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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
Sun Jul 30 2023
Journal Name
Al-rafidain Journal Of Medical Sciences
Correlation of Kidney Injury Molecule-1 and Nephrin Levels in Iraqi Patients with Diabetic Nephropathy
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Diabetic nephropathy is characterized by persistent microalbuminuria and metabolic changes that decline renal functions. Researchers have been prompted to explore new biomarkers such as KIM-1 and nephrin that may enhance the identification of disease. Objective: To Evaluate biomarker levels of kidney injury molculre-1 (KIM-1) concentration and nephrin as early and sensitive markers of nephropathy in type 2 diabetic patients. Method: One hundred T2DM patients were included in a cross-sectional study at the specialized center for endocrinology and diabetes, Baghdad. The first group includes 50 diabetic nephropathy (DN) patients, and the second group includes 50 T2DM patients without DN. Biochemical and clinical parameters were reported for pa

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Publication Date
Sat Dec 11 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Ameliorative Effects of the Aqueous Extract of Allium porrum (Wild Leek) against Cisplatin-Induced Nephrotoxicity in Rabbits
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The aim of the present study was to investigate the nephroprotective, hypolipidemic and hypoglycemic effects of Allium porrum (leek) in rabbits with cisplatin nephrotoxicity. Forty adult male New Zealand rabbits were divided randomly into four groups (ten rabbits in each group) as follows: Group I: (negative control) (C) received oral daily dose of distilled water for 15 successive days. Groups II: (Leek) (L) received oral daily dose of aqueous leek extract (500mg/kg/day) for 15 successive days. Group III: (positive control) [cisplatin (CP)] received oral daily dose of distilled water for 15 successive days, and subsequently administered single dose of Cisplatin (3.5mg/kg/day) by intraperitoneal injection from day 10 for five da

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Publication Date
Sun Dec 04 2011
Journal Name
Baghdad Science Journal
Effect of Hyper and Hypothyroidism on Lipid Profile and Liver Function of Male Rats
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This study was designed to investigate the effect of thyroid hormone disturbance on lipids profiles and liver functions. Eighteen mature male rats Rattus norvegicus were divided into three groups. The first and the second groups were injected subcutaneously with thyroxine (T4) and carbimazol (both at 600 µg/kg BW) respectively on alternate days, to produce recurrent periods of hyper and hypothyroidism .The control group which is the third group was injected with physiological saline. The process continued 4 weeks, after that, injection, blood specimens were collected to estimate serum levels of T3 and T4, Total cholesterol (TC), Triglycerides (TG), High density lipoprotein cholesterol (HDL-C), Low density lipoprotein cholesterol (LDL-C) an

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Publication Date
Fri Oct 02 2026
Journal Name
Advances In Environmental Biology
A study effect of thyme on biochemical and histological changes in liver of male rats
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Publication Date
Thu May 15 2025
Journal Name
Journal Of Animal Health And Production
Functional and Histological Study of Liver in Adult Rats Treated with Different Doses of Melatonin
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his study aimed to evaluate the effects of different doses of melatonin on liver function in adult rats. Eighteen Wistar adult albino rats (Rattus norvegicus), approximately 13–16 weeks old and weighing 230 ± 10 g, were randomly divided into three groups (n=6 per group) and treated orally for 30 days as follows: Group A1 received 10 mg/kg body weight (B.W) of melatonin; Group A2 received 20 mg/kg B.W of melatonin; and the control group (Group A) received distilled water. At the end of the treatment period, blood samples were collected via cardiac puncture, and serum was separated for biochemical analysis. Parameters assessed included oxidative stress markers (malondialdehyde (MDA), reduced glutathione (GSH)) and liver enzymes (aspa

