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  • 1
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    Online Resource
    Thymoquinone, but Not Metformin, Protects against Gentamicin-Induced Nephrotoxicity and Renal Dysfunction in Rats
    MDPI AG ; 2021
    In:  Applied Sciences Vol. 11, No. 9 ( 2021-04-27), p. 3981-
    Details
    In: Applied Sciences, MDPI AG, Vol. 11, No. 9 ( 2021-04-27), p. 3981-
    Abstract: Background: Gentamicin (GM) is an antibiotic that is widely used to treat many Gram-negative bacteria, such as those involved in urinary tract infections. However, being nephrotoxic, GM dose adjustment and reno-protective elements must be concurrently administered with GM to minimize kidney damage. Oxidative stress plays a pivotal role in the pathogenesis of GM-induced nephrotoxicity. Thymoquinone (TQ) is a promising therapeutic substance, that is being extensively studied in many diseases, such as diabetes mellitus, cancer, hypertension, and others. The powerful antioxidant properties of TQ may greatly help in minimizing GM nephrotoxicity. Metformin (MF) is a well-known, clinically approved oral hypoglycaemic drug that has many other actions, including antioxidant properties. The aim of this work was to evaluate the possible antioxidant and reno-protective effects of TQ and metformin in GM-induced nephrotoxicity in the same model (rats) at the same time. In addition, we aimed to further understand the effects underlying GM-induced nephrotoxicity. Methods: Twenty male rats were randomly divided into four equal groups: the first group (control) received distilled water; the second group received GM only; the third group received concurrent oral TQ and GM; and the fourth group received concurrent oral MF and GM. After 4 weeks, renal function and histopathology, as well as levels of the oxidative markers glutathione peroxidase-1 (GLPX1), superoxide dismutase (SOD), and malondialdehyde (MDA) in the kidney tissues, were assessed. Results: Compared with the control group, and as expected, the GM-injected rats showed significant biochemical and histological changes denoting renal damage. Compared with GM-injected rats, the concurrent administration of TQ with GM significantly reduced the levels of serum creatinine, serum urea, and tissue MDA and significantly increased the levels of GLPX1 and SOD. Concurrent metformin administration with GM significantly increased the levels of both GLPX1 and SOD and significantly decreased the levels of tissue MDA but had no significant effect on serum creatinine and urea levels. Compared with GM-injected rats, the addition of either TQ or MF resulted in a reduction in endothelial proliferation and mesangial hypercellularity. Conclusions: Both TQ and MF effectively alleviated the oxidative stress in GM-induced nephrotoxicity in rats, with TQ but not MF producing a complete reno-protective effect. Further studies for evaluation of different reno-protective mechanisms of TQ should be conducted.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    URL: Article
    DOI: 10.3390/app11093981
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2704225-X
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  • 2
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    Online Resource
    Quercetin attenuated ischemic stroke induced neurodegeneration by modulating glutamatergic and synaptic signaling pathways
    Elsevier BV ; 2024
    In:  Heliyon Vol. 10, No. 7 ( 2024-04), p. e28016-
    Details
    In: Heliyon, Elsevier BV, Vol. 10, No. 7 ( 2024-04), p. e28016-
    Type of Medium: Online Resource
    ISSN: 2405-8440
    URL: Article
    DOI: 10.1016/j.heliyon.2024.e28016
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 2835763-2
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  • 3
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    The Protective Effect of Green Tea Extract against Lead Toxicity in Rats Kidneys
    OMICS Publishing Group ; 2014
    In:  Asian Journal of Biomedical and Pharmaceutical Sciences Vol. 4, No. 39 ( 2014-12-27), p. 30-34
    Details
