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Comparative Hepatoprotective Effects of Dapagliflozin to Silymarin Against Cyclophosphamide-Induced Liver Injury in Rats: Biochemical, Antioxidants and Histopathological Studies
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Introduction. Hepatotoxicity is primarily-caused by oxidative stress and mitochondrial dysfunction; and, it is the principal factor that restricts the clinical efficacy of cyclophosphamide (Cpd), which is a chemotherapeutic drug that is frequently-used. The antioxidant capabilities have been demonstrated by dapagliflozin (Dapa), which is an inhibitor of sodium-glucose co-transporter-2 (SGLT2). Silymarin (Sil) is a chemical that is extracted from milk thistle. Researches have demonstrated that silymarin has hepatoprotective and antioxidant properties.

Aim. This study aimed to compare the hepatoprotective effects of dapagliflozin to silymarin in a rat model of Cpd-induced liver injury.

Material and methods. Negative control, vehicle (2 % aqueous sodium carboxy methylcellulose CMC), Cpd (30 mg/kg/ day, Intraperitoneal (ip), Dapa + Cpd (3 mg/kg/day, oral), and Sil + Cpd (200 mg/kg/day, oral) were the five groups that were randomly assigned to fifty rats. Each group consisted of ten rats. Following a period of ten days, evaluation the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum; while, malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) enzyme were all measured in liver tissues; and histological inspection was also performed on the samples.

Results and discussion. Levels of ALT, AST, and MDA were each considerably-increased by Cpd, while the levels of GSH and SOD were decreased ( P < 0.05). Treatment with either Dapa or Sil each with Cpd resulted in a significant amelioration of these alterations ( P < 0.05 compared to controls). The results of the study demonstrate that Dapa was more effective than Sil in lowering MDA levels and increasing of GSH and SOD levels ( P < 0.05). In the Dapa (Group IV), the histological examination revealed that the hepatic architecture had been intact, and there was only slight increase in vascular congestion.

Conclusion. Both dapagliflozin and silymarin each confer comparable hepatoprotective effects against Cpd-induced liver injury, possibly through attenuation of oxidative stress and preservation of hepatocyte integrity. The study adds to current evidence supporting the use of each of these agents in hepatic injury models. However, unlike the study of Satyam et al (2024) which investigated their combined effect, this study highlights their individual efficacy in a cyclophosphamide-specific toxicity model.

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Publication Date
Wed Jun 24 2026
Journal Name
Iraqi Journal Of Pharmaceutical Sciences
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 liv

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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)
The Safranal Effect against Cyclophosphamide-Induced Liver Injury
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The liver is the primary organ for drug metabolism, elimination, Cyclophosphamid is the classical alkylating agent nitrogen mustard, its metabolism into two cytotoxic metabolites, and increase reactive oxygen species that is make liver toxicity. Safranal as the most abundant chemical in saffron essential oil, it have anti-oxidant, anti-inflammatory, antiapoptic and free radical scavenger activity. The aim of study is to assess the protective effects of safranal on the cyclophosphamide-induce liver toxicity in rat model. This occur by using five different groups of rats; control group, treatment group, cyclophosamide group (intraperitoneal i.p), cyclophosamide and (50mg and 100mg) oral safranal treatment groups. This study showed this pro

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Publication Date
Mon Oct 13 2025
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn 2789-3219 )
Protective Effects of Irigenin against Cyclophosphamide-induced Nephrotoxicity in Male Rats: Comparative Study with Vitamin E
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Background: Cyclophosphamide is an alkylating agent that is effective against a broad spectrum of tumors, with nephrotoxicity as a side effect. Irigenin is a natural isoflavonoid isolated from the rhizome of Belamcanda chinensis that has been reported to exert antioxidant activities. Objective: Evaluating the possible protective effects of irigenin on cyclophosphamide-induced nephrotoxicity in male rats. Methods: Fifty apparently healthy male albino rats were divided into five groups: (control, induction, irigenin, irigenin with cyclophosphamide, and vitamin E with cyclophosphamide. At the end of the experiment (day 29), all rats were sacrificed. Different parameters were evaluated, including urea and creatinine serum concentration,

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Publication Date
Tue Jul 08 2014
Journal Name
African Journal Of Traditional, Complementary And Alternative Medicines
Hepatoprotective Effect Of &lt;i&gt;Cymbopogon Citratus&lt;/i&gt; Aqueous Extract Against Hydrogen Peroxide-Induced Liver Injury In Male Rats
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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Hepatoprotective Effect of the Aqueous Extract of Camellia sinensis Against Methotrexate-induced Liver Damage in Rats
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Methotrexate (MTX) is a folate antagonist widely used in the treatment of neoplastic diseases; its biotransformation in the liver produced active metabolites that promote hepatotoxicity. The present study was designed to evaluate the hepatoprotective effect of aqueous extract of Camellia sinensis (Green tea) against MTX-induced liver damage in rats. A model of liver injury in rats was induced by intraperitoneal injection of 20mg/kg MTX as a single dose followed by saline and 1.25% and 2.5% aqueous extract of green tea (GTE) were orally administered 7 days prior and 5 days after MTX-intoxication as a sole source of drinking water. After killing the animals, blood samples were obtained for evaluation of serum levels of alanine and

