Jul 2026· Current Bioactive Compounds· Vol 22· 0 citations
TL;DR
LaP-NPs efficiently prevent HgClⁿ-induced lung injury by inhibiting oxidative stress, modulating stress-related genes, and reducing inflammatory pathways, suggesting that LaP-NPs could serve as a nanotherapeutic for heavy metal-induced pulmonary toxicity.
Abstract
Mercuric chloride (HgCl2) is a common environmental toxicant that
causes excessive oxidative stress and inflammation in pulmonary tissue. The present work was
designed to evaluate the protective impact of lapachol nanoparticles (LaP-NPs) on HgCl2-induced
lung toxicity in mice.
LaP-NPs were prepared by nanoprecipitation and characterised for particle size, morphology,
and stability. Adult albino mice were divided into six groups: untreated controls;
LaP-NPs alone; HgCl2 alone; HgCl2 plus LaP-NPs at two doses (21.5 and 53.75 mg/kg); and
HgCl2 plus dexamethasone. All treatments were administered orally for 30 days. Markers of pulmonary
oxidative stress (reduced glutathione [GSH], superoxide dismutase [SOD], glutathione
peroxidase [GPx], and malondialdehyde [MDA]) and inflammatory cytokines were measured.
The gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and protein
39 (P39) were evaluated, and histopathological changes were assessed. Molecular docking
was conducted to investigate possible interactions between lapachol and the Nrf2 and P39 protein
targets.
HgCl2 exposure led to significant oxidative stress, as demonstrated by a significant decline
in GSH, SOD and GPx activities along with increased MDA. This was accompanied by
strong upregulation of IL-1β (+134.7% in plasma), iNOS (+405%), and MIP-1α (+4248%), as
well as robust upregulation of Nrf2 (+570.6%) and P39 (+468.6%) (p < 0.001). High-dose LaPNPs
treatment (53.75 mg/kg) significantly reversed the activity of antioxidant enzymes, decreased
MDA accumulation, and normalised Nrf2 and P39 expression. Several inflammatory mediators
were also significantly suppressed to normal control levels. Histopathological analyses
confirmed the biochemical observations, demonstrating preservation of lung architecture. Also,
docking simulations showed that lapachol had high predicted binding affinities for both Nrf2
(-8.25 kcal/mol) and P39 (-8.06 kcal/mol).
LaP-NPs revealed excellent antioxidant and anti-inflammatory properties, which
were superior to those of native lapachol and comparable to dexamethasone. The nanoformulation
improved the bioavailability and multiple targeting of lapachol, suggesting a potential protective
strategy for heavy-metal-induced lung injury. Limitations are that only one toxicity model
was employed.
LaP-NPs efficiently prevent HgClⁿ-induced lung injury by inhibiting oxidative
stress, modulating stress-related genes, and reducing inflammatory pathways. These findings
suggest that LaP-NPs could serve as a nanotherapeutic for heavy metal-induced pulmonary toxicity.
Man could be considered as a potential protective agent against HgCl2-induced liver injury through controlling oxidative stress, inflammation, and apoptosis.
Hager E Hassan, Sara H. Hazem, M. Zaghloul· Naunyn-Schmiedeberg's Archiv...· 0 citations
Paracetamol is the most common cause of drug- induced liver injury,
which is associated with oxidative stress, cytokine release, and apoptosis. Boswellic acid (BA),
with anti- inflammatory and antioxidant effects, can ameliorate liver injury but has poor solubility
and bioavailability. The objective of this study was to design boswellic acid nanoparticles
(BA-NPs) and test their protective effect against paracetamol-induced liver injury in mice.
BA-NPs were prepared by a surfactant-assisted emulsion method and characterized by
UV-Vis spectroscopy, FT-IR analysis, dynamic light scattering (DLS), zeta potential measurements,
and transmission electron microscopy (TEM). Acute oral toxicity (LD₂⁽) was assessed in
healthy mice. Liver- intoxicated mice were treated with paracetamol (1 g/kg, po) and pretreated
for 14 days with BA- NPs (75 mg/kg, po) or silymarin (50 mg/kg). Measurements included serum
liver enzymes (ALT, AST, and ALP), lipid profile markers (TC, TG, and HDL), oxidative
stress indicators (GSH, CAT, GPx, SOD, and MDA), inflammatory cytokines and their markers
(IL- 6 and TNF–α), the apoptotic marker p 53, caspase- 8 and STAT 3 mRNA expression measured
by qPCR, and molecular docking simulations to predict boswellic acid's binding affinity to
target proteins.
