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Comparative Hepatoprotective Effects of Dapagliflozin and Silymarin Against Cyclophosphamide-Induced Liver Injury in Rats: Involvement of Nrf2/HO-1, HNF4α, and HNF6 Pathways
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Background: Cyclophosphamide (Cpd), a common immunosuppressive and chemotherapeutic drug, can cause hepatotoxicity by inducing inflammation and oxidative stress. Dapagliflozin (Dapa) and other sodium-glucose cotransporter-2 inhibitors (SGLT2i) have anti-inflammatory and antioxidant properties, and Silymarin is a natural compound extracted from the seeds of the milk thistle plant (Silybum marianum). It is best known for its antioxidant, anti-inflammatory, and hepatoprotective effects.Objective: By measuring oxidative stress, inflammation, and liver regeneration parameters, with an emphasis on the Nrf2/HO-1 pathway and hepatocyte nuclear factors (HNF4α and HNF6), Dapa's hepatoprotective effects in comparison to Sil on Cpd-induced liver injury will be evaluated. Methods: Five (5) groups of male rats ten rats each were created: control, vehicle (Na-CMC), Cpd (30mg/kg), Cpd + Dapa (3mg/kg), and Cpd + Sil (200mg/kg).. Rat liver tissue was examined for Nrf2, HO-1 (qRT-PCR), HNF4α (ELISA), and HNF6 (Western blot) levels after ten days. Results: Cpd significantly reduced Nrf2, HO-1, HNF4α, and HNF6 levels (*p < 0.0001). Dapa and Sil restored these markers, with Dapa showing superior upregulation of Nrf2 (2.182 ± 0.540 vs. Cpd 0.244 ± 0.096) and HO-1 (2.051 ± 0.533 vs. CP 0.487 ± 0.178) (*p< 0.0001). Dapa also significantly increased HNF4α (2135 ± 297.9 vs. CP 229.5 ± 50.21) and HNF6 (3.635 ± 0.610 vs. CP 0.515 ± 0.255) (*p< 0.001), outperforming Sil in enhancing HNF6 (*p < 0.05). Conclusion: Dapa ameliorates Cpd-induced hepatotoxicity by activating the Nrf2/HO-1 pathway and restoring HNF4α/HNF6 expression, demonstrating comparable or superior efficacy to Sil. These findings highlight Dapa’s potential as an adjunct therapy to mitigate chemotherapy-induced hepatotoxicity

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Publication Date
Thu Sep 01 2022
Journal Name
Archives Of Razi Institute
Effects of Avena sativa and Glycyrrhiza glabra Leaves Extracts on Immune Responses in Serum Cytokine and Liver Enzyme Levels in NIH Mice
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In addition to their high quantities of active chemicals, medicinal plants are well-known for their pharmacological qualities, which include immunological modulation. T Consequently, this study aimed to examine the effects of Avena sativa and Glycyrrhiza glabra leaf extracts on immunological responses as measured by blood cytokine and liver enzyme levels. The phytochemical analysis of Avena sativa crude leaf extracts revealed the presence of alkaloids,flavonoids, tannins, phenolic compounds, and saponins but the absence of resins and violet oils. On the other hand, violet oils, flavonoids, tannins, saponins, and glycosides were detected in significant concentration in Glycyrrhiza glabra ethanolic extract, although resins and phenolic compou

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Publication Date
Mon Dec 01 2025
Journal Name
Toxicology Reports
Butein mitigates 5-FU-triggered hepatotoxicity via antioxidant, anti-inflammatory, and anti-apoptotic pathways
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5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent, but its hepatotoxic potential poses clinical challenges, as it induces oxidative stress, inflammation, and apoptosis in liver tissue. Butein, a natural chalcone flavonoid that possesses varied biological activity, such as anticancer, anti-inflammatory, and antiplatelet effects. This study aimed to evaluate the possible protective effects of Butein against 5-FU-induced hepatotoxicity in rats. Male albino rats were divided into 4 Groups (of 7 animals each): control, 5-FU, and two Butein-pretreated Groups (50 and 100 mg/kg/day, orally for 14 days) each before a single intraperitoneal dose of 150 mg/kg 5-FU, which was injected on day 14. Serum liver enzymes (ALT and AST), cytokines

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Publication Date
Sat Jan 01 2022
Journal Name
Journal Of Advanced Pharmacy Education And Research
Estimation of the healing effects of the topical use of MEBO and hyaluronic acid gel in the burned rats
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Exposing the dorsal superficial skin of rats to partial-depth burn leads to bacterial and microbes Invasion. Topical treatment is required in most superficial burn cases Moist exposed burn ointment (MEBO) protects wounds from infection and enhances healing without any harmful effects of purified chemicals is caused. The topical using of HA gel in rat models with full and partial thickness surgical wounds shows enhancement in wound repair. In this study, we compared the healing efficacy of topical use of hyaluronic acid gel products with MEBO as standard management in rats that were exposed to a partial-thickness burn. The experiment included twenty-four (24) adult albino rats of male sex with weight (150-220 gm) of 3 months’ age divided i

