in rats with thioacetamide-induced hepatocellular carcinoma DOI Creative Commons
Ajwan Z Albalawi, Areej S. Alatawi,

Shekha M. Al-Atwi

et al.

Biomolecules and Biomedicine, Journal Year: 2024, Volume and Issue: 24(5), P. 1186 - 1198

Published: March 10, 2024

Hepatocellular carcinoma (HCC) affects approximately 800,000 individuals globally each year. Despite advancements in HCC treatments, there is still a pressing need to identify new drugs that can combat resistance. One potential option echinacoside, natural caffeic acid glycoside with antioxidant, anti-inflammatory, antidepressant, and antidiabetic properties. Therefore, we aimed investigate the ability of echinacoside exhibit antitumor activity against rats through ameliorating hepatic fibrosis tumor invasion. Rats were given thioacetamide induce HCC, some 30 mg/kg twice week for 16 weeks. The liver impairment was assessed by measuring serum α-fetoprotein (AFP) examining sections stained Masson trichrome or anti-transforming growth factor (TGF)-β1 antibodies. expression mRNA protein levels TGF-β1, β-catenin, SMAD4, matrix metalloproteinase-9 (MMP9), phosphoinositide 3-kinases (PI3K), mammalian target rapamycin (mTOR), connective tissue 2 (CCN2), E-Cadherin, platelets derived (PDGF)-B fascin also analyzed. Echinacoside improved survival rate decreasing AFP number nodules. Examination micro-images indicated reduce fibrosis. It significantly decreased MMP9, PI3K, mTOR, CCN2, PDGF-B, while enhancing E-Cadherin. In conclusion, exhibits protective effect increasing rates growth. acts as an inhibitor pathway reducing PDGF-B mTOR. Additionally, it prevents invasion suppressing MMP9 fascin,

Language: Английский

Citations

5
The Role of Selenium Nanoparticles in the Treatment of Liver Pathologies of Various Natures DOI Open Access
M. V. Goltyaev, Elena G. Varlamova

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10547 - 10547

Published: June 23, 2023

The liver is the body’s largest gland, and regulates a wide variety of physiological processes. work can be disrupted in pathologies, number which several hundred. It extremely important to monitor health develop approaches combat diseases. In recent decades, nanomedicine has become increasingly popular treatment various nanosized biomaterials, are inorganic, polymeric, liposomal, albumin, other nanoparticles, play an role. Given need environmentally safe, inexpensive, simple, high-performance biomedical agents for theragnostic purposes showing few side effects, special attention being paid nanoparticles based on trace element selenium (Se). known that metabolism microelement Se occurs liver, its deficiency leads development serious diseases this organ. addition, depot most selenoproteins, reduce oxidative stress, inhibit tumor growth, prevent damage. This review devoted description results years, revealing role therapy diagnosis depending dose physicochemical properties. possibilities diseases, disclosed review, will not only reveal advantages their hepatoprotective properties but also significantly supplement data regulation these

Language: Английский

Citations

12
Hepatoprotective impact of Nigella sativa silver nanocomposite against genotoxicity, oxidative stress, and inflammation induced by thioacetamide DOI
Fatma M. El‐Demerdash,

Ansam B. Al Mhanna,

Mohammed A. El‐Magd

et al.

Tissue and Cell, Journal Year: 2024, Volume and Issue: 87, P. 102332 - 102332

Published: Feb. 15, 2024

Language: Английский

Citations

4
Lactoferrin as a therapeutic agent for attenuating hepatic stellate cell activation in thioacetamide-induced liver fibrosis DOI Creative Commons
Tzu-Yu Pu, Kai-Cheng Chuang, Min‐Che Tung

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116490 - 116490

Published: March 29, 2024

Liver fibrosis is a chronic liver disease caused by prolonged injuries. Excessive accumulation of extracellular matrix replaces the damaged hepatocytes, leading to fibrous scar formation and induction. Lactoferrin (LF) glycoprotein with conserved, monomeric signal polypeptide chain, exhibiting diverse physiological functions, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, antitumoral activities. Previous study has shown LF's protective role against chemically-induced in rats. However, mechanisms LF are still unclear. In this study, we investigated thioacetamide (TAA)-induced rats TGF-β1-treated HSC-T6 cells. Using ultrasonic imaging, H&E, Masson's, Sirius Red staining, demonstrated ability improve tissue damage induced TAA. reduced levels ALT, AST, hydroxyproline TAA-treated tissues, while increasing catalase levels. Additionally, treatment decreased mRNA expression inflammatory factors such as Il-1β Icam-1, well fibrogenic α-Sma, Collagen I, Ctgf tissues. Furthermore, TAA-induced ROS production cell death FL83B cells, α-SMA, p-Smad2/3 productions Our highlights ameliorate hepatocyte damage, oxidative stress, rats, potentially through its inhibitory effect on HSC activation. These findings suggest potential therapeutic agent for protecting injuries fibrosis.