The formulated BA- NPs were spherical and monodisperse (54. 54.54 ± 2. 76 nm) with
colloidal stability (zeta potential:- 18. 84 mV; PDI: 0. 26). The LD50 was estimated to be 1500
mg/kg, indicating relatively low acute toxicity. BA-NP pretreatment alleviated paracetamolinduced
increases in ALT, AST, and ALP; normalized dyslipidemia; restored antioxidant activity;
and decreased MDA levels. We observed that the levels of pro- inflammatory cytokines (IL-
6, TNF- α) and p 53 were strongly downregulated. The expression of both caspase-8 and STAT3
was also downregulated by BA-NPs. Molecular docking data showed that boswellic acid bound
significantly to caspase-8 (ΔG = -7.97 kcal/mol) and STAT3 (ΔG = -7.95 kcal/mol), supporting
its mechanism of hepatoprotection.
Our results indicate that BA- NPs prepared by Span 60/Tween 80 emulsification
provide potent hepatoprotection against paracetamol- induced liver injury through synergistic,
multi- mechanistic action, significantly protecting against hepatic injury by concurrently suppressing
oxidative stress, inflammatory signaling pathways, and apoptosis, three interconnected
molecular events critical to the pathogenesis of paracetamol hepatotoxicity.
BA-NPs prepared via emulsification of Span 60/Tween 80 offer potent hepatoprotection
against paracetamol-induced liver injury by primarily modulating oxidative stress, inflammation,
and apoptosis. This approach not only highlights a potentially novel therapeutic for
drug- induced hepatotoxicity but also overcomes the pharmacokinetic barriers of the native boswellic
acid agent and provides an improved alternative to currently available drugs.
Ola Abdallah Ahmed, M. Hussein, Azza Mahmoud Abdullah· The Natural Products Journal· 0 citations
Arsenic trioxide (ATO) is a potent therapeutic agent against acute promyelocytic leukemia; nevertheless, its clinical utility is severely restricted by dose-limiting nephrotoxicity. This study investigated the protective potential of a radiation-synthesized gallotannin hydrogel (GTH) against ATO-induced kidney injury in rats. Forty male Wistar rats were randomized into four experimental groups: Control, ATO (4 mg/kg, i.p., for 4 weeks), GTH (2 mg/kg, i.p.), and ATO + GTH. GTH treatment was initiated during the third week of ATO administration, with GTH being administrated one hour prior to ATO injection. Following the experimental period, animals were sacrificed, tissue histology was examined, and renal function was assessed by serum urea and creatinine levels. Oxidative stress was evaluated via MDA, SOD, GSH, and GPx markers. Additionally, miR-223 and TXNIP expression levels were quantified using qRT-PCR. Inflammatory mediators (NF-κB, NLRP3, Caspase-1, IL-1β, and IL-18), endoplasmic reticulum (ER) stress markers (PERK, eIF2α, and CHOP), and the apoptotic marker caspase-3 were analyzed by ELISA. Our results revealed that GTH noticeably ameliorated kidney dysfunction, as evidenced by reduced serum urea and creatinine levels. Furthermore, GTH attenuated oxidative stress by decreasing MDA levels and restoring antioxidant enzyme activities (SOD, GSH, and GPx). Histological analysis confirmed that GTH mitigated structural renal damage. Molecularly, GTH administration suppressed the ATO-induced upregulation of miR-223 and TXNIP. This downregulation correlated with a reduction in inflammatory mediators, attenuation of ER stress markers, and decreased apoptosis. These findings demonstrate that radiation-synthesized gallotannin hydrogel (GTH) exerts nephroprotective effects against ATO-induced nephrotoxicity. These benefits are driven by antioxidant, anti-inflammatory, and anti-apoptotic mechanisms mediated via modulation of the miR-223/TXNIP axis.
Omayma A. R. Abo-Zaid, Mostafa A. Farrag, Aya S. R. Shaaban et al.· Biological Trace Element Res...· 0 citations
Overall, nano-liposomal delivery enhanced the renoprotective efficacy of limonene, highlighting its potential as a therapeutic strategy against pesticide-induced kidney injury.
E. Elmorsy, Amina A. Farag, Amal M. Abdel-Kareim et al.· Toxics· 0 citations
Polystyrene nanoplastics (PS-NPs) are emerging food safety contaminants. Ferroptosis is iron-dependent cell death, but its role in PS-NPs hepatotoxicity is unclear. Mice received tail-vein injection of PS-NPs (2-8mg/kg). PS-NPs caused liver injury (elevated transaminases) and possible renal impairment (increased uric acid/creatinine/urea). Hepatic GSH and SOD decreased, IL-1β and TNF-α increased. Mitochondrial shrinkage and cristae loss (ferroptotic features) were observed. PS-NPs upregulated ACSL4, MDA, 4-HNE and TfR, but suppressed FTH1, FPN1, SLC7A11 and GPx4. Thus, ferroptosis mediates PS-NPs liver injury with oxidative stress and inflammation, and PS-NPs may exert multi-organ toxicity.
Ci Ou, Hanpeng Wu, Yichun Chen et al.· Toxicology Letters· 0 citations
