Umbelliferone attenuates gentamicin-induced renal toxicity by suppression of TLR-4/NF-κB-p65/NLRP-3 and JAK1/STAT-3 signaling pathways

Hassanein, Emad H.M.; Ali, Fares E.M.; Kozman, Magy R.; El-Ghafar, Omnia A M Abd

doi:10.1007/s11356-020-11416-5

Cited by 36 publications

(14 citation statements)

References 63 publications

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“…At the beginning (initial body weight) and at the time of sacrificing (final total body weight), body weight was assessed. The renal somatic index (RSI) was determined using the method described previously (Hassanein et al., 2020). Briefly, kidneys were isolated and washed with PBS, dried, and weighed.…”

Section: Methodsmentioning

confidence: 99%

Diallyl disulfide ameliorates methotrexate‐induced nephropathy in rats: Molecular studies and network pharmacology analysis

et al. 2021

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Methotrexate (MTX) is a promising chemotherapeutic agent. Its medical use is limited by induced nephropathy. Our study was designed to explore the reno‐protective effect of diallyl disulfide (DADS), an organosulfur compound of garlic oil, on MTX‐induced nephropathy. Adult rats were randomly divided into 4 groups; normal control, DADS (50 mg kg–1 day–1, p.o.), MTX (20 mg/kg, i.p.) and DADS+MTX. DADS significantly decreased serum creatinine, urea, uric acid, and albumin levels with an improvement of final body weight. Additionally, DADS markedly attenuated MTX‐induced elevations in renal MDA and NO2‐ contents with an increase in GSH content and SOD activity. Mechanistically, DADS effectively down‐regulated mRNA expression level of renal p38 and NF‐κB. Additionally, DADS positively regulated the NRF2 gene with a remarkable inhibition of Keap‐1 gene. Furthermore, DADS up‐regulated BCL2 protein and remarkably suppressed the expression of both BAX and caspase‐3 proteins. Overall, DADS has favorable renal protection against MTX‐induced nephropathy via modulation of Keap‐1/NRF2, p38/NF‐κB, and BCL2/BAX/caspase‐3 signaling. Practical applications Diallyl disulfide is one of the organosulfur compounds of garlic oil. Our study demonstrated that DADS substantially alleviated the decline of kidney function and renal injury induced by MTX. The antioxidative, anti‐inﬂammatory, and anti‐apoptotic properties may constitute an important part of its therapeutic applications via regulation of p38/NF‐κB, Keap‐1/NRF2, and BCL2/BAX/caspase‐3 signaling pathways. Therefore, DADS could be a potential therapeutic adjunct in cancer chemotherapy to decrease the associated side effects of MTX. It should be further explored clinically as a protective agent for MTX‐treated cancer patients.

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Section: Methodsmentioning

confidence: 99%

Diallyl disulfide ameliorates methotrexate‐induced nephropathy in rats: Molecular studies and network pharmacology analysis

et al. 2021

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“…There are fewer data about the involvement of TLR4 in this type of AKI. However, two recent studies described that pretreatment with pirfenidone or umbelliferone caused a reduction in renal damage through the inhibition of the TLR4/NFκB/NLRP-3 pathway in an experimental model of gentamicin-induced AKI [171,172].…”

Section: Exogenous Toxicitymentioning

confidence: 99%

Toll-Like Receptors in Acute Kidney Injury

Vázquez‐Carballo

Guerrero‐Hue

García‐Caballero

et al. 2021

IJMS

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Acute kidney injury (AKI) is an important health problem, affecting 13.3 million individuals/year. It is associated with increased mortality, mainly in low- and middle-income countries, where renal replacement therapy is limited. Moreover, survivors show adverse long-term outcomes, including increased risk of developing recurrent AKI bouts, cardiovascular events, and chronic kidney disease. However, there are no specific treatments to decrease the adverse consequences of AKI. Epidemiological and preclinical studies show the pathological role of inflammation in AKI, not only at the acute phase but also in the progression to chronic kidney disease. Toll-like receptors (TLRs) are key regulators of the inflammatory response and have been associated to many cellular processes activated during AKI. For that reason, a number of anti-inflammatory agents targeting TLRs have been analyzed in preclinical studies to decrease renal damage during AKI. In this review, we updated recent knowledge about the role of TLRs, mainly TLR4, in the initiation and development of AKI as well as novel compounds targeting these molecules to diminish kidney injury associated to this pathological condition.

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“…The activated NF-κB (p65) as a downstream protein of PEDF plays an important role in various diseases (Ren et al, 2017;Zhou et al, 2013;Zhu et al, 2012). Studies (Ali et al, 2020;Hassanein et al, 2021) have shown that Caspases, especially Caspase-3, are regulated by NF-κB (p65) and plays a key role in execution of apoptosis. When apoptosis occurs, after being stimulated by the apoptotic signals, the effector Caspases are crucial to the progress of the apoptotic program, but the activation of this process requires the initiator Caspases to cut their precursors.…”

Section: Discussionmentioning

confidence: 99%

DHA-promoted repair of human corneal epithelial cells in high-glucose environment

et al. 2022

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Materials and methods MaterialsCorneal epithelial progenitor cells (TKE2) (ATCC); highglucose DMEM (Giboco); trypsin 0.25% (NanJing KeyGen Biotech); flow cytometry kit (NanJing KeyGen Biotech); Hoechst 33258 staining solution (Beyotime Institute of Biotechnology); PEDF, VEGF, Caspase-3, Caspase-9, and p-NF-κB (p65) antibodies (Abcam); PEDF, VEGF, Caspase-3, Caspase-9, and NF-κB (p65) primer sequence (NanJing KeyGen Biotech). Cell cultureAfter resuscitation, TKE2 cells were resuspended in complete medium (high-glucose DMEM+10% FBS) and placed in an incubator with 5% carbon dioxide at 37 °C. When the cells had grown to more than 80% adherently, subculture was conducted: The cells in the logarithmic growth phase were digested to prepare a single cell suspension, which was then inoculated in the culture plate at 1×104 / well and cultured in a cell incubator with 0.5% CO2 at 37 °C. After the cells were subcultured for one to two passages, they were subcultured to a total of 10 culture dishes of 35mm in diameter following the above method. The human corneal epithelial cells were stimulated with highglucose concentration (25 mmol/ L glucose in DMEM complete medium) to establish the Model group.

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Umbelliferone attenuates gentamicin-induced renal toxicity by suppression of TLR-4/NF-κB-p65/NLRP-3 and JAK1/STAT-3 signaling pathways

Cited by 36 publications

References 63 publications

Diallyl disulfide ameliorates methotrexate‐induced nephropathy in rats: Molecular studies and network pharmacology analysis

Diallyl disulfide ameliorates methotrexate‐induced nephropathy in rats: Molecular studies and network pharmacology analysis

Toll-Like Receptors in Acute Kidney Injury

DHA-promoted repair of human corneal epithelial cells in high-glucose environment

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