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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 Oct 11 2024
Journal Name
F1000research
Unleashing the cardioprotective potential of Ezetimibe against Doxorubicin-induced cardiotoxicity in Wistar rats: Targeting oxidative stress and NF-κB-mediated inflammation
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Background Doxorubicin (DOX) is a potent antineoplastic agent used in treating various adult and pediatric cancers, but it tends to provoke dose-dependent cardiotoxicity. Ezetimibe (EZE), a cholesterol-lowering drug, has been reported to possess defensive actions against oxidative stress and inflammation, which are two of the main proposed mechanisms underlying the development of DOX-induced cardiotoxicity (DIC), hence, we aimed to inspect the possible protective effect of EZE against DIC in rats. Methods 24 adult male Wistar rats were allocated into four groups of six: control, DOX, 10 mg/kg EZE plus DOX and 20 mg/kg EZE plus DOX. At the end of the study, the experimental rats were anesthetized and blood samples were collected for b

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Publication Date
Wed Mar 07 2018
Journal Name
Journal Of Cellular And Molecular Medicine
Resveratrol protects mice against SEB‐induced acute lung injury and mortality by miR‐193a modulation that targets TGF‐β signalling
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Abstract<p>Staphylococcal enterotoxin B (SEB) is a potent superantigen produced by <italic>Staphylococcus aureus</italic> that triggers a strong immune response, characterized by cytokine storm, multi‐organ failure, and often death. When inhaled, SEB can cause acute lung injury (ALI) and respiratory failure. In this study, we investigated the effect of resveratrol (RES), a phytoallexin, on SEB‐driven ALI and mortality in mice. We used a dual‐exposure model of SEB in C3H/HeJ mice, which caused 100% mortality within the first 5 days of exposure, and treatment with RES resulted in 100% survival of these mice up to 10 days post‐SEB exposure. RES reduced the inflammatory cytokines in the serum an</p> ... Show More
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Publication Date
Mon Nov 14 2022
Journal Name
Asian Journal Of Water, Environment And Pollution
Effect of Sodium Fluoride on Glycemic Index and Liver Functions in Rats
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From a health standpoint, fluoride (F) is a vital element for humans. It had harmful effects on numerous organs when consumed in high dosages. Fluoride poisoning has been linked to liver damage. The purpose of this study was to see how sodium fluoride (Naf) affected liver function and the glycemic index in adult male albino rats. Fourteen (14) adult male Wistar albino rats were randomly and evenly divided into two groups and given the following treatments for thirty (30) days: G1 Group (Control group), were given distilled water and fed a balanced diet, G2 rats were administered water that contained 100 ppm Naf. The animals were fasted for 8-12 hours before being anesthetized and blood samples were taken by heart puncture technique

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Publication Date
Mon Nov 14 2022
Journal Name
Asian Journal Of Water, Environment And Pollution
Effect of Sodium Fluoride on Glycemic Index and Liver Functions in Rats
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From a health standpoint, fluoride (F) is a vital element for humans. It had harmful effects on numerous organs when consumed in high dosages. Fluoride poisoning has been linked to liver damage. The purpose of this study was to see how sodium fluoride (Naf) affected liver function and the glycemic index in adult male albino rats. Fourteen (14) adult male Wistar albino rats were randomly and evenly divided into two groups and given the following treatments for thirty (30) days: G1 Group (Control group), were given distilled water and fed a balanced diet, G2 rats were administered water that contained 100 ppm Naf. The animals were fasted for 8-12 hours before being anesthetized and blood samples were taken by heart puncture technique

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Publication Date
Sat Jun 18 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Anti-Inflammatory Activity of Gingko Biloba Extract in Cotton Pellet-Induced Granuloma in Rats: A comparative Study with Prednisolone and Dexamethasone
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The current study was designed to evaluate the anti-inflammatory effect of GKB in the rat model of granulomatous inflammation. Thirty rats were distributed into five groups:  The first group served as negative control group that received distilled water (DW) only without inducting inflammation, positive control group; treated with DW with the induction of inflammation and they were assigned to cotton pellet-induced granuloma, ginkgo biloba (GKB) treated group (200mg/kg/day), dexamethasone-treated group (1mg/kg), and Prednisolone treated group (5mg/kg). All the treatments were given orally for seven consecutive days.  On day eight, the rats were anesthetized and the pellets together with granulation tissue were carefully removed

