Ajwa dates (Phoenix dactylifera L.) attenuate cisplatin-induced nephrotoxicity in rats via augmenting Nrf2, modulating NADPH oxidase-4 and mitigating inflammatory/apoptotic mediators

Abdelghffar, Eman A.; Obaid, Wael A.; Saleh, Zuhair M. Mohammed; Ouchari, Wafae; Eldahshan, Omayma A.; Sobeh, Mansour

doi:10.1016/j.biopha.2022.113836

Cited by 11 publications

(7 citation statements)

References 43 publications

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“…Conversely, E. alata treatment at a dose of 40 mg/kg significantly attenuated the observed genotoxicity and decreased the alteration of the DNA profile induced by acephate exposure. Several mechanisms could explain this effect, some of which were linked to the presence of a high level of beneficial metabolites known for their inhibitor properties of DNA fragmentation in renal tissue, as reported by previous studies [47,48].…”

Section: Discussionmentioning

confidence: 73%

Ephedra alata Seeds Confer Kidney Protection against Early Life Exposure to Acephate by Regulating Oxidative Insult and Activating Autophagy

Mufti,

Feriani,

Contreras

et al. 2023

Life

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The aim of the current work was to examine for the first time the nephropreventive capacity of Ephedra alata seed extract (E) against maternal exposure to acephate in rat offspring. The in vivo results revealed that E. alata supplementation for 28 days (40 mg/kg b.w.) significantly attenuated the nephrotoxicity in adult offspring induced by acephate. In fact, it decreased the levels of creatinine and uric acid and increased the albumin content compared to the intoxicated group. The in utero studies showed that E. alata inhibited the renal oxidative stress generated by acephate exposure by reducing lipid peroxidation and enhancing antioxidant biomarker activities (GSH, CAT, and SOD). The inhibition of DNA fragmentation and the improvement of the ultrastructural changes highlighted the prophylactic effect of E. alata in renal tissue. Additionally, the immunofluorescence study showed the upregulation of LC3 gene expression, suggesting the capacity of E. alata extract to stimulate autophagic processes as a protective mechanism. Molecular docking analysis indicated that hexadecasphinganine, the major compound in E. alata, has a higher affinity toward the Na+/K+-ATPase, epithelial sodium channel (ENaC), and sodium hydrogen exchanger 3 (NHE3) genes than acephate. Hexadecasphinganine could be considered a potential inhibitor of the activity of these genes and therefore exerted its preventive capacity. The obtained findings confirmed that E. alata seed extract exerted nephropreventive capacities, which could be related to its bioactive compounds, which possess antioxidant activities.

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Section: Discussionmentioning

confidence: 73%

Ephedra alata Seeds Confer Kidney Protection against Early Life Exposure to Acephate by Regulating Oxidative Insult and Activating Autophagy

Mufti,

Feriani,

Contreras

et al. 2023

Life

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“…A previous study assessed the effect of date palm seeds’ dietary supplementation on broilers’ growth and carcass performances and revealed that date palm seeds exhibited escalations in IFN-γ, signifying the immune-stimulant constituents of the seeds [ 63 ]. Date palm fruit extract has exhibited anti-inflammatory actions in several hepatic models, such as mercury [ 13 ] or cisplatin [ 11 ] induced hepatic injury, and in non-hepatic models, such as isoproterenol-induced cardiomyopathy [ 64 ] and cisplatin-induced nephrotoxicity [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

The Hepatoprotective Effect of Two Date Palm Fruit Cultivars’ Extracts: Green Optimization of the Extraction Process