    In: Asian Journal of Biomedical and Pharmaceutical Sciences, OMICS Publishing Group, Vol. 4, No. 39 ( 2014-12-27), p. 30-34
    Type of Medium: Online Resource
    ISSN: 6299-722X
    Uniform Title: English
    URL: Issue
    URL: Journal
    URL: Article
    DOI: 10.15272/ajbps.v4i39
    DOI: 10.15272/ajbps
    DOI: 10.15272/ajbps.v4i39.648
    Language: Unknown
    Publisher: OMICS Publishing Group
    Publication Date: 2014
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  • 4
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    Neuroprotective Effect of Clobenpropit against Lipopolysaccharide-Induced Cognitive Deficits via Attenuating Neuroinflammation and Enhancing Mitochondrial Functions in Mice
    MDPI AG ; 2021
    In:  Brain Sciences Vol. 11, No. 12 ( 2021-12-08), p. 1617-
    Details
    In: Brain Sciences, MDPI AG, Vol. 11, No. 12 ( 2021-12-08), p. 1617-
    Abstract: Clobenpropit (CLO), an antagonist on histamine H3 receptors (HH3R), has been shown to protect NMDA-induced neuronal necrosis in cortical neuronal cell culture from rats. In this work, we explored its potential on lipopolysaccharide (LPS)-induced memory deficits, neuroinflammation, and mitochondrial dysfunction in mice. CLO (1 and 3 mg/kg, p.o.) was treated continually for 30 days, and neurotoxicity was induced by four doses of LPS (250 µg/kg, i.p.). The radial arm maze (RAM) was used to access memory behaviors. After the REM test, brain tissue was collected from each mouse to estimate pro-inflammatory cytokines (TNFα and IL6), anti-inflammatory cytokines (TGF-β1 and IL-10), cyclooxygenase-2 (COX 2), and mitochondrial respiratory chain complex (MRCC- I, II and IV) enzymes. CLO treatment reversed the LPS-induced behavioral deficits by a significant reduction in time taken to consume all five bites (TTB), working memory error (WME), and reference memory error (REM) in the REM test. Regarding neuroinflammation, it attenuated the release of COX, TNF-α, and IL-6, and augmented TGF-β1 and IL-10 levels in the brain. Reversal of LPS-induced brain MRCC (I, II, and IV) levels also resulted with CLO treatment. From these findings, CLO promises neuroprotection against LPS-induced cognitive deficits by ameliorating neuroinflammation and restoring the MRCC enzymes in mice.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    URL: Article
    DOI: 10.3390/brainsci11121617
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2651993-8
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  • 5
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    Online Resource
    Therapeutic Potential of Human Mesenchymal Stem Cells Engineered with Different Concentrations of TNF α and IFNg
    American Scientific Publishers ; 2023
    In:  Journal of Biomaterials and Tissue Engineering Vol. 13, No. 5 ( 2023-05-01), p. 690-697
    Details
    In: Journal of Biomaterials and Tissue Engineering, American Scientific Publishers, Vol. 13, No. 5 ( 2023-05-01), p. 690-697
    Abstract: Aims: In this study, the authors aimed to examine the functional activities (adhesion, proliferation, and migration) of hMSCs under the effects of various concentrations of inflammatory mediators, such as TNF α or IFNg. Methods: HMSCs were exposed to various concentrations of the inflammatory mediators TNF α or IFNg, and the effects of TNF α or IFNg on the functional properties of hMSCs were determined using multiple functional assays (adhesion, proliferation, and migration). HMSC expression of genes (cytokine, chemokine, and adhesion molecule genes) was analyzed using real-time polymerase chain reaction (RT–PCR). Results: TNF α promoted their proliferation and migration especially at 100 ng/ml, while IFNg increased proliferation only at concentrations of 10 ng/ml and proliferation at 50 and 100 ng/ml. Conclusion: This study evaluated the suitability of hMSCs in treating inflammatory diseases, which are characterized by high levels of inflammatory mediators such as TNF α or IFNg, and proved that the treatment of hMSCs with TNF α or IFNg at higher concentrations has a protective effect.
