Imidacloprid (IMI) is a widely used insecticide known for its high selectivity toward insects. Ellagic acid (EA) is a plant-derived polyphenolic compound recognized for its therapeutic potential and favorable safety profile in the treatment of various diseases. This study aimed to evaluate the therapeutic effects of EA, formulated as novasomes (NOV), against IMI-induced thyroid dysfunction and to investigate the underlying mechanisms. Rats were divided into four equal groups: control, EA-NOV, IMI, and IMI + EA-NOV. Thyroid function was assessed by measuring free triiodothyronine (T3), free thyroxine (T4), and thyroid-stimulating hormone (TSH) levels. Thyroid tissues were examined to evaluate histopathological alterations, as well as to assess the oxidative/antioxidant pathway (Nrf2, SOD, TAC, MDA), inflammatory pathway (IL-1β, TNF-α, NF-κB), apoptotic pathway (Bcl, BAX), and autophagy pathway (PI3K/Akt/mTOR, P53, Beclin-1). Exposure to IMI resulted in impaired thyroid function, the upregulated gene expression of the PI3K/Akt/mTOR pathway, and downregulated P53 expression. Additionally, immunohistochemical staining revealed Beclin-1-mediated autophagy, alongside increased apoptosis, oxidative stress, and elevated levels of inflammatory cytokines. Conversely, EA improved thyroid function and ameliorated histopathological alterations by enhancing autophagy-inducing pathways. Additionally, the alleviation of oxidative stress was evidenced by the increased immunohistochemical staining of Nrf2, which promoted the synthesis and activity of antioxidant enzymes and reduced apoptotic and inflammatory markers. This study proposes the use of EA as a potential protective, naturally occurring phytoceutical against IMI-induced thyroid dysfunction, primarily through the modulation of PI3K/Akt/mTOR-mediated autophagy.

Bisphenol A (BPA) is among the most industrial compounds worldwide. BPA belongs to a group of compounds that are categorized as endocrine disruptive chemicals resulting in multi organ toxicities. Garlic, a natural plant, has a recorded history in ancient medicine. Royal Honey possesses antioxidant and anti-inflammatory properties against many contaminants. Aim: to compare effect of aged garlic extract (AGE) and royal honey (RH) on protection against gastric mucosal damage by Bisphenol A consumption.For the study, four equal groups of forty rats were established. The control group had ten rats. For 28 days, the remaining thirty rats were given an oral dosage of 50 mg/kg of bisphenol A; ten rats of whom were assigned to group II. Other ten rats (group III) were pretreated with AGE (200 mg/kg) daily orally one hour before Bisphenol A. whereas the remaining ten rats (group IV) were pretreated with RH (250 mg/kg) daily orally one hour before Bisphenol A. The stomach was investigated using Haematoxylin and Eosin, a scanning electron microscope, Periodic Acid Schiff stain, caspase 3 and TNF- α immunostaining.Bisphenol A treated group showed cell degeneration and erosions on the epithelial surface. The cytoplasmic reactivity of TNF- α and caspase 3 immunostaining is elevated, indicating a malfunction in the gastric mucosa. The pretreatment of AGE and RH mitigates the histopathological alterations with a significant decrease in TNF- α and caspase 3 immunreactivity.This study highlights the protective effects of natural compounds against BPA-induced gastric mucosal damage by reducing inflammation and apoptosis markers.

Background: The hippocampus, a key region for learning and memory, is highly susceptible to excitotoxicity from excessive glutamate receptor activation, leading to neuronal injury or death. Monosodium glutamate (MSG), a common food additive, has been associated with various neurotoxic and neurodegenerative effects.Materials and Methods: Adult rats were used to evaluate the protective effects of vitamin C and melatonin against MSG-induced hippocampal damage. Sixty rats were divided into five groups: control, MSG (2 g/kg), VC (MSG + 100 mg/kg vitamin C), ML (MSG + 10 mg/kg melatonin), and ML+VC (MSG + both vitamin C and melatonin). Treatments were administered orally for 28 days. Hippocampal tissues were collected for histological and immunohistochemical analysis of GFAP, TNF-α, and caspase-3 expression. Ethical approval was obtained from the Institutional Animal Care and Use Committee (IACUC) of Benha University, Egypt.Results: MSG exposure significantly increased GFAP, TNF-α, and caspase-3 expression, indicating neuroinflammation, apoptosis, and marked histological alterations in the CA1 region. In the VC group, some pyramidal neurons were distorted with scattered glial cells and vacuolations, whereas in the ML group, pyramidal neurons were more densely packed with minimal glial pyknosis and vacuolations. Combined melatonin and vitamin C treatment largely preserved hippocampal architecture and markedly reduced inflammatory and apoptotic markers.Conclusion: MSG exerts pronounced neurotoxic effects in the rat hippocampus. Co-administration of vitamin C and melatonin produced a synergistic neuroprotective effect, highlighting their potential to mitigate MSG-induced hippocampal damage.

