Alleviation of prilocaine-induced epileptiform activity and cardiotoxicity by thymoquinone

Akgül, Barış; Aycan, İlker Öngüç; Hidişoğlu, Enis; Afşar, Ebru; Yıldırım, Sendegül; Tanrıöver, Gamze; Coşkunfırat, Nesil; Sanlı, Suat; Aslan, Mutay

doi:10.1007/s40199-020-00385-2

Cited by 13 publications

(11 citation statements)

References 51 publications

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“…Thymoquinone (TQ) (2‐isopropyl‐5‐methyl‐1,4‐benzoquinone) (Figure 1) is a natural product derived from black cumin Nigella sativa . [ 6 ] TQ has been documented for pharmacological effects such as anti‐inflammatory, [ 7 ] antioxidant, [ 8 ] cardioprotective, [ 9 ] hepatoprotective, [ 10 ] neuroprotective, [ 11 ] antidiabetic, [ 12 ] anti‐depressant, [ 13 ] and fungicidal activities. [ 14 ] The anticancer effect of TQ has been reported in different types of cancers including prostate cancer, osteosarcoma, fibrosarcoma, myeloblastic leukemia, colorectal carcinoma, and lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant, antiproliferative, and apoptotic activity of thymoquinone against benzo(a)pyrene‐induced experimental lung cancer

Nithya

Rajasekaran

Vanitha

et al. 2022

J Biochem & Molecular Tox

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Several studies have suggested that increased consumption of phytochemicals is a comparatively easy and practical strategy to significantly decrease the incidence of cancer. In the present study, we have reported the protective effect of a natural compound, thymoquinone (TQ) against benzo(a)pyrene (B(a)P)‐induced lung carcinogenesis in Swiss albino mice. B(a)P (50 mg/kg body weight) was administered twice weekly for four successive weeks and left until 20 weeks to induce lung cancer in mice. TQ (20 mg/kg body weight) was given orally as a pretreatment and posttreatment drug to determine its chemopreventive and therapeutic effects. B(a)P‐induced lung cancer‐bearing animals displayed cachexia‐like symptoms along with an abnormal increase in lung weight and the activities of marker enzymes adenosine deaminase, aryl hydrocarbon hydroxylase, gamma‐glutamyl transpeptidase, 5′‐nucleotidase and lactate dehydrogenase; tumor marker carcinoembryonic antigen levels. Furthermore, B(a)P‐induced animals showed elevated levels of lipid peroxides with subsequent depletion in the antioxidant status and histological aberrations. These anomalies were accompanied by increased expressions of proliferating cell nuclear antigen and cyclin D1 in the lung sections derived from B(a)P‐induced animals. On TQ treatment, all the above alterations were returned to near normalcy. Furthermore, TQ administration in B(a)P‐induced animals downregulated phosphatidylinositol 3‐kinase/protein kinase B signaling pathway and induced apoptosis as evidenced by a decrease in cytochrome c, proapoptotic Bax, caspase‐3, and p53 with a parallel increase in antiapoptotic Bcl‐2. Our present results demonstrate the potential effectiveness of TQ as an antioxidant, antiproliferative, and apoptotic agent against B(a)P‐induced experimental lung tumorigenesis.

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Section: Introductionmentioning

confidence: 99%

Antioxidant, antiproliferative, and apoptotic activity of thymoquinone against benzo(a)pyrene‐induced experimental lung cancer

Nithya

Rajasekaran

Vanitha

et al. 2022

J Biochem & Molecular Tox

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“…[ 17 ] We recently observed an increased expression of the central nervous system NFκB‐p65 and NFκB‐p50 in a rat model for PRL toxicity. [ 18 ] As previously reported, the NFκB‐p65 inflammatory pathway increases the expression of inducible nitric oxide synthase (iNOS; NOS2) enzyme. [ 19 ]…”

Section: Introductionmentioning

confidence: 80%

“…Activation of TLRs also activates the NF‐κB pathway [ 39 ] and we recently showed increased central nervous system NFκB‐p65 and NFκB‐p50 expressions in a rat model for PRL toxicity. [ 18 ] For this reason, we measured the levels of NF‐κB p65 and phosphorylated NF‐κB P65 (Ser 536) in our experimental cell model (Figure 2). There are five members of NF‐κB transcription factors in mammals, among them p65 and p50 are the most abundant in the cell.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory signal transduction pathways induced by prilocaine toxicity in cultured ARPE‐19 cells

