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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
Mon May 16 2022
Journal Name
International Journal Of Biomaterials
Histopathological and Biochemical Comparative Study of Copper Oxide Nanoparticles and Copper Sulphate Toxicity in Male Albino Mice Reproductive System
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Copper (Cu) is an essential trace element for the efficient functioning of living organisms. Cu can enter the body in different ways, and when it surpasses the range of biological tolerance, it can have negative consequences. The use of different nanoparticles, especially metal oxide nanoparticles, is increasingly being expanded in the fields of industry and biomedical materials. However, the impact of these nanoparticles on human health is still not completely elucidated. This comparative study was conducted to evaluate the impacts of copper oxide nanoparticles (CuO NPs) and copper sulphate (CuSO4 0.5 (H2O)) on infertility and reproductive function in male albino mice BALB/c. Body weight, the weight of male reproductive organs, mal

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Publication Date
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Possible Cardiac Adverse Effects Induced by Therapeutic Doses of Ciprofloxacin in Juvenile Rats
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Ciprofloxacin is widely used in treating adults infected with Gram-negative bacteria. It is contraindicated in children, growing adolescents and during pregnancy due to joint toxicity. Its toxicity concerning other organs needs to be clarified. Thus, this study was designed to study the possible cardiac damage induced by two selected doses of ciprofloxacin in juvenile rats.Eighteenth healthy juvenile rats (4 weeks old and their weight 30 ± 2 gm) were utilized in this study and divided into three groups. Group-I control; group II and group III, respectively injected IP with 25 mg/kg and 50 mg/kg ciprofloxacin every 12 hours for one week. Serum enzymes activities alanine aminotransferase (ALT), aspartate aminotransferase  (AST), cr

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Publication Date
Mon Oct 16 2017
Journal Name
Int. J. Pharm. Sci. Rev. Res.
The Effects of Vitamin D on L-arginine-induced Acute Pancreatitis in Rats
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This study was aimed to investigate the protective effect of vitamin D on L-arginine induced acute pancreatitis in rats. Twenty eight white Albino rats of both sexes were divided into 4 equal groups. Negative control rats (group I) intra-peritoneally injected with normal saline, positive control (group II) rats induced acute pancreatitis with L- arginine, group III rats treated with a single dose of vitamin D, and group IV treated with single dose of vitamin D prior to first dose of L- arginine. Serum amylase, lipase and cytokines such as tumour necrosis factor –alpha (TNF-α), interleukin-1 beta (IL1β); in addition, my eloperoxidase (MPO) enzyme activity in the pancreas were measured. In acute pancreatitis group (group II), there was a

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Publication Date
Sat Jun 03 2023
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn: 2789-3219 )
Analyzing the Potential Antioxidative Effects of Omega-369 in Preventing Acetaminophen-Induced Liver Damage
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Background: As acetaminophen (APAP) toxicity has become more common in many countries, related cases of poisoning, whether deliberate or unintentional, have been identified as a key contributor to acute liver failure. Aime: To discover if omega-369 fatty acids could protect the liver of male mice from the effects of acetamiophen. Methods: Thirty-five albino male mice were allocated to one of five groups at random. Group 1 served as the "negative control" and received a single intraperitoneal injection (10 ml/kg) of normal saline on the eleventh day of the test following ten days of receiving liquid paraffin orally at a dose of 10 ml/kg. The liquid paraffin was given to group 2 "positive control". Group 3 received Omega 369 (50 mg/kg

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Publication Date
Sat Oct 01 2022
Journal Name
Baghdad Science Journal
Effect of Alstonia Boonei Stem Bark Extracts on the Activity of Liver Maker Enzymes in Rats Induced by Ccl4
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This study investigated the outcome of Alstonia boonei stem bark on liver enzymes after inducing the Wistar albino rats with carbon tetrachloride (CCl4). This effect of plant extract was compared with silymarin – a drug commonly used for the treatment of chronic hepatocyte disorder. The plant sample was extracted with ethanol; acute toxicity study of the extract was performed on eighteen Wistar mice, while 30 rats were sacrificed for liver enzymes assay. The rats were divided into six clusters: each cluster has five rats, culster 1 served as control and was given 2 mL/kg b.w - distilled water; clusters 2 – 6 were CCl4 induced. Cluster 2 was untreated but served as the negative control while cluster 3 wa