Alqahtani

Mohamed

Moawad

et al. 2023

Foods

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Date palm fruit (Phoenix dactylifera: Arecaceae) is rich in essential nutrients and possesses several pharmacological and medicinal activities. The current study aimed to optimize a water bath-assisted extraction method for two cultivars of date palm fruits, Anbara (An) and Reziz (Rz), and investigated the protective effect of the optimized date palm fruit extract against CCl4-induced liver toxicity in relation to oxidative stress, inflammation, apoptosis, and DNA integrity. The optimization process of two date palm fruit cultivars was applied, using response surface methodology through adjusting three “factors”; time, temperature, and rotation, to allow maximum contents of total phenolic (TPC), total flavonoid (TFC), reducing power (FRAP) and scavenging activity (ABTS) of the extract “responses”. Extraction factors’ application significantly enhanced TPC, TFC, FRAP, and ABTS responses by 1.30, 1.23, 3.03, and 2.06-fold, respectively in An and 2.18, 1.71, 1.11, and 2.62-fold, respectively in Rz, in relation to the convectional water extraction. Furthermore, co-administered CCl4 with An or Rz optimized extracts enhanced body weight gain, amended hepatic architecture, and diminished collagen fiber accumulation. Furthermore, An or Rz extracts reduced liver enzymes, hydroxyproline, alpha-fetoprotein (AFP), MDA, inflammatory cytokine (TNF-α, NF-κB) levels, and DNA fragmentation, while increasing deteriorated adiponectin (ADP) and antioxidant enzyme (GSH, GPX, NO, and IFN-γ) levels, relative to CCl4-administered animals. The protective effects of An or Rz-optimized extracts were also evidenced by suppressing hepatic fibrosis and improving liver function and structure via modulating oxidative stress, inflammation, and apoptosis, in CCl4-induced hepatic damage. Hence, the optimized extraction process for the two date palm fruits resulted in extracts which are rich in phenolic and flavonoid contents and with an elevated antioxidant power. The presence of these rich extracts could help to explain their proven hepatoprotective activity against CCl4-induced liver toxicity.

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“…[230][231][232][233] Indeed, resveratrol, a plant polyphenol, activates Nrf2 and inhibits the KEAP1 pathway, improving the antiinflammatory and antioxidant properties of the Nrf2 signaling pathway. [234] Also, resveratrol augments endogenous antioxidant capacity independent of the Nrf2 signaling pathway. [234] In vitro study demonstrated that resveratrol inhibits ROS production by activating the Nrf2 pathway and inhibiting Keap1 pathway a negative regulator of Nrf2.…”

Section: Resveratrolmentioning

confidence: 99%

“…[ 234 ] Also, resveratrol augments endogenous antioxidant capacity independent of the Nrf2 signaling pathway. [ 234 ] In vitro study demonstrated that resveratrol inhibits ROS production by activating the Nrf2 pathway and inhibiting Keap1 pathway a negative regulator of Nrf2. [ 231 ] Resveratrol also acts as an antiviral agent through different mechanisms of action.…”

Section: Nrf2 In Covid‐19mentioning

confidence: 99%

The possible role of nuclear factor erythroid‐2‐related factor 2 activators in the management of Covid‐19

Al‐kuraishy,

Al‐Gareeb,

Eldahshan

et al. 2023

J Biochem & Molecular Tox

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COVID‐19 is caused by a novel SARS‐CoV‐2 leading to pulmonary and extra‐pulmonary manifestations due to oxidative stress (OS) development and hyperinflammation. COVID‐19 is primarily asymptomatic though it may cause acute lung injury (ALI), acute respiratory distress syndrome (ARDS), systemic inflammation, and thrombotic events in severe cases. SARS‐CoV‐2‐induced OS triggers the activation of different signaling pathways, which counterbalances this complication. One of these pathways is nuclear factor erythroid 2‐related factor 2 (Nrf2), which induces a series of cellular interactions to mitigate SARS‐CoV‐2‐mediated viral toxicity and OS‐induced cellular injury. Nrf2 pathway inhibits the expression of pro‐inflammatory cytokines and the development of cytokine storm in COVID‐19. Therefore, Nrf2 activators may play an essential role in reducing SARS‐CoV‐2 infection‐induced inflammation by suppressing NLRP3 inflammasome in COVID‐19. Furthermore, Nrf2 activators can attenuate endothelial dysfunction (ED), renin‐angiotensin system (RAS) dysregulation, immune thrombosis, and coagulopathy. Thus this mini‐review tries to clarify the possible role of the Nrf2 activators in the management of COVID‐19. Nrf2 activators could be an effective therapeutic strategy in the management of Covid‐19. Preclinical and clinical studies are recommended in this regard.

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Ajwa dates (Phoenix dactylifera L.) attenuate cisplatin-induced nephrotoxicity in rats via augmenting Nrf2, modulating NADPH oxidase-4 and mitigating inflammatory/apoptotic mediators

Cited by 11 publications

References 43 publications

Ephedra alata Seeds Confer Kidney Protection against Early Life Exposure to Acephate by Regulating Oxidative Insult and Activating Autophagy

Ephedra alata Seeds Confer Kidney Protection against Early Life Exposure to Acephate by Regulating Oxidative Insult and Activating Autophagy

The Hepatoprotective Effect of Two Date Palm Fruit Cultivars’ Extracts: Green Optimization of the Extraction Process

The possible role of nuclear factor erythroid‐2‐related factor 2 activators in the management of Covid‐19

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