Öztüzün

Çeker

Yılmaz

et al. 2023

J Biochem & Molecular Tox

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Prilocaine (PRL) is a common local anesthetic. Despite the successful use of regional anesthesia for intraocular surgery, there are associated side effects that may affect the retina in case of accidental intravitreal injection. This study examined the signal transduction pathways activated by PRL toxicity and determined the protective role of nitric oxide synthase‐2 (NOS2) inhibition in cultured human‐derived retinal pigment epithelial cells (ARPE‐19). Toxicity analysis was performed using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay to detect the toxic dose of PRL and protective effectiveness of asperglaucide (ASP), an NOS2 inhibitor. Nuclear factor kappa B p65 (NF‐κB p65), phosphorylated NF‐κB p65, phospho‐protein kinase B (AKT), NOS2, nitrotyrosine, and cleaved caspase‐3 protein levels were evaluated by immunofluorescence staining and/or western blot analysis. Interleukin‐6 (IL‐6) and nitrated protein levels were quantified using an immunoassay, whereas caspase‐3 activity and nitrite/nitrate levels were measured using a fluorometric method. A significant increase in NF‐κB p65, and phosphorylated NF‐κB p65 and AKT levels due to PRL toxicity was observed. Similarly, IL‐6, NOS2, nitrite/nitrate, and nitrotyrosine levels were significantly higher in PRL‐treated cells than in control cells. Application of ASP to PRL‐treated cells reduced NF‐κB p65, and phosphorylated NF‐κB p65 and AKT to basal levels. IL‐6, NOS2, nitrite/nitrate, and nitrotyrosine levels also considerably decreased following ASP treatment in cells experiencing PRL‐induced toxicity. Moreover, the caspase‐3‐dependent apoptotic pathway was not activated. Our results indicate that ASP could ameliorate PRL‐induced activation of NF‐κB p65 that led to inflammation in cultured ARPE‐19 cells.

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“…Concerning the vital roles of TQ, several investigations have explored the development of TQ analog compounds with notable efficacy for different types of diseases ( Goyal et al, 2017 ). Previous studies explained that TQ induces an antioxidant, anti-inflammatory, anti-apoptotic and immunomodulatory effects ( Aycan et al, 2014 , Shaterzadeh-Yazdi et al, 2018 , Abdel-Daim et al, 2019 , Guo et al, 2020 , Akgül et al, 2021 , Landucci et al, 2021 , Khalifa et al, 2021 ). Al Aboud et al (2021) investigated the hepato-protective influence of TQ in rats exposed to arsenic (As).…”

Section: Discussionmentioning

confidence: 97%

Hematological and biochemical investigations on the effect of curcumin and Thymoquinone in male mice exposed to Thioacetamide

Al-Attar

2022

Saudi Journal of Biological Sciences

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Currently, living organisms are increasingly exposed to many toxic chemicals in the environment. These substances pose a threat to human life, other living organisms and ecosystem. In fact, there is an increasing requirement to search for safe therapeutic sources today. Medicinal plants and natural products have become of great importance globally because of their therapeutic potential and medicinal properties, as well as their availability and the absence of harmful side effects for most of them. The present study was designed to explore the potential protective effect of curcumin (CUR) and thymoquinone (TQ) in male rats exposed to thioacetamide (TAA). The experimental mice were divided into eight groups. Group 1 was served as control. Group 2 was exposed to 50 mg/ kg body weight of TAA. Group 3 was exposed to CUR and TAA. Mice of group 4 were treated with TQ and TAA. Mice of group 5 were exposed to CUR plus TQ and TAA. Group 6 was supplemented with CUR. Group 7 was subjected to TQ. Mice of group 8 were treated with CUR and TQ. Hematological and biochemical alterations were evaluated after one month. Significant increases of white blood corpuscles (WBC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) values were observed in group 2, while the values of red blood corpuscles (RBC), hemoglobin (Hb(, hematocrit (Hct), glutathione (GSH) and superoxide dismutase (SOD) were statistically decreased. Treatment with CUR, TQ and their combination inhibited the hematological and biochemical alterations induced by TAA toxicity. Moreover, the most protective effect was observed in mice treated with CUR plus TQ. These new results suggested that the protective effect of CUR and TQ attributed to their antioxidant properties.

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Alleviation of prilocaine-induced epileptiform activity and cardiotoxicity by thymoquinone

Cited by 13 publications

References 51 publications

Antioxidant, antiproliferative, and apoptotic activity of thymoquinone against benzo(a)pyrene‐induced experimental lung cancer

Antioxidant, antiproliferative, and apoptotic activity of thymoquinone against benzo(a)pyrene‐induced experimental lung cancer

Inflammatory signal transduction pathways induced by prilocaine toxicity in cultured ARPE‐19 cells

Hematological and biochemical investigations on the effect of curcumin and Thymoquinone in male mice exposed to Thioacetamide

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