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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
Fri Feb 01 2019
Journal Name
Journal Of Pharmaceutical Sciences And Research
Protective Effects of Quercetin on Lipopolysaccharide -Induced Inflammation and Lipid Peroxidation in BALB/c Male Mice
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In the resent years, there is a robust scientific interest in discovery of new anti-septic and anti-oxidant naturally products with no/or limited side effects. The current study aimed to investigate the protective role of the quercetin on inflammations induced by lipopolysaccharide (LPS) in male mice A number of criteria included i.e. liver and spleen index and IL-6 and IL1-β cytokines level in spleen homogenate were considered. Sixty male mice (8-9 week age) was divided into six groups and treated for 5 days as the following: the first group represented control, the second and third group were injected with 5, 10 mg/kg b.w doses of quercetin respectively. While the fourth and fifth groups were co-treatment with (5, 10 mg/kg b.w.) intraper

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Publication Date
Sat Jan 01 2022
Journal Name
Journal Of Pharmaceutical Negative Results
Gentiopicroside ameliorates lipopolysaccharide-induced acute kidney injury by inhibiting TLR4/NF-κB signaling in mice model
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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
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
Tue Jun 11 2019
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Protective Effect of Ethanolic Extract of Mentha spicata Against Irinotecan-Induced Mucositis in mice
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Irinotecan induced-mucositis is an inflammatory event of intestine caused by an increase in concentration of active metabolite 7­ethyl­10-hydroxycamptothecin (SN­38) in the intestine. Irinotecan must first be converted by a carboxylesterase (CES) to the active metabolite (SN­38), which is subsequently glucuronidated by the hepatic enzyme to SN38G. The SN-38G is deconjugated in the intestine to SN-38 via ?-glucuronidase produced by the intestinal bacterial flora, which accounts for SN-38 delayed intestinal mucositis of irinotecan. To study the protective effect of mentha in irinotecan-induced mucositis, intestinal mucositis induced by I.P injection of irinotecan (75mg/Kg/day) for 4 days. Mentha ethanolic extract orally administered to

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Publication Date
Fri Mar 29 2024
Journal Name
Iraqi Journal Of Science
Involvement of Total Antioxidant Activity and eNOS Gene rs1799983/ rs2070744 Polymorphisms in Breast Carcinogenesis
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Globally, breast cancer is the common malignancy affecting women and understanding its associated molecular events could help in disease prevention and management strategies. The present study was set to investigate an association between total antioxidant capacity (TAC) and endothelial nitric oxide synthase (eNOS) polymorphisms with breast cancer. For this purpose, 100 subjects were participated in this work, including 50 female patients diagnosed with breast cancer recruited from Oncology hospital, Baghdad - Iraq and 50 healthy women as a control group. The concentration of antioxidants was measured in the serums collected from blood samples of breast cancer patients and healthy controls. While eNOS SNPs (rs1799983, G894T and rs2070744, T

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Publication Date
Tue Jun 23 2015
Journal Name
Nature Communications
A metabolic stress-inducible miR-34a-HNF4α pathway regulates lipid and lipoprotein metabolism
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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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Scopus (7)
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