Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in Ppara Transgenic Mice

Metabolites, Journal Year: 2023, Volume and Issue: 13(8), P. 936 - 936

Published: Aug. 10, 2023

Long-term ligand activation of PPARα in mice causes hepatocarcinogenesis through a mechanism that requires functional PPARα. However, is diminished both Ppara-null and PPARA-humanized mice, yet lines develop age-related liver cancer independently treatment with agonist. Since master regulator lipid metabolism the liver, lipidomic analyses were carried out wild-type, Ppara-null, treated without potent agonist GW7647. The levels hepatic linoleic acid markedly higher compared to wild-type controls, along overall fatty liver. number CD4+ T cells was also lower negatively correlated elevated acid. Moreover, more senescent hepatocytes serum TNFα IFNγ observed age. These studies suggest new role for age-associated due altered accumulation as part an associated loss transgenic models. known causal risk factor cancer, are valuable models examining mechanisms age-dependent hepatocarcinogenesis.

Language: Английский

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Serum adiponectin and peroxisome proliferator-activated receptors-γ levels in obese patients with and without prediabetes

Revista da Associação Médica Brasileira, Journal Year: 2024, Volume and Issue: 70(3)

Published: Jan. 1, 2024

Obesity is an increasingly prevalent global health problem, which generally caused by the increase in body fat mass above normal and observed all societies. If blood glucose level higher than but not high enough to diagnose diabetes, this condition defined as prediabetes. Adiponectin increases fatty acid oxidation insulin sensitivity closely associated with obesity. One of nuclear receptor superfamily member peroxisome proliferator-activated receptors shown have important role various metabolic reactions. This study aimed investigate serum levels adiponectin receptors-gamma parameters, are related adipose tissue, energy metabolism, sensitivity, obese patients without

Language: Английский

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Molecular Mechanisms of Clozapine-Induced Pancreatic Damage and its Modulation by L-Carnitine in a Rat Model

Egyptian Society of Clinical Toxicology Journal, Journal Year: 2024, Volume and Issue: 12(1), P. 182 - 199

Published: June 1, 2024

Background: Clozapine (CLZ) has been considered the mainstay drug in treatment of resistant schizophrenia. Diabetes mellitus befallen during clozapine therapy. L-carnitine (LC) protective effects against many health hazards. Aim work: This experiment aimed to examine molecular mechanisms pancreatic insult caused by CLZ rats and possible ameliorating effect LC that toxicity. Material Methods: Thirty-five adult male albino were allocated into five groups equally: control (negative vehicle), LC-treated group received 350 mg/kg/day LC, CLZ-treated gavaged 25 combined LC+CLZ same previous doses. All treatments given orally for 4 weeks. Results: CLZ-treatment triggered a significant rise mean values body weight (BW) serum fasting blood glucose (FBG), amylase, insulin, Triglyceride Glucose (TyG) Index Homeostatic Model Assessment Insulin Resistance (HOMA-IR). Also, upsurge lipid peroxidation pro-inflammatory (Nuclear Factor Kappa-light-chain-enhancer activated B cells (NF-kB)) accompanying decrease catalase (CAT), Hemo oxygenase-1 (HO-1) enzyme nuclear factor erytheroid 2-related (Nrf2) activities anti-inflammatory (IL-10), decreased expression Peroxisome proliferator receptor alfa (PPAR-α) tissues occurred. There was histological immunohistochemical evidence tissue injury with increased collagen fibers. The abnormalities reversed when group. Conclusion: can ameliorate oxidant, inflammatory, apoptotic impacts induced CLZ.

Language: Английский

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In Silico Toxicological Analysis of Active Compounds Present in Selected Pesticides Sold in South-West Nigeria

JURNAL KESEHATAN LINGKUNGAN, Journal Year: 2024, Volume and Issue: 16(3), P. 200 - 212

Published: July 27, 2024

Introduction: The study investigated the molecular effects of human exposure to commonly used pesticides in Nigeria. Methods: Utilizing computational methods like clustering analysis, toxicokinetic predictions, docking, and dynamic (MD) simulation, various health impacts were identified. Results Discussion: results revealed significant gastrointestinal absorption, P-glycoprotein bypass, blood-brain barrier penetration, cytochrome P450 inhibition for certain pesticide agents. Notably, oxathiapiprolin showed hepatotoxicity, propanil exhibited drug-induced liver injury (DILI), 2,4-dichloro-phenoxyacetic acid demonstrated carcinogenicity. Respiratory toxicity was predicted most pesticides, except N-(2,6-diethylphenyl) acetamide. Molecular targets identified, such as bifenthrin targeting programmed cell death 1 ligand Atrazine potassium voltage-gated channel subfamily H member 3. Binding affinities computed, with showing -6.526 kcal/mol short transient receptor potential 7. simulations indicated binding energy changes over time. Atrazine's 3 a total ΔGbind -39.410 -49.135 at 0 ns 100 ns, respectively. Oxathiapiprolin's 7 -53.481 -44.122 ns. Conclusion: This suggests hepatotoxicity carcinogenicity emphasizing need environmental monitoring stringent regulations safeguard public health.

Language: Английский

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Antioxidant effects of a novel pioglitazone analogue (PA9) in a rat model of diabetes: Modulation of redox homeostasis and preservation of tissue architecture

Journal of Diabetes and its Complications, Journal Year: 2024, Volume and Issue: 38(12), P. 108897 - 108897

Published: Oct. 23, 2024

Language: Английский

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Bilirubin, a hepatoprotective agent that activates SIRT1, PGC-1α, and PPAR-α, while inhibiting NF-κB in rats with metabolic-associated fatty liver disease

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 25, 2024

Metabolic-associated fatty liver disease (MAFLD) is a chronic disorder characterized by alongside overweight or obesity and/or type 2 diabetes mellitus (T2DM). Timely intervention crucial for potential cure. This study aimed to investigate the effects of bilirubin, an endogenous antioxidant, on lipid metabolism and inflammation in MAFLD. Specifically, it examined bilirubin's impact SIRT1, PPAR-α, NF-κB livers rats with MAFLD induced high-fat diet (HFD) streptozotocin (STZ) administration. Forty eight-week adult male Sprague Dawley were divided into five groups (n = 8): Control, HFD-STZ, HFD-S-BR6, HFD-S-BR14, C-BR14. In last three groups, bilirubin administration was performed intraperitoneally 6 14 weeks (10 mg/kg/day). We selected key genes associated subsequently GO (Gene Ontology) KEGG (Kyoto Encyclopedia Genes Genomes) analyses explore enriched biological processes signaling pathways. Hence, gene expression PGC-1α, inflammatory (NF-κB, TNF-α, IL-6, IL-1β) measured using Real-time quantitative PCR. Stereological histopathological alterations structure as well profile, biochemical indices, also assessed among different groups. The enrichment analysis identified that several pathways might be related Bilirubin-treated contained higher SIRT1 levels approximately 5.7-, 2.1-, 2.2-fold, respectively, compared HFD-receiving (p < 0.0001, p 0.05, 0.05). Whereas, involved cascades, including NF-κB, downregulated 0.6-fold 0.05) following 14-week treatment while only significantly decreased IL-6 (approximately 0.6-fold, observed after 6-week bilirubin. Remarkably, favorably reversed HFD liver's volume cell numbers ameliorated structural changes. It improved parameters, indices HFD-STZ rats. indicated acts protective/ameliorative compound against MAFLD, particularly through regulating

Language: Английский

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