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Publication Date
Thu Aug 31 2023
Journal Name
Materials
Comparative Analysis of Reinforced Asphalt Concrete Overlays: Effects of Thickness and Temperature
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Reflection cracking in asphalt concrete (AC) overlays is a common form of pavement deterioration that occurs when underlying cracks and joints in the pavement structure propagate through an overlay due to thermal and traffic-induced movement, ultimately degrading the pavement’s lifespan and performance. This study aims to determine how alterations in overlay thickness and temperature conditions, the incorporation of chopped fibers, and the use of geotextiles influence the overlay’s capacity to postpone the occurrence of reflection cracking. To achieve the above objective, a total of 36 prism specimens were prepared and tested using an overlay testing machine (OTM). The variables considered in this study were the thickness of the

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Publication Date
Thu Aug 31 2023
Journal Name
Materials
Comparative Analysis of Reinforced Asphalt Concrete Overlays: Effects of Thickness and Temperature
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Reflection cracking in asphalt concrete (AC) overlays is a common form of pavement deterioration that occurs when underlying cracks and joints in the pavement structure propagate through an overlay due to thermal and traffic-induced movement, ultimately degrading the pavement’s lifespan and performance. This study aims to determine how alterations in overlay thickness and temperature conditions, the incorporation of chopped fibers, and the use of geotextiles influence the overlay’s capacity to postpone the occurrence of reflection cracking. To achieve the above objective, a total of 36 prism specimens were prepared and tested using an overlay testing machine (OTM). The variables considered in this study were the thickness of the

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Publication Date
Mon Oct 07 2024
Journal Name
F1000research
Oral pre-treatment with Citronellol ameliorates Methotrexate-induced nephrotoxicity in Wistar rats via targeting oxidative stress and inflammation
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Background Methotrexate (MTX) is a classical folic acid antagonist widely used in the treatment of malignant and non-malignant disorders. However, its clinical application is often restricted by concomitant adverse effects, including renal damage. Numerous studies have highlighted the role of oxidative stress and inflammation in mediating MTX-related nephrotoxicity. Therefore, the current study aimed to explore the possible renoprotective action of Citronellol (CT), a natural compound with prominent antioxidant and anti-inflammatory activities, against nephrotoxicity induced by MTX. Methods To fulfill our objective, 24 adult male Wistar rats were randomly allocated into four groups: control, MTX, 100 mg/kg CT plus MTX and 200 mg/kg C

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Publication Date
Mon Oct 07 2024
Journal Name
F1000research
Oral pre-treatment with Citronellol ameliorates Methotrexate-induced nephrotoxicity in Wistar rats via targeting oxidative stress and inflammation
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Background Methotrexate (MTX) is a classical folic acid antagonist widely used in the treatment of malignant and non-malignant disorders. However, its clinical application is often restricted by concomitant adverse effects, including renal damage. Numerous studies have highlighted the role of oxidative stress and inflammation in mediating MTX-related nephrotoxicity. Therefore, the current study aimed to explore the possible renoprotective action of Citronellol (CT), a natural compound with prominent antioxidant and anti-inflammatory activities, against nephrotoxicity induced by MTX. Methods To fulfill our objective, 24 adult male Wistar rats were randomly allocated into four groups: control, MTX, 100 mg/kg CT plus MTX and 200 mg/kg C

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Publication Date
Wed Jul 01 2020
Journal Name
Biochemical And Cellular Archives
Histopathological changes in liver induced by piroxicam administration in adult male albino mice mus musculus
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Publication Date
Thu Aug 24 2023
Journal Name
Nativa
CONCENTRATIONS OF SILYMARIN ON THE RUMEN ACTIVITIES IN LAMBS
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Silymarin is derived from the milk thistle plant, and possesses numerous pharmacological actions, including hepatoprotective, anti-inflammatory, antioxidant, and anticancer properties. The aim of the study was to the determination of influence different concentrations of Silymarin on the rumen performance in 30 local lambs (divided into three groups of 10 lambs each). In the first and second groups, 420 and 210 mg kg-1 of silymarin were administered for 8 weeks, and the third group was the control, which received normal saline solution. The parameters evaluated included the level of volatile fatty acids (VFAs), ammonia and pH in the rumen. Furthermore, the in vitro digestibility of ash, protein, fat and dry matter was investigated.

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Publication Date
Thu Oct 01 2026
Journal Name
Journal Of Baghdad College Of Dentistry
The effects of bisphosphonate administration on teeth development and growth of the jaw bones in neonatal rats (histological and immunohistochemical study)
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Background: Bisphosphonates are potent inhibitors of osteoclastic bone resorption and widely used for the treatment of osteoporosis, and osteogenesis imperfecta in children. Clinical and experimental studies have demonstrated that Bisphosphonates delay or inhibit tooth eruption. This study tries to focus on the effect of bisphosphonate on teeth development and jaw bones growth. Materials and methods: The present study includes 65 neonatal rats during lactation period from 15 Albino Wister rats mother. Alendronate (one type of Bisphosphonates) was administrated orally (15 mg/kg) into 10 pregnant rats two times a week, while other 5 rats regard as control. Then the neonatal rats sacrificed in I, 6, 11, 16 and 21 days. The lower first molar we

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