Thymoquinone alleviates mitochondrial viability and apoptosis in diclofenac-induced acute kidney injury (AKI) via regulating Mfn2 and miR-34a mRNA expressions

Hashem, Khalid S.; Abdelazem, Ahmed Z.; Mohammed, Marwa; Nagi, Amr M; Aboulhoda, Basma Emad; Mohammed, Eman; Abdel-Daim, Mohamed M.

doi:10.1007/s11356-020-11313-x

Cited by 27 publications

(19 citation statements)

References 78 publications

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“…As an effective nephroprotective agent, ZME administration markedly alleviated DC-induced nephrotoxicity by modulating the levels of NOX4, and caspase-3. The examination of DC-treated sections using NOX4 and caspase-3 showed positive immunoreactivity with dense cytoplasmic expression in the renal tubules, which is in agreement with previous studies. , Thus, the present investigation showed that rats treated with ZME regained its normal biochemical levels and pathological changes induced by administration of DC.…”

Section: Discussionsupporting

confidence: 93%

Metabolite Profiling and Nephroprotective Potential of the Zea mays L. Silk Extract against Diclofenac-Induced Nephrotoxicity in Wistar Rats

et al. 2022

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The lack of sufficient scientific evidence prompted the analytical investigation of nephroprotective potential of the silk extract of Zea mays L., which is traditionally and ethnomedicinally used for various disorders including kidney dysfunction. The present study was conducted to investigate the phytochemical analysis and demonstrate the nephroprotective potential of the methanolic silk extract of Z. mays L. using a rodent model. High-performance thin-layer chromatography (HPTLC) analysis was carried out to standardize the methanolic silk extract of Z. mays (ZME) using naringenin as a marker. The metabolite profiling of the ZME was carried out using ultrahigh-performance liquid chromatography mass spectrometry (UPLC-MS) on a monolithic capillary silica-based C18 column to identify bioactive compounds and for confirmation of the identified markers. Furthermore, for acute toxicity study, a single dose (2000 mg/kg bw) of the ZME was administered orally to Wistar rats. Also, nephrotoxicity was induced in Wistar rats by injecting diclofenac (DC) (50 mg/kg, bw, i.p.) at a single dose. The efficacy of the ZME as a nephroprotective agent was then evaluated at doses of 100, 200, and 400 mg/kg/day, bw, p.o. Furthermore, the kidney, liver, antioxidant, inflammatory, and apoptotic biochemical markers and histopathological and immunohistochemical alterations (caspase-3 and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4 (NOX-4)) were evaluated. Phytochemical analysis by HPTLC and UPLC-MS revealed the presence of naringenin, vanillic acid, ferulic acid, gallic acid (GA), ellagic acid, quercetin, and morin, along with other bioactive constituents exhibiting multiple pharmacological properties. The acute toxicity study of the ZME showed no mortality or any clinical signs of toxicity through all the 14 days of the toxicity study at a dose of 2000 mg/kg. Also, administration of DC caused a significant elevation (P < 0.001) in kidney biochemical parameters and also caused oxidative, inflammatory, and apoptotic stress. Furthermore, DC also caused histopathological and immunohistochemical changes. Pretreatment with the ZME attenuated the elevated biochemical markers significantly at medium and high doses along with improvement in histopathological and immunohistochemical damages and showing comparable results to those of α-ketoanalogue. The present study verifies the traditional claims of Z. mays silk alleviating various kidney and related disorders by concluding the nephroprotective potential of the ZME. The nephroprotective activity of the ZME is attributed to the phytoconstituents present, acting as potent restoring antioxidants and preventing inflammatory and apoptotic cellular damages in rats. Thus, it holds promising potential in the management of nephrotoxicity.