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Publication Date
Sun Jan 01 2023
Journal Name
International Journal Of Drug Delivery Technology
Protective Effects of Aqueous Cranberry Fruit Extract against Genotoxicity Induced by Cisplatin in Mice Bone Marrow Cells
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The cranberry (Vaccinium macrocarpon) is a North American native fruit and contains a very wide variety of phytochemicals, which has several beneficial effects on humans. Aim: The study was designed to assess the protective effect of cranberry fruit extract on selected genotoxic parameters induced by cisplatin in mice’s bone marrow. Methods: 56 male albino mice were randomLy divided into two equal numbers (28 mice) for each part of the study [Part one: for the evaluation of chromosomal aberrations and the mitotic index; and Part two: for the evaluation of micronucleus index]; and for each part, mice were randomly divided into 4 groups: Group I [negative Control/orally-administered normal saline]; Group II [Orally-administered cranberry fr

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Publication Date
Thu Jun 25 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Effects of Two Different Doses of Zinc Sulfate on Serum Troponin I 3 Enzyme Level and Cardiac Malondialdehyde Contents in Mitoxantrone-Induced Cardiotoxicity in Rats
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Abstract

   Mitoxantrone is an antitumor agent used in the treatment of breast and prostate cancer, acute leukemia, lymphoma, and also in the treatment of multiple sclerosis due to its immunosuppressive properties. The mitoxantrone's cardiotoxicity is irreversible, dose-dependent, and it may occur years after treatment. Zinc is considered as an essential mineral for cell division and the synthesis of DNA and protein; furthermore, such mineral has an important role in states of cardiovascular diseases; and may have protective effects in coronary artery disease and cardiomyopathy.

Objective: The current study is designed to investigate effects of two different doses of zinc sulfat

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Publication Date
Thu Jun 25 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn: 1683 - 3597 , E-issn : 2521 - 3512)
Effects of Two Different Doses of Zinc Sulfate on Serum Troponin I 3 Enzyme Level and Cardiac Malondialdehyde Contents in Mitoxantrone-Induced Cardiotoxicity in Rats
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Abstract    Mitoxantrone is an antitumor agent used in the treatment of breast and prostate cancer, acute leukemia, lymphoma, and also in the treatment of multiple sclerosis due to its immunosuppressive properties. The mitoxantrone's cardiotoxicity is irreversible, dose-dependent, and it may occur years after treatment. Zinc is considered as an essential mineral for cell division and the synthesis of DNA and protein; furthermore, such mineral has an important role in states of cardiovascular diseases; and may have protective effects in coronary artery disease and cardiomyopathy. Objective: The current study is designed to investigate effects of two different doses of zinc sulfate on mitoxantrone-induced cardiotoxicity

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Publication Date
Wed Sep 27 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of Anti-inflammatory Effects of Cinnamic Acid Against Dextran Sodium Sulfate Induced Ulcerative Colitis in Male Mice
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Inflammatory bowel disease (IBD) is a common chronic inflammatory disease of the gastrointestinal tract, including ulcerative colitis and Crohn's disease. ulcerative colitis (UC)  disease is characterized by chronic, persistent, recurrent, and nonspecific intestinal ulcers and mucosal inflammation. This study investigated the protective effects of cinnamic acid on dextran sodium sulfate (DSS) induced ulcerative colitis in mice. Forty adult male mice were collected and randomly divided into five groups, group Ӏ received a suspension of distill water and poloxamer, and group ӀӀ received 3% DSS in drinking water for 7 consecutive days. Two treatment groups received an oral suspension of cinnamic acid 50 and 25 mg/kg respectively an

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Publication Date
Wed Oct 07 2020
Journal Name
Indian Journal Of Forensic Medicine &amp; Toxicology
Association Between Carbamazepine Toxicity, Liver Bile Duct Injury, Granuloma and Inflammatory Cells Infiltration in Female Mice
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The liver is an important organ in the body that can be affected by many drugs and toxins. The hepatotoxins can cause oxidant stress that lead to activation of inflammatory cells and cause liver damage. Drug induced bile duct injuries are related to drug toxicity, multiple drugs have been known to cause the development of liver granulomas. Carbamazepine (CBZ) among other antiepileptic drugs is believed to cause hepatic injury. In this study we investigated the effect of (CBZ) 20mg/kg/day on female mice liver after 14 and 30 days of treatment. The histological findings showed that (CBZ) can cause histological alterations in the liver components such as bile duct proliferation, biliary hypertrophy, ductopenia, inflammatory cells infiltration

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