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The occurrence of worsening pulmonary function has been connected to hypothyroidism (HPO). Hesperidin (HES) was suggested to have antioxidant, anti-proliferative, and anti-inflammatory potential. Our study’s objective was to determine whether HES could reduce carbimazole (CBZ)-induced lung injury more effectively than Eltroxin (ELT) in adult male albino rats or not. At random, 32 rats were distributed into four groups: Group I: normal control, to induce HPO, the remaining three groups were given CBZ (20 mg/kg/day) dissolved in distilled water for 1 week. They were then split up into three groups. Group II: orally administered CBZ (20 mg/kg b.w in water/day), Group III: HES (200 mg/kg/day) dissolved in 1% carboxymethyl-cellulose + CBZ treated, and Group IV: ELT (0.045 mg/kg/day) dissolved in distilled water + CBZ treated. All treatments were delivered for 12 weeks. Blood was collected to assess thyroid-stimulating hormone (TSH) and thyroid hormones (THs). Lung injury was evaluated based on the pulmonary content of interleukin (IL)-35, IL-6, and tumor necrosis factor-alpha (TNF-α), along with the estimation of lipid peroxidation, catalase, glutathione levels, superoxide dismutase, heme oxygenase-1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). The histological, ultrastructural, and immunohistochemical study of nuclear factor Kappa-B (NF-κB) and inducible nitric oxide synthase (iNOS), together with estimating the proliferation of cells using Antigen Ki-67 in lung tissue were performed. HES and ELT primarily suppressed variable lung damage mechanisms by suppressing TSH, the NF-κB/TNF-α pathway, iNOS, lipid peroxidation, Ki-67, and inflammatory mediators. On the other hand, they improved THs, antioxidant parameters, and the Nrf2/HO-1 pathway. HES and ELT exhibited an ameliorative effect that was reflected in the histopathological, immunohistochemical, and ultrastructural results. These results indicate that HES is a pneumoprotective agent that could be a promising treatment for oxidative stress, inflammation, and proliferation.

Background/Objectives: Despite the availability of antiepileptic drugs (AEDs) that can manage seizures, they often come with cognitive side effects. Furthermore, the role of oxidative stress and neuroinflammatory responses in epilepsy and the limitations of current AEDs necessitate exploring alternative therapeutic options. Medicinal plants, e.g., Lavandula dentata L., are rich in phenolic compounds and may provide neuroprotective and anti-inflammatory benefits. However, limited research evaluates their effectiveness in modulating neuroinflammation and histopathological changes in epilepsy models. Therefore, the current study hypothesized that treating Lavandula dentata L. extract or essential oils may reduce neuroinflammatory responses and mitigate histopathological changes in the brain, providing a natural alternative or adjunct therapy for epilepsy management. Methods: Five groups of male Wistar rats were used: control, pilocarpine-treated epileptic, valproic acid (VPA-treated epileptic), L. dentata extract, and essential oils. Numerous electrolyte levels, monoamine levels, neurotransmitter levels, and the mRNA expression of specific gate channel subtypes were evaluated in homogenate brain tissue. Additionally, histological changes in various brain regions were investigated. Results: The investigation revealed that the extract and essential oils obtained from L. dentata L. exhibited the ability to improve the modulation of electrolytes and ions across voltage- and ligand-gated ion channels. Furthermore, it was revealed that they could decrease neuronal excitability by facilitating repolarization. Moreover, L. dentata’s oil and ethanol extract re-balances T-reg/Th-17 cytokines, restoring the pro/anti-inflammatory cytokines and Treg markers, e.g., FOXP3 and CTLA-4, to their normal level. Conclusions: The present work confirms that the extract and essential oils of L. dentata L. have different activities to ameliorate the progression of histopathological alterations. Therefore, when used in conjunction with other AEDs, the extract and essential oils of L. dentata can slow the progression of epileptogenesis.

Nanoparticles have gained prominence in the formulation of nanopesticides, leveraging their unique nanocharacteristics. This study delves into the nephrotoxic implications of CuONanoSheet (CuONS), as nanopesticide tailored for agricultural applications to understand its safety and viability in this field. The nanocharacterization of CuONS was meticulously examined using X-ray diffraction, high-resolution transmission electron microscopy, field emission scanning electron microscopy and Zeta-Sizer device, which assessed zeta-potential, hydrodynamic size, and polydispersity index. Rats treated with CuONS showed elevated levels of blood urea nitrogen, creatinine, and uric acid and a significant increase in lipid peroxidation (MDA) and reduced levels of antioxidant enzymes. CuONS treatment resulted in an imbalance in pro-apoptotic Bax and anti-apoptotic B-cell lymphoma2 (Bcl2) levels. Histologically, CuONS induced glomerulus degeneration and vacuolation in tubules lining epithelium. Immunohistochemical evaluations revealed strong expressions of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), tumor necrosis factor-alfa (TNF-α), and the tumor suppressor gene (p53) in CuONS-treated kidneys. Ultrastructural assessments further confirmed these structural abnormalities. While CuONS exhibits potential as a nanopesticide, caution is warranted due to observed negative impacts on kidney functions, and histological architecture, in this study. Careful consideration of potential side effects on other living organisms is imperative in the utilization of CuONS in agricultural practices.

