RETRACTED: Tranilast ameliorated subchronic silver nanoparticles-induced cerebral toxicity in rats: Effect on TLR4/NLRP3 and Nrf-2

Fahmy, Eslam K.; El‐Sherbiny, Mohamed; Said, Eman; Elkattawy, Hany A.; Qushawy, Mona; Elsherbiny, Nehal M.

doi:10.1016/j.neuro.2020.12.008

Cited by 11 publications

(5 citation statements)

References 32 publications

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“…For instance, recent studies reported effective anti-viral activities of nanoparticles loaded with antiviral drugs, such as acyclovir fort treatment of herpes simplex virus (HSV) infection [25] and ritonavir for human immunodeficiency virus (HIV-1) [26]. Gold nano-particles (AuNps) are currently renowned for their promising therapeutic efficacies, due to their stable nature, high surface reactivity, biocompatibility, inertness, facile synthesis, and surface plasmon resonance [27,28].…”

Section: Introductionmentioning

confidence: 99%

Nanogold Particles Suppresses 5-Flurouracil-Induced Renal Injury: An Insight into the Modulation of Nrf-2 and Its Downstream Targets, HO-1 and γ-GCS

et al. 2021

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The development of the field of nanotechnology has revolutionized various aspects in the fields of modern sciences. Nano-medicine is one of the primary fields for the application of nanotechnology techniques. The current study sheds light on the reno-protective impacts of gold nano-particles; nanoGold (AuNPs) against 5-flurouracil (5-FU)-induced renal toxicity. Indeed, the use of 5-FU has been associated with kidney injury which greatly curbs its therapeutic application. In the current study, 5-FU injection was associated with a significant escalation in the indices of renal injury, i.e., creatinine and urea. Alongside this, histopathological and ultra-histopathological changes confirmed the onset of renal injury. Both gene and/or protein expression of nuclear factor erythroid 2–related factor 2 (Nrf-2) and downstream antioxidant enzymes revealed consistent paralleled anomalies. AuNPs administration induced a significant renal protection on functional, biochemical, and structural levels. Renal expression of the major sensor of the cellular oxidative status Nrf-2 escalated with a paralleled reduction in the renal expression of the other contributor to this axis, known as Kelch-like ECH-associated protein 1 (Keap-1). On the level of the effector downstream targets, heme oxygenase 1 (HO-1) and gamma-glutamylcysteine synthetase (γ-GCS) AuNPs significantly restored their gene and protein expression. Additionally, combination of AuNPs with 5-FU showed better cytotoxic effect on MCF-7 cells compared to monotreatments. Thus, it can be inferred that AuNPs conferred reno-protective impact against 5-FU with an evident modulatory impact on Nrf-2/Keap-1 and its downstream effectors, HO-1 and γ-GCS, suggesting its potential use in 5-FU regimens to improve its therapeutic outcomes and minimize its underlying nephrotoxicity.

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Section: Introductionmentioning

confidence: 99%

Nanogold Particles Suppresses 5-Flurouracil-Induced Renal Injury: An Insight into the Modulation of Nrf-2 and Its Downstream Targets, HO-1 and γ-GCS

et al. 2021

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“…Keap1 is a well-known inhibitor protein of Nrf2. Nrf2 is a key regulator of the cellular response to oxidative stress [ 44 , 45 ]. Under normal physiological conditions, Keap1 binds to Nrf2 to form a complex in a low activity state.…”

Section: Discussionmentioning

confidence: 99%

Vitamin K2 (MK-7) Intercepts Keap-1/Nrf-2/HO-1 Pathway and Hinders Inflammatory/Apoptotic Signaling and Liver Aging in Naturally Aging Rat

et al. 2022

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Aging is a naturally occurring physiological process with a deleterious impact on various body organs and humans’ well-being. The aging population is increasing worldwide, which imposes the need for the exploration of nutritional options that can intercept the impact of the aging processed on various body organs. Vitamin K2 (VK2) is a fat-soluble vitamin with emerging evidence on its therapeutic merits. In the current study, natural aging induced a significant liver deterioration with a disrupted Keap-1/Nrf-2/HO-1 axis and increased COX-2, iNOS and TNF-α expression and apoptotic and fibrotic changes. VK2 administration, on the other hand, improved the biochemical indices of liver function (total protein, albumin, ALT and AST); the suppressed hepatic expression of Keap-1 and increased the hepatic expression of Nrf-2 with a parallel increase in the hepatic activity of HO-1. Subsequently, the liver content and hepatic expression of TNF-α, COX-2 and iNOS were significantly retracted. In context, the liver content and hepatic expression of the fibrotic biomarkers TGFβ and TIMP significantly retracted as well. Moreover, the TUNEL assay confirmed the retraction of liver apoptotic changes. Of notice, electron transmission microscope examination confirmed the preservation of mitochondrial functions and preservation of the ultra-microscopical structures. In conclusion, the VK2-mediated interception of aging-induced Keap-1/Nrf-2/HO-1 signaling suppressed the hepatic contents of inflammatory and fibrotic biomarkers, as well as apoptotic changes with preservation of the hepatic architectural and functional status. VK2 can be presumed to be an effective nutritional supplement to the aging population to spare the liver, amongst other body organs, against aging-induced deleterious injury.

