Hala Attia

Background/Objectives: Amiodarone (AmoD) is an effective antiarrhythmic drug whose use is limited by life-threatening pulmonary fibrosis. Although Wnt/β-catenin signaling contributes to several lung diseases, its involvement in AmoD-induced pulmonary fibrosis remains unknown. This study investigated whether Wnt/β-catenin signaling is altered during AmoD-induced pulmonary fibrosis and whether its pharmacological modulation with pyrvinium (Pyrv) attenuates this toxicity. Methods: Rats were allocated into four groups and treated for five weeks as follows: normal control, AmoD (30 mg/kg/day), Pyrv (60 µg/kg/day), and AmoD + Pyrv. Pulmonary injury and fibrosis were evaluated using histopathological examination, Masson’s trichrome staining, immunohistochemical assessment of collagen I, α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1), and measurement of inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and Th1/Th2-related cytokines. Wnt/β-catenin-associated proteins, including Wnt3a, active β-catenin, and glycogen synthase kinase-3β (GSK-3β), were evaluated by Western blotting. Results: AmoD induced marked pulmonary architectural disruption, inflammatory cell infiltration, increased lung weight/body weight ratio, collagen deposition, and increased expression of TGF-β1, α-SMA, and collagen I, as well as increased levels of TNF-α, IL-6, and disruption of Th1/Th2 immune balance. At the molecular level, AmoD increased Wnt3a, active β-catenin, and the p-GSK-3β/total GSK-3β ratio. Co-administration of Pyrv significantly attenuated the histopathological, inflammatory, immune, and fibrotic alterations and reduced the AmoD-associated changes in Wnt/β-catenin-related proteins. Conclusions: The findings indicate that AmoD-induced pulmonary injury and fibrosis are associated with modulation of Wnt/β-catenin related proteins and that Pyrv treatment attenuates these pathological changes. Targeting this pathway could be a promising protective strategy to prevent fibrogenesis during AmoD treatment.

Renal ischemia/reperfusion injury (RI/RI) is one of the major causes of acute kidney injury (AKI). Low molecular weight-dextran sulphate (LMW-DS) is a bioactive polysaccharide with anti-inflammatory and cytoprotective properties. This study investigated the nephroprotective potential of LMW-DS against the RI/RI. RI/RI rat model underwent surgery that involved a complete bilateral clamping of renal hila for 30 min, followed by unclamping for 30 min. LMW-DS (5 mg/kg, s.c.) was injected 5 min before unclamping. After 24 h, kidneys were collected for biochemical, histopathological, and immunohistochemical examinations. RI/RI dramatically induced renal deterioration, as reflected by marked elevation in the levels of renal oxidative stress, tumor necrosis factor-α, interleukin-6, and toll-like receptor-4, indicating lipid peroxidation and inflammatory response. Furthermore, RI/RI caused upregulation of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Additionally, morphological alterations and collagen deposition were also detected in kidney tissues. The immunohistochemical analysis revealed a strong positive immunoreaction for p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and caspase-3. Treatment with LMW-DS produced a pronounced amelioration in the altered parameters induced by RI/RI. In conclusion, LMW-DS exerts nephroprotective effects against RI/RI by restoring redox balance, suppressing inflammatory signaling, JNK/p38 MAPK, and caspase-3, highlighting its potential as a therapeutic strategy for renal I/R-induced AKI.

Diclofenac sodium (DCFN) is the most often prescribed NSAID, however its prolonged administration is linked to cardiotoxicity mediated by oxidative stress, inflammation, and apoptosis. The role of the Wnt/β-catenin pathway in cardiac injury is well documented; however, it remains unclear whether this pathway is upregulated in the heart during DCFN treatment. This work aims to investigate the cardiac activity of this pathway in DCFN-intoxicated rats and to explore the potential cardioprotective effects of montelukast (MNTL), a leukotriene receptor antagonist. Four groups of male rats were treated as follows for 14 days: control, MNTL control (20 mg/kg, p.o), DCFN (10 mg/kg, i.m), and DCFN+MNTL. Cardiac injury was assessed by serum biomarkers (cardiac troponin-I, creatine kinase-MB, lactate dehydrogenase, and aspartate aminotransferase), oxidative stress markers (malondialdehyde, glutathione, superoxide dismutase), pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6), as well as apoptotic proteins (Bcl-2 and caspase-3). Protein expression of Wnt-1, active β-catenin, and Frizzled-1 (FZD1) was evaluated, and histological analysis of cardiac tissues was performed. DCFN treatment resulted in significant cardiac injury, characterized by elevated serum cardiac biomarkers, increased oxidative stress and inflammatory cytokines, upregulated apoptotic markers, and overexpression of Wnt-1/active β-catenin and FZD-1. Histological examination revealed myocardial degeneration, vascular compression, and marked inflammatory cell infiltration. Co-treatment with MNTL significantly mitigated these biochemical, molecular, and histopathological alterations. In conclusion, the Wnt/β-catenin pathway is activated in the heart during DCFN treatment, suggesting its possible role in its cardiotoxicity. MNTL effectively attenuates this toxicity, highlighting its potential as a cardioprotective agent during NSAID therapy.