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Publication Date
Sun Dec 01 2024
Journal Name
Toxicology Reports
The impact of methamphetamine on liver injury in Iraqi male addicts
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Publication Date
Mon May 01 2017
Journal Name
The Journal Of Immunology
Protective effects of Δ9-Tetrahydrocannabinol (THC) results from alteration in lung dysbiosis mediated by SEB-induced acute lung injury
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Abstract<p>Inhalation of Staphylococcal Enterotoxin B (SEB) is known to induce acute lung injury (ALI) and studies from our laboratory have shown that THC, a psychoactive ingredient found in Cannabis sativa, can attenuate the ALI. In the current study, we investigated the role played by lung microbiota in ALI with or without THC treatment. A dual-dose of SEB was given to C3H/HeJ mice, which were then treated either with vehicle or THC. SEB-administration caused ALI and 100% mortality while all THC-treated mice survived and suppressed the inflammation in the lungs. Furthermore, lung microbiota was collected and 16S rRNA sequencing was performed. The data were analyzed to determine the alpha and b</p> ... Show More
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Publication Date
Thu Jan 30 2014
Journal Name
Al-kindy College Medical Journal
Effects of Sleeve Gastrectomy as a Bariatric Surgery on Weight of Dietary Induced Obese Rats.
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Background: Obesity is becoming the healthcare epidemic world wide.Obesity is associated with reduced life expectancy, increased morbidity and mortality, and greater healthcare costs.Bariatric surgery is the only effective treatment for morbid obesity and is gaining increasing popularity. There has been a steady rise in the numbers and types of bariatric operations done worldwide in recent years butnon of prove to be ideal .Animal studies and use of animal models are significant element in the evolution of medical knowledge and the use of animals as a model for bariatric surgery is of importance to study the mechanisms of these operationsa and also help to develop new technique in management of obesity.Objectives:Study of effects of slee

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Publication Date
Tue Mar 12 2024
Journal Name
Biomolecules
Limonene Exerts Anti-Inflammatory Effect on LPS-Induced Jejunal Injury in Mice by Inhibiting NF-κB/AP-1 Pathway
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The human gastrointestinal system is a complex ecosystem crucial for well-being. During sepsis-induced gut injury, the integrity of the intestinal barrier can be compromised. Lipopolysaccharide (LPS), an endotoxin from Gram-negative bacteria, disrupts the intestinal barrier, contributing to inflammation and various dysfunctions. The current study explores the protective effects of limonene, a natural compound with diverse biological properties, against LPS-induced jejunal injury in mice. Oral administration of limonene at dosages of 100 and 200 mg/kg was used in the LPS mouse model. The Murine Sepsis Score (MSS) was utilized to evaluate the severity of sepsis, while serum levels of urea and creatinine served as indicators of renal f

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Publication Date
Sun Jan 01 2023
Journal Name
Journal Of Medicine And Life
Evaluating the renoprotective effects of omega-3-6-9 against cisplatin-induced nephrotoxicity in mice
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Fatty acids, particularly omega-3, omega-6, and omega-9, play a vital role in various biological processes. As the body cannot synthesize omega-3 and omega-6, dietary sources of these fatty acids are essential. Each omega fatty acid has a distinct chemical structure, source, and function. Cisplatin (CP) treatment is known to cause acute kidney injury (AKI) due to its inflammatory effects. This study explored the renoprotective potential of omega-3-6-9 when co-ad-ministered with cisplatin in a mice model. We divided adult mice into five groups: a control group received 0.5 ml of liquid paraffin; a cisplatin-only group; two groups were treated with low (50 mg/kg) and high (100 mg/kg) doses of omega-3-6-9 plus cisplatin; and a final group rece

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