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“…All rats included in the study were randomly divided into four treatment groups ( n = 5/group) (Figure 1). Normal control group served as the negative control group with intravenous (iv) injection of 0.9% saline at Day 1 only and oral CMC from Day 1 to Day 7. Cis control group served as the positive control group with intravenous injection of Cis (10 mg/kg) (3), on the first day and then CMC orally until the end of the experiment. TRN100 + Cis group was injected with Cis (10 mg/kg, iv) on the first day followed by a daily oral TRN (100 mg/kg) [ 18,19 ] until Day 7. TRN300 + Cis group was injected with Cis (10 mg/kg, iv) on the first day followed by daily oral TRN (300 mg/kg) [ 17,20 ] until Day 7. …”

Section: Methodsmentioning

confidence: 99%

“…TRN300 + Cis group was injected with Cis (10 mg/kg, iv) on the first day followed by daily oral TRN (300 mg/kg) [ 17,20 ] until Day 7.…”

Section: Methodsmentioning

confidence: 99%

Tranilast abrogates cisplatin‐induced testicular and epididymal injuries: An insight into its modulatory impact on apoptosis/proliferation

Makled

Said

2021

J Biochem & Molecular Tox

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Cisplatin is a chemotherapeutic agent whose therapeutic use is greatly limited by the associated organs' toxicity and particularly, testicular toxicity. Cisplatin‐induced testicular damage reported being mediated through mitochondria‐mediated apoptosis, inflammation, and oxidative stress. Evidence showed that tranilast (TRN) has the ability to restore the oxidative status and modulate TRAIL/caspase‐8 signaling. This led us to hypothesize that TRN could abrogate cisplatin‐induced testicular and epididymal injuries via inhibiting oxidative stress and modulating proliferation and TRAIL/caspase‐8/cJNK signaling. Cisplatin injection induced oligospermia and abnormalities in testicular and epididymal structure along with impaired oxidative status. TRN administration (100 or 300 mg/kg) for 7 days post‐cisplatin injection preserved spermatogenesis and restored testicular and epididymal architecture, but restoration was more so in TRN300 than TRN100. This was in line with the restoration of balanced oxidative status as indicated by the increased total antioxidant capacity, glutathione and superoxide dismutase activity, and the decreased malondialdehyde content in testes (p < 0.05 vs. cisplatin). TRN increased the cell proliferation revealed by the increased expression of proliferating cell nuclear antigen in a dose‐dependent manner (p < 0.05 vs. cisplatin) whereas only TRN300 decreased testicular cJNK, TRAIL, and caspase‐8 expression (p < 0.05 vs. cisplatin). Moreover, TRN dose‐dependently inhibited the pro‐inflammatory transcription factor NF‐kB and the cytokine TNF‐α expressions in testes. In conclusion, TRN300 was more effective than TRN100 in alleviating cisplatin‐induced testicular and epididymal injuries and in enhancing spermatogenesis. This curative effect of TRN might be mediated through its antioxidant and anti‐inflammatory impacts along with its modulatory impact on cJNK/TRAIL/caspase‐8 signaling favoring proliferation rather than apoptosis.

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RETRACTED: Tranilast ameliorated subchronic silver nanoparticles-induced cerebral toxicity in rats: Effect on TLR4/NLRP3 and Nrf-2

Cited by 11 publications

References 32 publications

Nanogold Particles Suppresses 5-Flurouracil-Induced Renal Injury: An Insight into the Modulation of Nrf-2 and Its Downstream Targets, HO-1 and γ-GCS

Nanogold Particles Suppresses 5-Flurouracil-Induced Renal Injury: An Insight into the Modulation of Nrf-2 and Its Downstream Targets, HO-1 and γ-GCS

Vitamin K2 (MK-7) Intercepts Keap-1/Nrf-2/HO-1 Pathway and Hinders Inflammatory/Apoptotic Signaling and Liver Aging in Naturally Aging Rat

Tranilast abrogates cisplatin‐induced testicular and epididymal injuries: An insight into its modulatory impact on apoptosis/proliferation

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