The aim of this study was to evaluate the anti-inflammatory, antioxidant, and antiproliferative effects of hesperidin (HSP) and eltroxin (ELT) on hypothyroidism (HPO) induced by carbimazole (CBZ) in white male albino rats. Thirty-two adult rats were categorized into four groups: Group 1, no treatment (control); Group II, treated with CBZ (20 mg/kg); Group III, treated with HSP (200 mg/kg) + CBZ; and Group IV, treated with ELT (0.045 mg/kg) + CBZ. All treatments were provided as oral daily doses for 90 days. Thyroid hypofunction was significantly manifested in Group II. However, increased levels of thyroid hormones, antioxidant enzymes, nuclear factor erythroid 2-related factor 2, heme oxygenase 1, and interleukin (IL)-10, and a decrease in the level of the thyroid-stimulating hormone were observed in Groups III and IV. On the contrary, decreased levels of lipid peroxidation, inducible nitric oxide synthase, tumor necrosis factor α, IL-17, and cyclooxygenase 2 were detected in groups III and IV. The histopathological and ultrastructural findings were ameliorated in Groups III and IV; on the contrary, Group II presented with significant increases in the height and number of layers of the follicular cells. Immunohistochemistry demonstrated a marked increase in thyroglobulin and significant decreases in the levels of nuclear factor kappa B and proliferating cell nuclear antigen in Groups III and IV. These results confirmed the effectiveness of HSP as an anti-inflammatory, antioxidant, and antiproliferative agent in rats with hypothyroidism. Additional studies are required to assess its potential as a novel agent against HPO. Graphical Abstract

Hypothyroidism (HPO) has been linked to a higher incidence of hepatic lesions. Hesperidin (HSP) is an antioxidant, anti-adipogenic, anti-inflammatory, anti-hyperlipidemic, and anti-apoptotic agent. Therefore, the study aimed to assess the impact of carbimazole (CBZ)-induced HPO on adult albino rats’ liver and explore the possible ameliorating effect of Eltroxin (ELT) and HSP. HPO was induced by CBZ (20 mg/kg/day). Rats were allocated into group I: normal control; group II: received CBZ (20 mg/kg/day) only; group III: received CBZ and HSP (200 mg/kg/day); and group IV: received CBZ and ELT (0.045 mg/kg/day). HSP and ELT attenuated dyslipidemia associated with HPO. HSP and ELT also significantly decreased elevated malondialdehyde and increased reduced glutathione levels and superoxide dismutase and catalase activities. Also, they markedly inhibited the expression of nuclear factor kappa B, inducible nitric oxide synthase, interleukin (IL)-1β, tumor necrosis factor-alpha, and alpha-smooth muscle actin. On the other hand, HSP successfully elevated nuclear factor erythroid 2-related factor 2, heme oxygenase 1, IL-37, proliferating cell nuclear antigen, and B-cell lymphoma 2 levels. Moreover, HSP decreased the activity of liver transaminases and increased total protein and albumin levels. HSP showed a protective effect on liver tissues of CBZ-treated rats. Our findings confirmed that HSP is an effective antioxidant that prevents and protects the liver from damage by CBZ. Therefore, HSP is a promising candidate for future use to minimize and alleviate HPO risks.

Copper oxide nanoparticles (CuONPs) have a wide range of uses in agricultural applications. Nanocurcumin (NCur) acts as an antioxidant treatment. The goal of the study is to reduce the toxicity resulting from the use of CuONPs as nanopesticides on living organisms by inducing changes in the morphological shape of CuONPs or treating it with NCur. So, we induced a comparative study between three shapes of CuONPs: CuO nanosphere (CuONSp), CuO nanosheet (CuONS), and CuO nanoflower (CuONF). We characterize each nano-form by using X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (HRTEM), and Zetasizer HT device; 36 rats were divided into six groups (n = 6): 1st group was the control group; 2nd group received 50 mg/kg/day of NCur orally for 30 days; 3rd, 4th, and 5th groups received orally 50 mg/kg/day of CuONSp, CuONS, and CuONF, respectively, for 30 days; 6th group received 50 mg/kg/day CuONSp plus 50 mg/kg/day of NCur orally for 30 days. An elevation occurred in malondialdehyde (MDA), liver and kidney functions, tumor necrosis factor-alpha (TNF-α), and B-cell lymphoma 2 (Bcl2) by CuONSp > CuONS > CuONF, respectively. An inhibition occurred in glutathione (GSH), superoxidase (SOD) catalase (CAT), apoptotic Bax gene (Bax), histopathological, and ultrastructural alterations by CuONSp < CuONS < CuONF, respectively. NCur ameliorated these alternations. In conclusion, CuONF is a better form compared to other forms of nanopesticide in agriculture due to its lower toxicity. NCur decreased the biological alternations which induced by CuONSp due to its antioxidant and anti-apoptotic properties.