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Publication Date
Tue Jan 01 2019
Journal Name
Biomedical & Pharmacology Journal
Antioxidants and Hepatoprotective Studyof a Purified Bauhinia Variegate Leaves and Flowers against Carbon Tetrachloride-Induced Toxicity in Experimental Rats
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This study was designed to investigate the hepatoprotective activity and antioxidant enzymes of purified Bauhinia variegate leaves extract and purified flowers extract were administered (200 mg/kg, orally once daily) to reduce the effect of carbon tetrachloride-damage in rat’sliver for three weeks. Thereafter, the levels of some serum biochemical factorssuch as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase,and the activity of three different antioxidant enzymes (glutathione, superoxide dismutase, and catalase) were investigated.Liver homogenate can used to estimated antioxidant parameters: glutathione, superoxide dismutase and catalase. The purified Bauhinia variegate leaves and purified flowers significantly

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Publication Date
Fri Jun 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Study The Lung-Protective Effects of Riboflavin and Cyanocobalamin Against Lung Toxicity-Induced by Cyclophosphamide in Rats
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Cyclophosphamide (CP) is a cytotoxic alkylating agent it's used associated with different side effects including lung toxicity. Vitamin B2 and vitamin B12 have lung-protective effects. This study was designed to evaluate lung-protective effects of both vitamins against lung toxicity induced by cyclophosphamide. seventy healthy adult albino male and female rats divided into seven groups each group containing ten rats were used in the present study and treated for seven days. On day eight rats were sacrificed and serum was obtained for glutathione and total antioxidant capacity measurement and lung extracted for immunohistochemical study; both vitamins significantly (P<0.05) increased glutathione and total antioxidant capacity in compar

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Publication Date
Thu Dec 28 2023
Journal Name
The Iraqi Journal Of Veterinary Medicine
Resveratrol Administration Ameliorates Hepatotoxicity in Mercuric Chloride-‎Induced Liver Injury in Rats
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Mercuric chloride (HgCl2) pollution and poisoning has been a worldwide health ‎concern for decades, especially after the industrial revolutions. The aim of this study ‎was to investigate the role of resveratrol in reversing the deleterious effects of ‎HgCl2 exposure to resume the normal functions of hepatocyte. To achieve the study, ‎mature Sprague Dawley rats were assigned to five groups. Negative control group ‎‎(C) kept without any treatment; vehicle-treated group (D) received dimethyl ‎sulfoxide (DMSO); resveratrol-treated group (R), received 100 mg/kg of resveratrol; ‎HgCl2-intoxicated group (HD), received i.p. injection of HgCl2 at a dose of 1 mg/kg ‎for 30 consecutive days along to oral gavage of DMSO; and finally H

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Publication Date
Tue Jan 20 2026
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Effects of a Chelated Multi-Micronutrient Nanofertilizer on the Liver ofAlbino Rats: A Biochemical and Histopathological Assessment
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Nanofertilizers offer a promising solution to increase crop yields amid increasing population pressure. Yet  there have been safety concerns about their use, particularly in challenging conditions. This work was designed to assess the toxicological effects of a chelated multi-micronutrient nanofertilizer on albino rats (Rattus norvegicus) as non-target organisms, focusing on the liver, which has important metabolic functions. Thirty-five animals were weighed and randomly divided into 5 groups (n=7). A negative control group was included, and four experimental groups (C1-C4) were given the test item. The dosing regimen for the experimental groups was 15 oral doses of nanofertilizer every other day for 29 days. All the groups were

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Preventive Effects of Different Doses of Pentoxyfilline Against CCl4-Induced Liver Toxicity in Rats
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The liver protective effects of pentoxifylline were studied through pre-treatment of rats with various intraperitoneal (IP) doses (25, 50 and 100mg/kg/day) 14 days before induction of liver toxicity by carbon tetrachloride (CCl4). The parameters of oxidative stress, malondialdehyde (MDA) and reduced glutathione (GSH) were measured in liver homogenate in addition to histopathological examinations.  Analysis of data revealed significant amelioration of oxidative stress in groups of animals pre-treated with different doses of pentoxifylline (PTX) compared to group of animals intoxicated by CCl4 as evidenced by lowering MDA contents and elevation of GSH levels in liver tissue homogenate but the levels still signifi

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