Enhancement of biochemical and genomic pathways through lycopene-loaded nano-liposomes: Alleviating insulin resistance, hepatic steatosis, and autophagy in obese rats with non-alcoholic fatty liver disease: Involvement of SMO, GLI-1, and PTCH-1 genes

Salem, Gamal A.; Mohamed, Amany Abdel-Rahman; Khater, Safaa I.; Noreldin, Ahmed E.; Alosaimi, Manal E.; Alansari, Wafa S.; Shamlan, Ghalia; Eskandrani, Areej A.; Awad, Marwa Mahmoud; El-Shaer, Rehab Ahmed Ahmed; Nassan, Mohamed A.; Mostafa, Mahmoud; Khamis, Tarek

doi:10.1016/j.gene.2023.147670

Cited by 12 publications

(6 citation statements)

References 130 publications

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“…It was shown that IMI upregulated pancreatic immunohistochemical expression of NLRP3 and elevated the levels of caspase-1 in rats exposed to IMI alone compared to unexposed rats. Previous studies have indicated that IMI induces hepatic and renal tissue pyroptosis by increasing the expression of pyroptotic biomarkers, including NLRP3 and caspase 1, which would be consistent with our results [25,26].…”

Section: Discussionsupporting

confidence: 93%

“…Previous investigations have demonstrated that this dose is effective in producing antioxidant defence and reducing the toxicity of certain xenobiotics [19][20][21][22][23][24]. -Group III: Rats were treated with IMI at a dose of 45 mg/kg, which is 1/10 of the LD50 [25][26][27]. -Group IV: Rats were treated with a combination of IMI (45 mg/kg) and LYC (10 mg/kg).…”

Section: Experimental Designmentioning

confidence: 99%

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Role of IRE1α/XBP1/CHOP/NLRP3 Signalling Pathway in Neonicotinoid Imidacloprid-Induced Pancreatic Dysfunction in Rats and Antagonism of Lycopene: In Vivo and Molecular Docking Simulation Approaches

El Gazzar,

Bayoumi,

Youssef

et al. 2024

Toxics

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Imidacloprid (IMI) is a commonly used new-generation pesticide that has numerous harmful effects on non-targeted organisms, including animals. This study analysed both the adverse effects on the pancreas following oral consumption of imidacloprid neonicotinoids (45 mg/kg daily for 30 days) and the potential protective effects of lycopene (LYC) administration (10 mg/kg/day for 30 days) with IMI exposure in male Sprague–Dawley rats. The apoptotic, pyroptotic, inflammatory, oxidative stress, and endoplasmic reticulum stress biomarkers were evaluated, along with the histopathological alterations. Upon IMI administration, noticeable changes were observed in pancreatic histopathology. Additionally, elevated oxidative/endoplasmic reticulum-associated stress biomarkers, inflammatory, pyroptotic, and apoptotic biomarkers were also observed following IMI administration. LYC effectively reversed these alterations by reducing oxidative stress markers (e.g., MDA) and enhancing antioxidant enzymes (SOD, CAT). It downregulated ER stress markers (IRE1α, XBP1, CHOP), decreased pro-inflammatory cytokines (TNF-α, IL-1β), and suppressed pyroptotic (NLRP3, caspase-1) along with apoptotic markers (Bax, cleaved caspase-3). It also improved the histopathological and ultrastructure alterations brought on by IMI toxicity.

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Section: Discussionsupporting

confidence: 93%

Section: Experimental Designmentioning

confidence: 99%

Role of IRE1α/XBP1/CHOP/NLRP3 Signalling Pathway in Neonicotinoid Imidacloprid-Induced Pancreatic Dysfunction in Rats and Antagonism of Lycopene: In Vivo and Molecular Docking Simulation Approaches

El Gazzar,

Bayoumi,

Youssef

et al. 2024

Toxics

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“…Dysregulation in these genes can further exacerbate ROS production, creating a vicious cycle of oxidative stress. This cascade of events ultimately activates apoptotic pathways, initiating programmed cell death ( Cao et al, 2007 ; Salem et al, 2023 ). Environmental toxicants can cause PD by disrupting mitochondrial function or dynamics ( Arya et al, 2018 ; Khater et al, 2021 ; Yin et al, 2021 ; Lin et al, 2022 ) regulated by Mfn1 , Mfn2, and Drp1 genes ( Gassner et al, 1997 ; Reddy et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring the link between pyrethroids exposure and dopaminergic degeneration through morphometric, immunofluorescence, and in-silico approaches: the therapeutic role of chitosan-encapsulated curcumin nanoparticles

Alotaibi,

Abdel-Rahman Mohamed,

Abd-Elhakim

et al. 2024

Front. Pharmacol.

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Introduction: The synthetic pyrethroid derivative fenpropathrin (FNE), a commonly used insecticide, has been associated with various toxic effects in mammals, particularly neurotoxicity. The study addressed the hallmarks of the pathophysiology of Parkinson’s disease upon oral exposure to fenpropathrin (FNE), mainly the alteration of dopaminergic markers, oxidative stress, and molecular docking in rat models. In addition, the protective effect of curcumin-encapsulated chitosan nanoparticles (CRM-Chs-NPs) was also assessed. Methods: In a 60-day trial, 40 male Sprague Dawley rats were divided into 4 groups: Control, CRM-Chs-NPs (curcumin-encapsulated chitosan nanoparticles), FNE (15 mg/kg bw), and FNE + CRM-Chs-NPs. Results: FNE exposure induced reactive oxygen species generation, ATP production disruption, activation of inflammatory and apoptotic pathways, mitochondrial function and dynamics impairment, neurotransmitter level perturbation, and mitophagy promotion in rat brains. Molecular docking analysis revealed that FNE interacts with key binding sites of dopamine synthesis and transport proteins. On the other hand, CRM-Chs-NPs mitigated FNE’s toxic effects by enhancing mitochondrial dynamics, antioxidant activity, and ATP production and promoting anti-inflammatory and antiapoptotic responses.Conclusion: In summary, FNE appears to induce dopaminergic degeneration through various mechanisms, and CRM-Chs-NPs emerged as a potential therapeutic intervention for protecting the nervous tissue microenvironment.