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Section: Discussionsupporting

confidence: 93%

Metabolite Profiling and Nephroprotective Potential of the Zea mays L. Silk Extract against Diclofenac-Induced Nephrotoxicity in Wistar Rats

et al. 2022

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“…36 Similar findings have been reported linking the upregulation of renal Nrf2/HO-1 to caspase 3 downregulation by ergothioneine in cisplatin-induced nephrotoxicity, 34 by camel milk in cyclosporine-induced nephrotoxicity, 37 and by thymoquinone in diclofenacinduced acute kidney injury. 38 However, despite all previous reports, it is extremely difficult to hypothesize a cause-effect relationship between these complex pathways. 39…”

Section: Discussionmentioning

confidence: 99%

Protection of Hesperidin against Methotrexate- Induced Nephrotoxicity may be Mediated by Nrf2/HO-1 Pathway

Morsy¹,

El-Sheikh²,

Ibrahim³

et al. 2021

IJPER

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Background: Methotrexate (MTX), a successfully used chemotherapeutic in the treatment of various malignancies and autoimmune diseases, might cause severe nephrotoxicity. Here, we aimed at investigating possible nephroprotective effects of hesperidin (HES), a flavanone present in citrus fruits, against MTX-induced toxicity. Methods: Rats were divided into control, HES, MTX, and MTX/HES groups, where HES was administered in a dose of 100 mg/kg/day orally for 8 days and MTX in a single i.p. dose of 20 mg/kg on day 5 of the experiment. Results: Pretreatment with HES significantly improved MTXinduced deteriorated kidney function and structure, as well as reversed MTX effects on renal tumor necrosis factor (TNF)-α level and caspase 3 expression. MTX upregulated renal breast cancer resistance protein (BCRP); an efflux transporter that extrudes MTX from the kidney. Unfortunately, MTX/HES did not show a further increase in BCRP expression but rather showed downregulation. MTX also caused downregulation of renal nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) expressions, whereas HES reversed the MTX effect and upregulated renal Nrf2/HO-1. Conclusion: HES conferred protection against MTX-mediated nephrotoxicity, at least in part via anti-inflammatory and anti-apoptotic mechanisms. Nrf2/HO-1 pathway, but not BCRP, may have a role in HES-induced nephroprotection against MTX toxicity.

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“…TQ provide hepatorenal protection in methotrexate-induced toxicity in rats [145]. TQ possessed a potential antioxidant, antiapoptotic defense and exhibited strong nephroprotective activity against diclofenacinduced toxicity [146]. Similarly, treatment with TQ to mice also improved gentamicin-induced acute renal failure by limiting the oxidative stress [147].…”

Section: Effects Of Tq On the Urinary Systemmentioning

confidence: 99%

Occurrence and Bioactivity Diversity of Thymoquinone: An Overview

Samra

Ahmed

Shaker³

et al. 2022

Octahedron Drug Research

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Nigella sativa L. seeds are traditionally known for their ability to cure different diseases including airway and digestive system disorders, back pain, chronic headache, paralysis, diabetes, hypertension, and skin diseases. Keeping in view the numerous traditional medicinal uses of N. sativa seeds which may be related to thymoquinone (TQ), the main component of its essential oil, we provide an overview of the biological efficacy and toxicology of TQ to support their therapeutic potential in treatment of human diseases. The current review covers the recent literature from 2002 to 2021. The data was collected from books, journals, electronic searches (Pub Med, ScienceDirect, Google Scholar, and Springerlink), and theses. Thymoquinone exhibits importance in combating various diseases such as inflammation, arthritis, ulcerative colitis, cancer. Also, it showed ability to cure neuropathic pain, male infertility, diabetes, hepatitis, cardiovascular, musculoskeletal, respiratory, renal, skin, microbial infection, and neurodegenerative diseases comprising Parkinson's and Alzheimer's. That explains the traditional uses of N. sativa seeds in folk remedies in curing different ailments. The current review provides an explanation of the ethnopharmacological uses of N. sativa L. seeds which are related to the pharmacological activities of TQ. The pharmacological properties, pharmacokinetics, efficacy, high therapeutic index, lipophilicity, and safety margin make TQ a hopeful candidate for drug development.

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Thymoquinone alleviates mitochondrial viability and apoptosis in diclofenac-induced acute kidney injury (AKI) via regulating Mfn2 and miR-34a mRNA expressions

Cited by 27 publications

References 78 publications

Metabolite Profiling and Nephroprotective Potential of the Zea mays L. Silk Extract against Diclofenac-Induced Nephrotoxicity in Wistar Rats

Metabolite Profiling and Nephroprotective Potential of the Zea mays L. Silk Extract against Diclofenac-Induced Nephrotoxicity in Wistar Rats

Protection of Hesperidin against Methotrexate- Induced Nephrotoxicity may be Mediated by Nrf2/HO-1 Pathway

Occurrence and Bioactivity Diversity of Thymoquinone: An Overview

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