Background/Objectives: Medicinal plants such as Santolina chamaecyparissus L., an evergreen shrub from the Asteraceae family, have long been valued for their bioactive compounds and traditional therapeutic uses. Materials: In this study, the essential oil of S. chamaecyparissus (EOSC) was isolated via hydrodistillation and then comprehensively evaluated for its phytochemical composition and antioxidant, anti-inflammatory, hemolytic, and cytotoxic properties, as well as its in silico bioactivity. Results: In total, 89.5% of the essential oil composition was successfully identified using GC-MS analysis. Hydrocarbon sesquiterpenes constituted the largest fraction (36.0%), followed by oxygenated sesquiterpenes (19.7%). Phytochemical screening revealed high phenolic content (839.50 ± 5.0 mg GAE/g E.O), while the Total Antioxidant Capacity (TAC) assay confirmed its strong antioxidant potential. The oil showed moderate hemolytic activity and significant lipoxygenase inhibition, indicating anti-inflammatory capability. The cytotoxic effects of the EOSC were evaluated using the MTT assay and HepG2 liver cancer cells. A dose-dependent reduction in cell viability was observed, confirming the oil’s strong anticancer activity. Molecular docking and ADMET analyses supported the bioactivity of the identified compounds, which showed good drug-likeness and pharmacokinetic properties. Conclusions: These findings demonstrate that EOSC has promising antioxidant and anti-inflammatory properties, suggesting that it could have potential as a safe natural substance for use in drug development and food preservation.

Depression is a psychiatric disorder that affects people globally, harming overall health. This study assessed the antidepressant effects of ruta oil (RO), obtained from Ruta chalepensis, using a depression model induced by social isolation (SI) for 30 days. Rats were divided into the following groups: normal control (4 rats per cage), RO control (400 mg/kg, 4 rats per cage), SI model (one rat per cage), SI+RO (200 mg/kg), SI+RO (400 mg/kg) and SI+fluoxetine (standard anti-depressant drug, 200 mg/kg). Behavioural alterations in rats were examined using the forced swim test (FST), open field test (OFT), and the sucrose preference test. Levels of lipid peroxidation, dopamine (DOP) and serotonin (SER), as well as the brain-derived neurotrophic factor (BDNF) levels in the hippocampus were quantified using enzyme-linked immunosorbent assay. Histological examination was performed using hematoxylin and eosin. SI results in the following behavior changes; suppressed locomotor activity (reflected by a decreased number of crossings in the OFT and an increase in immobility time in the FST), reduced exploratory behavior (indicated by a decreased frequency of rearing in OFT) and anhedonia (indicated by decreased sucrose preference). The hippocampal levels of DOP, SER, and BDNF levels were attenuated, while lipid peroxidation was elevated in socially isolated rats. In addition, histological examination revealed shrunken and dead pyramidal neurons and degenerated granular neurons in the granule cell layer of the hippocampus. Treatment with RO at both doses significantly attenuated the behavioural changes, biochemical alterations and neuronal damage induced by SI. In conclusion, RO effectively alleviated depression by enhancing the levels of neurotransmitters and BDNF, while reducing lipid peroxidation in the hippocampal tissues of rats. This study confirms that RO can serve as a reliable source of safe, plant-derived treatment and a powerful remedy for neurological disorders, either on its own or in combination with other medications.