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Publication Date
Mon Jun 12 2023
Journal Name
Frontiers In Pharmacology
Protective effect of cafestol against doxorubicin-induced cardiotoxicity in rats by activating the Nrf2 pathway
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Doxorubicin (DOX) is an efficient antineoplastic agent with a broad antitumor spectrum; however, doxorubicin-associated cardiotoxic adverse effect through oxidative damage and apoptosis limits its clinical application. Cafestol (Caf) is a naturally occurring diterpene in unfiltered coffee with unique antioxidant, antimutagenic, and anti-inflammatory activities by activating the Nrf2 pathway. The present study aimed to investigate the potential chemoprotective effect of cafestol on DOX-induced cardiotoxicity in rats. Wistar albino rats of both sexes were administered cafestol (5 mg/kg/day) for 14 consecutive days by oral gavage alone or with doxorubicin which was injected as a single dose (15 mg/kg intraperitoneally at day 14) to i

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Publication Date
Sat Dec 24 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Possible protective effects of two different doses of cyanocobalamin against methotrexate nephrotoxicity in rats
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Abstract

   Nephrotoxicity is defined as rapid deterioration in kidney functions. It arises from direct exposure to drugs or their metabolites. Methotrexate is a famous chemotherapeutic drug with anti-inflammatory and immunosuppressive properties. A high-dose methotrexate-induced renal dysfunction can be life threatening. Cyanocobalamin, one of the forms of vitamin B12, acts as a coenzyme in the conversion of homocysteine to methionine in the cytosol, and the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondrion. This study is designed to examine the effect of cyanocobalamin in two different doses each co-administered with methotrexate at 20 mg/kg induced nephrotoxicity in rat

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Publication Date
Sat Dec 24 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Possible protective effects of two different doses of cyanocobalamin against methotrexate nephrotoxicity in rats
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Abstract    Nephrotoxicity is defined as rapid deterioration in kidney functions. It arises from direct exposure to drugs or their metabolites. Methotrexate is a famous chemotherapeutic drug with anti-inflammatory and immunosuppressive properties. A high-dose methotrexate-induced renal dysfunction can be life threatening. Cyanocobalamin, one of the forms of vitamin B12, acts as a coenzyme in the conversion of homocysteine to methionine in the cytosol, and the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondrion. This study is designed to examine the effect of cyanocobalamin in two different doses each co-administered with methotrexate at 20 mg/kg induced nephrotoxicity in rats through the involvement of Nrf2

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Publication Date
Fri Jun 01 2018
Journal Name
Journal Of Global Pharma Technology
Hepatoprotective Potentials of Menaquinone Doxorubicin Associated Hepatotoxicity 7 against
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Dox, is still widely used in modern cancer treatments for different type of malignancy despite the advent of targeted therapy. However, its beneficial effect was limited by its toxicity on various organs. The objective of this study was to investigate the hepatoprotective effect of menaquinone-7 against hepatotoxicity induced by doxorubicin in rats. Sixty adult rats of both sexes were used in this study; the animals were randomly enrolled into six groups of 10 animals each. Group I: negative control; Group II: Menaquinones-7 at a dose of 16µg/kg; Group III: Menaquinones-7 at a dose of 48µg/kg; Group IV: positive control (Doxorubicin 15mg/kg); Group V: Menaquinones-7 at a dose of 16µg/kg administered prior to a single dose of Doxorubicin

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Publication Date
Mon Jan 01 2024
Journal Name
Current Research In Pharmacology And Drug Discovery
Hepatoprotective effect of Nobiletin against 5-fluorouracil induce hepatotoxicity
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5-florouracil is a widely used anticancer/anti-metabolite drug used to treat solid tumor like colon cancer, head and neck, rectum, stomach, pancreas and breast cancer; but, it can cause hepatotoxicity by induction of apoptosis through activation of caspases enzymes and oxidative stress. Nobiletin is a citrus fruit-derived flavonoid that possess significant biological activity, including anticancer, and anti-inflammatory. This study was design to investigate the effects of nobiletin against 5-florouracil-indcued hepatotoxicity in male rats through the measurement of selected -inflammatory, -apoptosis, and -oxidative stress markers. By use male Albino rats weighing 150-250gm around 28 animals; giving them tap water ad libitum and fed commerci

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