    Type of Medium: Online Resource
    ISSN: 2157-9083
    URL: Article
    DOI: 10.1166/jbt.2023.3305
    Language: English
    Publisher: American Scientific Publishers
    Publication Date: 2023
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  • 6
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    Short-Term Treatment of Metformin and Glipizide on Oxidative Stress, Lipid Profile and Renal Function in a Rat Model with Diabetes Mellitus
    MDPI AG ; 2022
    In:  Applied Sciences Vol. 12, No. 4 ( 2022-02-15), p. 2019-
    Details
    In: Applied Sciences, MDPI AG, Vol. 12, No. 4 ( 2022-02-15), p. 2019-
    Abstract: Background: Oxidative stress, lipid profile and renal functions are well-known conventional risk factors for diabetes mellitus (DM). Metformin and gliclazide are popularly used monotherapy drugs for the treatment of DM. Aims: This study aims to assess the short-term treatment of single and dual therapy of glipizide/metformin on oxidative stress, glycemic control, serum lipid profiles and renal function in diabetic rats. Methods: DM was induced in rats with streptozotocin (STZ), then five different treatments were applied, including group I (untreated healthy control), group II (diabetic and untreated), group III (diabetic and treated with metformin), group IVI (diabetic and treated with glipizide) and group V (diabetic and treated with a combination of metformin and glipizide. Lipid peroxidation (LPO), nitric oxide (NO), total antioxidant capacity (TAC), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine and urea were measured. Results: Compared to the untreated DM group, FBG and HbA1c were significantly reduced in the DM groups (p 〈 0.01) treated with metformin (159.7 mg/dL & 6.7%), glipizide (184.3 mg/dL & 7.3%) and dual therapy (118 mg/dL & 5.2%), respectively. Treatment with dual therapy and metformin significantly decreased LPO and NO levels but increased TAC in diabetic rats more than glipizide compared to untreated diabetic rats. Furthermore, metformin (19.8 mg/dL, p 〈 0.001), glipizide (22.7 mg/dL, p 〈 0.001), and dual therapy (25.7 mg/dL, p 〈 0.001) significantly decreased urea levels in the treated rats compared to untreated DM rats (32.2 mg/dL). Both drugs and their combination exhibited a substantial effect on total cholesterol, HDL, LDL and atherogenic index. Conclusions: These results suggest that the therapeutic benefits of metformin and glipizide are complementary. Metformin exhibited superior performance in improving glycemic control and decreasing oxidative stress, while glipizide was more effective against dyslipidemia. These findings could be helpful for the treatment of future vascular patients, antilipidemic medicines and antioxidant therapy to improve the quality of life.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    URL: Article
    DOI: 10.3390/app12042019
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704225-X
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  • 7
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    α-Lipoic Acid Protects against Cyclosporine A-Induced Hepatic Toxicity in Rats: Effect on Oxidative Stress, Inflammation, and Apoptosis
    MDPI AG ; 2022
    In:  Toxics Vol. 10, No. 8 ( 2022-08-02), p. 442-
    Details
    In: Toxics, MDPI AG, Vol. 10, No. 8 ( 2022-08-02), p. 442-
    Abstract: The clinical application of cyclosporine A (CsA) as an immunosuppressive agent is limited by its organ toxicity. We aimed to evaluate the effectiveness of α-lipoic acid against CsA-induced hepatotoxicity and to delineate the underlying molecular mechanisms. Male Wistar rats (n = 24, 8 per each group) received the vehicle, CsA (25 mg/kg) and/or ALA (100 mg/kg, p.o.) for 3 weeks. Biochemical markers of liver function (serum ALT, AST, ALP 〈 GGT), oxidative stress (MDA, TAC, SOD, GSH, Nrf2/HO-1), inflammation (NF-κB, CD68, iNOS, NO, COX-2), and apoptosis (caspase-3) were assessed in serum and tissue. Liver histological analysis using H & E and Sirius red was performed. The development of liver injury in CsA-treated animals was indicated by elevated levels of liver enzymes, oxidants/antioxidants imbalance, inflammatory cells infiltration, up-regulated expression of inflammatory mediators, and apoptosis. These changes were associated with altered architecture of hepatic cells and fibrous connective tissue. ALA co-administration protected against CsA-induced liver damage and ameliorated biochemical changes and cellular injury. In conclusion, ALA demonstrated hepatoprotective potential against CsA-induced liver injury through combating oxidative stress, inflammation, and apoptosis, highlighting ALA as a valuable adjunct to CsA therapy.
