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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
Tue Oct 29 2024
Journal Name
Journal Of Advanced Pharmacy Education And Research
Evaluating the effects of different doses of fimasartan on methotrexate-induced renal inflammation in rats
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The nephrotoxicity induced by methotrexate is a severe condition that greatly affects its therapeutic potential and has a significant inflammatory component. Fimasartan is an angiotensin receptor blocker that offers organ-protective effects and may be useful in mitigating renal injury. The present study explored the anti-inflammatory potential of two doses of fimasartan against methotrexate-mediated nephrotoxicity. Albino rats were intraperitoneally administered a single methotrexate (20 mg/kg). Intraperitoneal treatment with fimasartan (5 or 10 mg/kg/day) was initiated on day two after methotrexate injection and continued for seven consecutive days. Methotrexate significantly increased serum urea, creatinine, and NGAL concentrations. It al

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Publication Date
Thu Oct 29 2020
Journal Name
Toxicological Research
Liver functions in combined models of the gentamicin induced nephrotoxicity and metabolic syndrome induced by high fat or fructose diets: a comparative study
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Publication Date
Fri Mar 31 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Therapeutic Use of Silymarin in the Management of Suspected Renal and Hepatic Injury Produced by NSAIDs in Osteoarthritis Patients
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Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) mostly associated with renal and hepatic adverse effects, and the adjunct use of compounds with potent protective effects, like silymarin, may be one of the choices to avoid these effects. This project was designed to evaluate the protective effect of silymarin against the suspected renal and hepatic injury induced with long term use of NSAIDs; 220 patients with osteoarthritis were randomized into 5 groups and treated with either silymarin 300mg/day alone, piroxicam 20mg/day alone, meloxicam 15mg/day alone or the combination of each of them with silymarin for 8 weeks. The renal and hepatic functions were evaluated before starting treatment and after 8 weeks including assessm

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Publication Date
Mon Apr 01 2024
Journal Name
Iop Conference Series: Earth And Environmental Science
Effect of Inhalation Exposure to Nano-Imidacloprid on Liver and Kidney Functions In Male Rats
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Abstract<p>Pesticide poisoning is a serious global public health issue and is responsible for a sizable number of annual fatalities. This study was designed to examine the potentially harmful effects of adult rats being exposed to imidacloprid (IMD) as a nanoparticle by determining the chronic effect of inhalation of (5,10 and 20) mg/kg/b.w. of nano-imidacloprid for a duration of 60 days. The most important biochemical parameters of the serum liver function parameters were aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ALP, kidney function [blood urea, creatinine, and urea], and oxidative stress parameters (MDA, GSH, and CAT) in all treated groups when</p> ... Show More
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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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Publication Date
Mon Dec 23 2019
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Effects of Omega-3 Co-Administered with Therapeutic Dose of lornoxicam on Male Rats' Liver
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The purpose of this study was to investigate the effect of omega-3 poly unsaturated fatty-acids co-administered with the therapeutic dose of lornoxicam on liver of healthy rats. Twenty-eight adults male rats weighing 180-200g were used in this study and the animals were randomly divided into four groups of seven rats each. Group I: negative control/rats intraperitoneally injected with normal saline in a dose 5ml/kg/day; Group II: rats intraperitoneally injected with lornoxicam at dose 0.7 mg/kg/day; Group III: rats orally-administered omega-3 only at a dose 185mg/kg/day; Group IV: rats co-administered omega-3 (185mg/kg/day) orally and in

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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
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
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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