Background/Objectives: This study aimed to analyze the chemical composition and biological activities of Artemisia absinthium L. essential oil, focusing on its antioxidant and enzyme inhibition (α-amylase and urease) properties. Additionally, in vitro pharmacokinetic and pharmacodynamic evaluations were conducted through in silico molecular docking and BOILED-Egg models to assess its therapeutic potential and its potency in treating oxidative-stress-related diseases. Methods: The essential oil was isolated by the hydrodistillation (HD) of fresh plant material, and volatiles released from dried plant material were sampled via headspace solid-phase microextraction (HS-SPME), followed by a phytochemical profiling analysis through the GC-MS tool. Antioxidant capacity was assessed using DPPH, ABTS, FRAP, and nitric oxide scavenging assays, while enzyme inhibition activities were tested against α-amylase and urease. Molecular docking and BOILED-Egg models were used to evaluate compound interactions with NADPH oxidase and predict pharmacokinetic behavior, respectively. Results: HS-SPME and HD yielded 46 and 25 compounds, respectively, primarily terpenoids represented by camphor (26.4%) and cis-davanone (18.0%) in HS-SPME, while in the HD essential oil, cis-davanone (60.2%) and chamazulene (10.8%) were most prevalent. The antioxidant assays showed a strong activity, with a total antioxidant capacity of 821.8 mg ascorbic acid Eq/gm. The essential oil inhibited urease by 86.7% and α-amylase by 81.8%. Molecular docking showed strong binding affinities with NADPH oxidase, supporting the antioxidant results. Conclusions:A. absinthium EO demonstrated potent antioxidant and enzyme inhibitory activities, suggesting its therapeutic potential for treating enzyme-related disorders like diabetes mellitus and its possible use as a cure for many oxidative-stress-related diseases, thus validating the folkloric use of this plant.

Diclofenac sodium (DIC) is a widely used non-steroidal anti-inflammatory drug. Unfortunately, its prolonged use is associated with nephrotoxicity due to oxidative stress, inflammation, and fibrosis. We aimed to investigate the nephroprotective effects of vitamin B complex (B1, B6, B12) against DIC-induced nephrotoxicity and its impact on NOX4/RhoA/ROCK, a pathway that plays a vital role in renal pathophysiology. Thirty-two Wistar rats were divided into four groups: (1) normal control; (2) vitamin B complex (16 mg/kg B1, 16 mg/kg B6, 0.16 mg/kg B12, intraperitoneal); (3) DIC (10 mg/kg, intramuscular); and (4) DIC plus vitamin B complex group. After 14 days, the following were assayed: serum renal biomarkers (creatinine, blood urea nitrogen, kidney injury molecule-1), oxidative stress, inflammatory (tumor necrosis factor-alpha, interleukin-6), and fibrotic (transforming growth factor-beta) markers as well as the protein levels of NOX4, RhoA, and ROCK. Structural changes, inflammatory cell infiltration, and fibrosis were detected using hematoxylin and eosin and Masson trichrome stains. Compared to DIC, vitamin B complex significantly decreased the renal function biomarkers, markers of oxidative stress and inflammation, and fibrotic cytokines. Glomerular and tubular damage, inflammatory infiltration, and excessive collagen accumulation were also reduced. Protein levels of NOX4, RhoA, and ROCK were significantly elevated by DIC, and this elevation was ameliorated by vitamin B complex. In conclusion, vitamin B complex administration could be a renoprotective approach during treatment with DIC via, at least in part, suppressing the NOX4/RhoA/ROCK pathway.

Tamoxifen (TAM) is a commonly used drug for breast cancer treatment. Although effective, TAM has deleterious effects on many organs. The toxic effects of TAM on the pancreas and the underlying mechanisms however, have not fully investigated. In the present study, we investigated the effects of TAM on the pancreatic tissue in female rats. We also examined whether cardamom aqueous extract (CAE) protects against TAM-induced pancreatic injury. TAM-intoxicated rats were injected with 45 mg/kg of TAM for 10 days, whereas rats in the CAE-treated group were administered 10 mL/kg of CAE for 20 days, starting 10 days prior to TAM administration. Treatment with TAM resulted in severe degeneration of the pancreatic acini and marked increases in the serum levels of pancreatic lipase, α-amylase, glucose, fatty acids and triglycerides along with decreased insulin serum levels. TAM led to oxidative stress as evident from a significant increase in the pancreatic levels of lipid peroxides and nitric oxide along with the depletion of reduced glutathione, glutathione peroxidase, and superoxide dismutase. Moreover, inflammation was indicated by a significant increase in tumor necrosis factor–α and interleukin-6 levels, enhanced expression of the macrophage recruitment marker; CD68 as well as up-regulated protein levels of toll-like receptor 4 and nuclear factor kappa B and increased p-p38/MAPK ratio; which are important signals in the production of inflammatory cytokines. TAM also markedly increased the pancreatic levels of caspase-3 and BAX reflecting its apoptotic effects. The CAE treatment ameliorated all the biochemical and histological changes induced by TAM. The present study revealed, for the first time, that TAM has toxic effects on the pancreatic tissue through oxidative stress, inflammation and apoptotic effects. The present study also provides evidence that CAE exerts cytoprotective effects against these deleterious effects induced by TAM in the pancreatic tissue.