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“…The solvent injection method was utilized to produce chrysin-loaded PEGylated liposomes (Chr-PLs), as described elsewhere [ 35 , 36 ]. To develop the organic phase, saturated phosphatidylcholine from soybean, cholesterol, chrysin, and PEG 4000 were added to 100% ethyl alcohol in the following proportions: 13:3:1:1 (w/w).…”

Section: Methodsmentioning

confidence: 99%

“…Particle size diameter, polydispersity score, zeta potential, transmission electron microscope (TEM), and an in vitro release study were all used to characterize the newly generated Chr-PLs formulation. The produced liposomal suspension's particle size diameter, polydispersity score, and zeta potential were measured using the Malvern Zetasizer Nano (Malvern Instruments Ltd., Worcestershire, UK) as previously reported [ 35 , 38 ]. After the liposomal systems were lysed, the entrapment efficiency of the resulting systems was assessed, as previously reported [ 39 ].…”

Section: Methodsmentioning

confidence: 99%

Chrysin-loaded PEGylated liposomes protect against alloxan-induced diabetic neuropathy in rats: the interplay between endoplasmic reticulum stress and autophagy

Abd El-Emam,

Behairy,

Mostafa

et al. 2024

Biol Res

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Background Diabetic neuropathy (DN) is recognized as a significant complication arising from diabetes mellitus (DM). Pathogenesis of DN is accelerated by endoplasmic reticulum (ER) stress, which inhibits autophagy and contributes to disease progression. Autophagy is a highly conserved mechanism crucial in mitigating cell death induced by ER stress. Chrysin, a naturally occurring flavonoid, can be found abundantly in honey, propolis, and various plant extracts. Despite possessing advantageous attributes such as being an antioxidant, anti-allergic, anti-inflammatory, anti-fibrotic, and anticancer agent, chrysin exhibits limited bioavailability. The current study aimed to produce a more bioavailable form of chrysin and discover how administering chrysin could alter the neuropathy induced by Alloxan in male rats. Methods Chrysin was formulated using PEGylated liposomes to boost its bioavailability and formulation. Chrysin PEGylated liposomes (Chr-PLs) were characterized for particle size diameter, zeta potential, polydispersity index, transmission electron microscopy, and in vitro drug release. Rats were divided into four groups: control, Alloxan, metformin, and Chr-PLs. In order to determine Chr- PLs’ antidiabetic activity and, by extension, its capacity to ameliorate DN, several experiments were carried out. These included measuring acetylcholinesterase, fasting blood glucose, insulin, genes dependent on autophagy or stress in the endoplasmic reticulum, and histopathological analysis. Results According to the results, the prepared Chr-PLs exhibited an average particle size of approximately 134 nm. They displayed even distribution of particle sizes. The maximum entrapment efficiency of 90.48 ± 7.75% was achieved. Chr-PLs effectively decreased blood glucose levels by 67.7% and elevated serum acetylcholinesterase levels by 40% compared to diabetic rats. Additionally, Chr-PLs suppressed the expression of ER stress-related genes (ATF-6, CHOP, XBP-1, BiP, JNK, PI3K, Akt, and mTOR by 33%, 39.5%, 32.2%, 44.4%, 40.4%, 39.2%, 39%, and 35.9%, respectively). They also upregulated the miR-301a-5p expression levels by 513% and downregulated miR-301a-5p expression levels by 65%. They also boosted the expression of autophagic markers (AMPK, ULK1, Beclin 1, and LC3-II by 90.3%, 181%, 109%, and 78%, respectively) in the sciatic nerve. The histopathological analysis also showed that Chr-PLs inhibited sciatic nerve degeneration. Conclusion The findings suggest that Chr-PLs may be helpful in the protection against DN via regulation of ER stress and autophagy. Graphical Abstract

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Enhancement of biochemical and genomic pathways through lycopene-loaded nano-liposomes: Alleviating insulin resistance, hepatic steatosis, and autophagy in obese rats with non-alcoholic fatty liver disease: Involvement of SMO, GLI-1, and PTCH-1 genes

Cited by 12 publications

References 130 publications

Role of IRE1α/XBP1/CHOP/NLRP3 Signalling Pathway in Neonicotinoid Imidacloprid-Induced Pancreatic Dysfunction in Rats and Antagonism of Lycopene: In Vivo and Molecular Docking Simulation Approaches

Role of IRE1α/XBP1/CHOP/NLRP3 Signalling Pathway in Neonicotinoid Imidacloprid-Induced Pancreatic Dysfunction in Rats and Antagonism of Lycopene: In Vivo and Molecular Docking Simulation Approaches

Exploring the link between pyrethroids exposure and dopaminergic degeneration through morphometric, immunofluorescence, and in-silico approaches: the therapeutic role of chitosan-encapsulated curcumin nanoparticles

Chrysin-loaded PEGylated liposomes protect against alloxan-induced diabetic neuropathy in rats: the interplay between endoplasmic reticulum stress and autophagy

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