Jun 2026· Uttar Pradesh Journal of Zoology· Vol 47, pp. 204-213· 0 citations
TL;DR
Findings indicate that acute oral exposure to 1-butyl-3-methylimidazolium hydroxide at its LD50 dose disturbed hepatic antioxidant enzyme activity and induced time-dependent DNA damage in mouse liver tissue.
Abstract
Ionic liquids (ILs), particularly imidazolium-based compounds, are increasingly used in industrial and technological processes because of their distinctive physicochemical properties. However, concerns remain regarding their possible toxicological effects in biological systems. The present study investigated the acute hepatotoxic and genotoxic effects of 1-butyl-3-methylimidazolium hydroxide ([Bmim]OH) in female albino mice (Mus musculus). Acute toxicity testing was performed to determine the median lethal dose (LD50) of [Bmim]OH, and the calculated LD50 value of 18,197 mg/kg body weight was administered orally to experimental mice. Animals were divided into control and treatment groups, and liver tissues were collected after 12 and 24 h of exposure. Hepatic oxidative stress was assessed by measuring the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), while genotoxicity was evaluated using hepatic DNA damage analysis. The results showed that SOD activity increased slightly after 12 h and significantly after 24 h of exposure (75.30 ± 2.82 U/mg protein; p < 0.001) compared with the control group (66.98 ± 2.43 U/mg protein). In contrast, CAT activity decreased significantly after 24 h (17.69 ± 1.54 U/mg protein; p < 0.001), and GPx activity also declined significantly after 24 h (64.46 ± 2.31 U/mg protein; p < 0.001). No significant changes were observed after the shorter exposure period. The comet assay showed no significant DNA damage after 12 h of exposure, whereas the Olive tail moment increased significantly after 24 h (0.8050 ± 0.052; p < 0.05). These findings indicate that acute oral exposure to [Bmim]OH at its LD50 dose disturbed hepatic antioxidant enzyme activity and induced time-dependent DNA damage in mouse liver tissue.
It is suggested that EHDPP may enhance protein expression of hepatic Cyp1a1, Cyp2e1, AhR and PXR and induce liver damage and DNA/chromosome damage in mice; Cyp1a1 might be a major activating enzyme.
Zhao Zhou, Hongbin Gao, Shunda Zhu et al.· Toxics· 0 citations
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.
Azza M. Metwaly, M. Eldeeb, M. Hussein et al.· Current Bioactive Compounds· 0 citations
ABSTRACT Introduction: Toxic hepatitis is characterized by enhanced oxidative stress and disruption of antioxidant defense mechanisms in the liver mitochondria. In this study, we investigated the effects of polyphenolic extracts (Helmar-1 and Helmar-2) obtained from Helichrysum maracandicum on mitochondrial antioxidant systems in rats with experimentally induced toxic hepatitis. Methods: Experimental toxic hepatitis was established in rats through intraperitoneal administration of carbon tetrachloride (CCl₄) diluted in olive oil (50%, 1 mL/kg), administered twice weekly over a two-week period. Liver injury was verified by elevated plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The animals were subsequently treated with Helmar-1 and Helmar-2 extracts at a dose of 20 mg/kg per day for 10 consecutive days. The activities of key antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), malondialdehyde (MDA) content, and mitochondrial respiration and oxidative phosphorylation parameters (V₂, V₃, V₄, RCR, and ADP/O ratio) were assessed in liver mitochondria. Results: Treatment with both Helmar-1 and Helmar-2 extracts resulted in a significant enhancement of antioxidant enzyme activities, a marked reduction in MDA levels, and substantial improvement in mitochondrial respiration and oxidative phosphorylation parameters compared to untreated toxic hepatitis groups. Conclusion: Overall, these results confirm that Helichrysum maracandicum polyphenol extracts improve mitochondrial respiration, oxidative phosphorylation efficiency, antioxidant defense, and membrane stability in toxic hepatitis.
S. Ahmedova, M. Asrarov, S. Mirzakulov et al.· Drug Target Insights· 0 citations
Findings provide mechanistic evidence for the protective effects of NZ-419 and support its potential as a renoprotective agent against oxidative stress-related kidney injury.
E. Ofori-Attah, Mai Hashimoto, Mayu Oki et al.· Clinical and Experimental Ne...· 0 citations
Acrylamide (Acr) is a widely encountered environmental and dietary toxicant known to induce oxidative stress and disrupt male reproductive function. Leydig cells, due to their high metabolic activity and mitochondrial dependence, are particularly vulnerable to redox imbalance. N-acetylcysteine (Nac), a thiol-containing antioxidant and glutathione precursor, has been extensively studied for its cytoprotective properties. However, its modulatory effects on Acr-induced toxicity in Leydig cells and its pharmacodynamic interaction profile remain incompletely characterized. In this study, TM3 Leydig cells were exposed to Acr in the presence or absence of Nac. Cell viability was assessed by MTT assay, and chemical interaction profiles were evaluated using ZIP, Bliss, and Chou-Talalay combination index analyses. Oxidative stress parameters, including intracellular reactive oxygen species (ROS), lipid peroxidation, antioxidant enzyme activities (SOD, CAT, GPx), and glutathione levels, were measured. Apoptotic responses were analyzed through double fluorescence staining, RT-qPCR of apoptosis-related genes (Bax, Bcl2, Casp3, Trp53), and Western blot analysis of CASP3 protein expression. Acr exposure significantly reduced cell viability, increased ROS and lipid peroxidation levels, suppressed antioxidant defenses, and activated the mitochondrial apoptotic pathway. Nac treatment markedly improved cell viability, restored antioxidant capacity, reduced oxidative stress markers, and suppressed p53/Bax/Casp3-mediated apoptotic signaling. Combination analyses revealed an antagonistic interaction profile, indicating that Nac biologically limits Acr-induced cytotoxicity. Collectively, these findings demonstrate that Nac exerts protective effects in Leydig cells by modulating redox homeostasis and mitochondrial apoptosis, suggesting its potential as a protective regulator against Acr-induced reproductive toxicity.
Banu Orta Yilmaz, Iremnur Sarialioglu, Gokce Elmaci et al.· Drug and chemical toxicology...· 0 citations