Copper oxide nanoparticles (CuONPs) have a wide range of uses in agricultural applications. Nanocurcumin (NCur) acts as an antioxidant treatment. The goal of the study is to reduce the toxicity resulting from the use of CuONPs as nanopesticides on living organisms by inducing changes in the morphological shape of CuONPs or treating it with NCur. So, we induced a comparative study between three shapes of CuONPs: CuO nanosphere (CuONSp), CuO nanosheet (CuONS), and CuO nanoflower (CuONF). We characterize each nano-form by using X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (HRTEM), and Zetasizer HT device; 36 rats were divided into six groups ( n  = 6): 1st group was the control group; 2nd group received 50 mg/kg/day of NCur orally for 30 days; 3rd, 4th, and 5th groups received orally 50 mg/kg/day of CuONSp, CuONS, and CuONF, respectively, for 30 days; 6th group received 50 mg/kg/day CuONSp plus 50 mg/kg/day of NCur orally for 30 days. An elevation occurred in malondialdehyde (MDA), liver and kidney functions, tumor necrosis factor-alpha (TNF-α), and B-cell lymphoma 2 (Bcl2) by CuONSp > CuONS > CuONF, respectively. An inhibition occurred in glutathione (GSH), superoxidase (SOD) catalase (CAT), apoptotic Bax gene (Bax), histopathological, and ultrastructural alterations by CuONSp < CuONS < CuONF, respectively. NCur ameliorated these alternations. In conclusion, CuONF is a better form compared to other forms of nanopesticide in agriculture due to its lower toxicity. NCur decreased the biological alternations which induced by CuONSp due to its antioxidant and anti-apoptotic properties. Graphical Abstract

Copper oxide Nanoparticles (CuONPs) are used in different agricultural applications. Large amounts of CuONPs cause organ dysfunction in animals. Our study aim to compare between the toxic effects of CuONanSphere (CuONSp) and CuONanoFlower (CuONF) as new nano-pesticides, determine a less toxic form when used in agricultural applications. To characterize CuONSp and CuONF, we used X-ray diffraction (XRD), Field emission scanning electron microscopy (SEM), and High resolution transmission electron microscopy (HRTEM) and Zeta-sizer device.18 adult male albino rats were divided into three groups (n = 6), (I) control group, (II) and (III) groups were given orally 50 mg/kg/day of CuONSp and CuONF 30 days respectively. CuONSp induced oxidant-antioxidant abnormalities, including an increase in malondialdhyde (MDA) and a decrease in glutathione (GSH) in comparison to CuONF-treated one. CuONSp induced an increase in liver enzymes activities compared to CuONF. Tumour necrosis factor-alfa (TNF-α) detected an increased in liver and lung compared to CuONF. However, histological examinations revealed changes in CuONSp group than CuONF group. Changes in immune-expressions of TNF-α, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kβ) and tumour suppressor gene (p53) were also more identified in CuONSp group than CuONF group. Ultrastructural studies of liver and lung tissues marked alternations were observed in CuONSp group than CuONF group. In conclusion, CuONSp induced biological alternation in liver and lung more than CuONF. So, CuONF is less toxic compared to CuONSp when used as nano-pesticide in agricultural applications. Graphical abstract

: Despite the availability of antiepileptic drugs (AEDs) that can manage seizures, they often come with cognitive side effects. Furthermore, the role of oxidative stress and neuroinflammatory responses in epilepsy and the limitations of current AEDs necessitate exploring alternative therapeutic options. Medicinal plants, e.g., L., are rich in phenolic compounds and may provide neuroprotective and anti-inflammatory benefits. However, limited research evaluates their effectiveness in modulating neuroinflammation and histopathological changes in epilepsy models. Therefore, the current study hypothesized that treating L. extract or essential oils may reduce neuroinflammatory responses and mitigate histopathological changes in the brain, providing a natural alternative or adjunct therapy for epilepsy management. : Five groups of male Wistar rats were used: control, pilocarpine-treated epileptic, valproic acid (VPA-treated epileptic), extract, and essential oils. Numerous electrolyte levels, monoamine levels, neurotransmitter levels, and the mRNA expression of specific gate channel subtypes were evaluated in homogenate brain tissue. Additionally, histological changes in various brain regions were investigated. : The investigation revealed that the extract and essential oils obtained from L. exhibited the ability to improve the modulation of electrolytes and ions across voltage- and ligand-gated ion channels. Furthermore, it was revealed that they could decrease neuronal excitability by facilitating repolarization. Moreover, oil and ethanol extract re-balances T-reg/Th-17 cytokines, restoring the pro/anti-inflammatory cytokines and Treg markers, e.g., FOXP3 and CTLA-4, to their normal level. : The present work confirms that the extract and essential oils of L. have different activities to ameliorate the progression of histopathological alterations. Therefore, when used in conjunction with other AEDs, the extract and essential oils of can slow the progression of epileptogenesis.