Language: Английский

Citations

4
Silymarin and MSC-exosomes ameliorate thioacetamide-evoked renal fibrosis by inhibiting TGF-β/SMAD pathway in rats DOI Creative Commons

Dina Mohamed Mekawy,

Dina Sabry, Rania Mohamed Sabry

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: April 18, 2024

Abstract Background TGF-β1 and SMAD3 are particularly pathogenic in the progression of renal fibrosis. Aim This study aimed to evaluate kidney protective potentials silymarin (SM) exosomes mesenchymal stem cells against nephrotoxin thioacetamide (TAA) rats. Methods 32 female rats were randomly assigned into four groups: control group, TAA + SM Exosomes group. The homogenates from all groups examined for expression levels TGF-β receptors I II using real-time PCR, collagen type CTGF proteins ELISA, nuclear SMAD2/3/4, cytoplasmic SMAD2/3, SMAD4 western blot technique. Results Compared injection resulted a significant increase serum urea creatinine, gene TβRI TβRII, protein both proteins, SMAD2/3 complex, SMAD2/3/4 (p-value < 0.0001), with significantly decreased co-SMAD partner, 0.0001). Those effects reversed considerably treatment groups, superiority exosomal regarding SMAD gene, I, returning near-control values > 0.05). Conclusion Using vitro vivo experimental approaches, research discovered reno-protective role BM-MSCs after thioacetamide-induced fibrosis rats, advantage exosomes.

Language: Английский

Citations

3
Investigating the Effect and Potential Mechanism of Rhamnetin 3-O-α-Rhamnoside on Acute Liver Injury In Vivo and In Vitro DOI Creative Commons

Dandan Deng,

Binghao Zhao, Hong Yang

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 116 - 116

Published: Jan. 17, 2025

Background/Objectives: Rhamnetin 3-O-α-rhamnoside (ARR) is a major flavonoid of the herb Loranthus tanakae Franch. & Sav., which has been used for treating liver diseases in China. However, protective effect ARR on not reported. Methods: Zebrafish larvae were as visual animal model, and injury was induced by thioacetamide (TAA) an acute (ALI) model. The hepatoprotective activity evaluated assessing morphology, function indices, oxidative stress, mRNA expression levels inflammation-related genes zebrafish Additionally, ROS level, inflammatory factors, protein related to IKKβ/NF-κB signaling pathway measured investigate potential mechanism HepG2 cells. Results: ameliorated TAA-induced growth retardation, reduced phenotypes, decreased stress zebrafish. also able lower cells, effectively inhibit overactivation pathological conditions, NF-κB p65 translocation from cytoplasm nucleus, reduce release intracellular factors. Conclusions: showed significant against vivo vitro models, its closely pathway.

Language: Английский

Citations

0
Differentiation-inducing factor-1 ameliorates liver fibrosis through the reversion of activated hepatic stellate cells DOI
Akira Ooka, Momoka Yamaguchi, Kensuke Suzuki

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(5), P. 167802 - 167802

Published: March 17, 2025

Language: Английский

Citations

0
Acute toxicity and hepatoprotective effect of Arum maculatum on rat liver cirrhosis induced with thioacetamide DOI Creative Commons
Riyadh Zainadin Mawlood, Kamaran Abdoulrahman

Acta Pharmaceutica, Journal Year: 2025, Volume and Issue: 75(1), P. 87 - 102

Published: March 1, 2025

Abstract Arum maculatum is a medicinal plant that has been employed in traditional medicine for treating liver diseases. The objective of the current study was to evaluate hepatoprotective impacts ethanolic extract A. leaves on cirrhosis induced by thioacetamide (TAA) Sprague--Dawley rats. rats were treated two months with administered intraperitoneally thrice weekly. Histopathological examination revealed severe damage control group, while silymarin treatments ( p < 0.05). Furthermore, treatment led normalization pro-inflammatory cytokines TNF-α and IL-6, increased expression anti-inflammatory cytokine IL-10 Thus, might have role rat TAA, along antioxidant effects.

Language: Английский

Citations

0