    Type of Medium: Online Resource
    ISSN: 2305-6304
    URL: Article
    DOI: 10.3390/toxics10080442
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2733883-6
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  • 8
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    Online Resource
    Thymoquinone Lowers Blood Glucose and Reduces Oxidative Stress in a Rat Model of Diabetes
    MDPI AG ; 2021
    In:  Molecules Vol. 26, No. 8 ( 2021-04-17), p. 2348-
    Details
    In: Molecules, MDPI AG, Vol. 26, No. 8 ( 2021-04-17), p. 2348-
    Abstract: The aim of the present study was to assess the short-term effects of Thymoquinone (TQ) on oxidative stress, glycaemic control, and renal functions in diabetic rats. DM was induced in groups II and III with a single dose of streptozotocin (STZ), while group I received no medication (control). The rats in groups I and II were then given distilled water, while the rats in group III were given TQ at a dose of 50 mg/kg body weight/day for 4 weeks. Lipid peroxidase, nitric oxide (NO), total antioxidant capacity (TAC), glycated haemoglobin (HbA1c), lipid profiles, and renal function were assessed. Moreover, the renal tissues were used for histopathological examination. STZ increased the levels of HbA1c, lipid peroxidase, NO, and creatinine in STZ-induced diabetic rats in comparison to control rats. TAC was lower in STZ-induced diabetic rats than in the control group. Furthermore, rats treated with TQ exhibited significantly lower levels of HbA1c, lipid peroxidase, and NO than did untreated diabetic rats. TAC was higher in diabetic rats treated with TQ than in untreated diabetic rats. The histopathological results showed that treatment with TQ greatly attenuated the effect of STZ-induced diabetic nephropathy. TQ effectively adjusts glycaemic control and reduces oxidative stress in STZ-induced diabetic rats without significant damaging effects on the renal function.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules26082348
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2008644-1
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  • 9
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    Online Resource
    Effect of combined gliclazide/metformin treatment on oxidative stress, lipid profile, and hepatorenal functions in type 2 diabetic patients
    Elsevier BV ; 2018
    In:  Saudi Pharmaceutical Journal Vol. 26, No. 1 ( 2018-01), p. 1-6
    Details
    In: Saudi Pharmaceutical Journal, Elsevier BV, Vol. 26, No. 1 ( 2018-01), p. 1-6
    Type of Medium: Online Resource
    ISSN: 1319-0164
    URL: Article
    DOI: 10.1016/j.jsps.2017.11.007
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2515646-9
    SSG: 15,3
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  • 10
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    Epigenetic immunomodulatory effect of eugenol and astaxanthin on doxorubicin cytotoxicity in hormonal positive breast Cancer cells
    Springer Science and Business Media LLC ; 2021
    In:  BMC Pharmacology and Toxicology Vol. 22, No. 1 ( 2021-12)
    Details
    In: BMC Pharmacology and Toxicology, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2021-12)
    Abstract: Hormonal receptor positive (HR+) breast cancer is the most commonly diagnosed molecular subtype of breast cancer; which showed good response to doxorubicin (DOX)-based chemotherapy. Eugenol (EUG) and astaxanthin (AST) are natural compounds with proved epigenetic and immunomodulatory effects in several cancer cell lines. This study has been initiated to investigate the molecular mechanism (s) whereby EUG and AST could enhance DOX cytotoxicity in MCF7 cells. Methods Cytotoxic activity of DOX alone and combined with either 1 mM EUG or 40 μM AST was performed using sulphorhodamine-B assay in MCF7 cells. Global histones acetylation and some immunological markers were investigated using ELISA, western blotting and quantitative RT-PCR techniques. Functional assay of multidrug resistance was performed using rhodamine 123 and Hoechst 3342 dyes. Flow cytometry with annexin V and propidium iodide were used to assess the change in cell cycle and apoptosis along with the expression of some differentiation, apoptosis and autophagy proteins. Results DOX alone resulted in concentration-dependent cytotoxicity with IC 50 of 0.5 μM. Both EUG and AST significantly increased DOX cytotoxicity which is manifested as a significant decrease in DOX IC 50 from 0.5 μM to 0.088 μM with EUG and to 0.06 μM with AST. Combinations of DOX with 1 mM EUG or 40 μM AST significantly increased the level of histones acetylation and histone acetyl transferase expression, while reduced the expression of aromatase and epidermal growth factor receptor (EGFR) when compared with 0.25 μM DOX alone. Also both combinations showed higher uptake of rhodamine but lower of Hoechst stains, along with increased the percentage of caspase 3, and decreased the expression of CK7 and LC3BI/II ratio. EUG combination induced IFγ but reduced TNFα causing shifting of cells from G2/M to S and G0/ G1 phases. Combination of DOX with EUG induced apoptosis through the higher BAX/ BCl2 ratio, while with AST was through the increase in caspase 8 expressions. Conclusion EUG and AST potentiated the anticancer activity of DOX through epigenetic histones acetylation along with the immunonomodulation of different apoptotic approaches in MCF7 cells.
    Type of Medium: Online Resource
    ISSN: 2050-6511
    URL: Article
    DOI: 10.1186/s40360-021-00473-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2680259-4
    SSG: 15,3
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