Chlorfenapyr (CFP) is a widely used pesticide associated with nephrotoxicity through oxidative stress, inflammation, and mitochondrial dysfunction. This study investigated the protective effects of limonene (LM) and its nano-liposomal formulation (LM-LNPs) against CFP-induced renal injury in rats. Animals were divided into six groups—control, LM, LM-LNPs, CFP, CFP + LM, and CFP + LM-LNPs—and treated orally for 30 days. CFP exposure resulted in marked renal dysfunction, histopathological and ultrastructural damage, suppression of the NRF2/HO-1/NQO1 antioxidant pathway, depletion of endogenous antioxidants excessive generation of reactive oxygen and nitrogen species, lipid peroxidation products, and DNA damage. These changes were accompanied by activation of NF-κB/COX-2-mediated inflammation, mitochondrial respiratory impairment, disrupted energy metabolism, and induction of apoptosis. Co-treatment with LM significantly ameliorated these alterations, whereas LM-LNPs produced greater improvements in renal function, tissue architecture, redox homeostasis, mitochondrial function, and inflammatory and apoptotic signaling. Immunohistochemical analyses further confirmed enhanced NRF2 expression and reduced NF-κB immunoreactivity in LM-LNP-treated kidneys. Overall, nano-liposomal delivery enhanced the renoprotective efficacy of limonene, highlighting its potential as a therapeutic strategy against pesticide-induced kidney injury.

Background: Hyperglycemia is a chronic illness that is associated with diabetes. Patients with diabetes have been found to have many alterations in their renal functioning. The aim of this study was to evaluate the potential benefits of diosmin and ginger, either separately or in combination, for diabetic nephropathy that was experimentally produced.Materials and Methods: Group I, ten rats stood as a control group. All rats (except control group) were given a single intraperitoneal dose of alloxan (150 mg/kg body weight) to induce type 2 diabetes. Group II consisted of ten diabetic rats. Other ten diabetic rats received 100 mg/kg diosmin orally for six weeks as part of Group III. Also other ten diabetic rats; part of Group IV received 400 mg/kg of ginger orally for six weeks. The last ten diabetic rats in Group V received oral treatment for six weeks with ginger (400 mg/kg) and diosmin (100 mg/kg). Rats were sacrificed after the six weeks, and kidney tissue and blood samples were taken for several biochemical analyses. Both an ultrastructural investigation and hemotoxylin and eosin staining were performed. The desmin and Nrf2 immunohistochemical markers were used. There were statistical and morphometric studies performed. Results: the diosmin plus ginger therapy showed a considerable decrease in blood glucose, urea, and creatinine in contrast to rats with diabetes. After six weeks, there was a noticeable recovery in the levels of malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD). Histopathological analysis verified that group V likewise had apparently normal renal tissue architecture. When compared to the diabetic group, area% of Desmin in group V was much lower, while its area% of Nrf2 was significantly greater. Conclusion: Ginger treatment alone or in combination with diosmin exhibited more pronounced improvement in diabetic nephropathy.

Background: Acute pancreatitis (AP) remains a potentially fatal disease with limited effective therapies. Mesenchymal stem cells (MSCs) exhibit antioxidant and immunomodulatory properties, while Rosmarinic acid (RA) has anti-inflammatory and cytoprotective effects. Objective: This study aimed to evaluated their therapeutic potential in experimental AP. Methods: Forty-one male Sprague-Dawley rats were randomly assigned into four groups: Control (I), L-arginine–induced AP (II), L-arginine + RA (50 mg/kg, i.p., once) (III), and L-arginine + MSCs (1×10⁶ cells/ml, i.v.) (IV). Assessments included serum amylase, TNF-α, and IL-10 levels, histopathology, and immunohistochemistry for proliferating cell nuclear antigen (PCNA) and inducible nitric oxide synthase (iNOS). Results: Both RA and MSCs significantly reduced serum amylase and TNF-α and increased IL-10 compared to AP rats. MSCs produced the greatest improvements, though differences between groups III and IV were not statistically significant. Histologically, RA preserved acinar architecture with moderate protection, while MSCs restored near-normal pancreatic structure, reduced apoptosis and necrosis, enhanced PCNA expression, and markedly decreased iNOS reactivity. Conclusions: RA and MSCs both demonstrated therapeutic benefits in arginine-induced AP, with MSCs showing superior efficacy in biochemical, histological, and immunohistochemical outcomes. MSCs appear more effective than RA in attenuating inflammation and promoting pancreatic repair, warranting further investigation into their mechanisms and potential clinical application.