Betulin alleviates cisplatin-induced hepatic injury in rats: Targeting apoptosis and Nek7-independent NLRP3 inflammasome pathways

Eisa, Nada H.; El-Sherbiny, Mohamed; El-Magd, Nada F. Abo

doi:10.1016/j.intimp.2021.107925

Cited by 9 publications

(6 citation statements)

References 49 publications

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“…In acute liver injury and hepatocyte damage induced by APAP, the NLRP3 inflammasome was significantly activated, which is consistent with previous studies 46,47 . However, the decreased expression of NEK7 in APAP-induced ALI, inhibited cleavage of pro-caspase1 and decreased levels of IL-1β upon NEK7 overexpression suggest that the activation of the NLRP3 inflammasome might not depend on NEK7 here, which is consistent with a recently reported study about acute liver injury induced by cisplatin 48 .…”

Section: Discussionsupporting

confidence: 92%

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Acetaminophen-induced reduction of NIMA-related kinase 7 expression exacerbates acute liver injury

et al. 2022

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Section: Discussionsupporting

confidence: 92%

“… 46 , 47 However, the decreased expression of NEK7 in APAP-induced ALI, inhibited cleavage of pro-caspase1 and decreased levels of IL-1β upon NEK7 overexpression suggest that the activation of the NLRP3 inflammasome might not depend on NEK7 here, which is consistent with a recently reported study about ALI induced by cisplatin. 48 …”

Section: Discussionmentioning

confidence: 99%

Acetaminophen-induced reduction of NIMA-related kinase 7 expression exacerbates acute liver injury

et al. 2022

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“…Once activated, NEK7 functions to regulate the integrity of telomeres by providing them with a protective effect from oxidative DNA damage [ 46 ]. More recently, NEK7 has been identified as a mediator of NLRP3 inflammasome activation, an innate immune response pathway that promotes inflammation and apoptosis [ 47 , 48 , 49 , 50 ]. Because of NEK7’s role in mediating the inflammasome response, it is associated with the inflammatory responses of conditions such as bacterial infections, gouty arthritis, diabetes, arterial disease, and inflammatory bowel disease [ 48 , 51 , 52 , 53 , 54 , 55 ].…”

Section: Nek7mentioning

confidence: 99%

NEK Family Review and Correlations with Patient Survival Outcomes in Various Cancer Types

Nguyen

Julia

Tran

et al. 2023

Cancers

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The Never in Mitosis Gene A (NIMA)–related kinases (NEKs) are a group of serine/threonine kinases that are involved in a wide array of cellular processes including cell cycle regulation, DNA damage repair response (DDR), apoptosis, and microtubule organization. Recent studies have identified the involvement of NEK family members in various diseases such as autoimmune disorders, malignancies, and developmental defects. Despite the existing literature exemplifying the importance of the NEK family of kinases, this family of protein kinases remains understudied. This report seeks to provide a foundation for investigating the role of different NEKs in malignancies. We do this by evaluating the 11 NEK family kinase gene expression associations with patients’ overall survival (OS) from various cancers using the Kaplan–Meier Online Tool (KMPlotter) to correlate the relationship between mRNA expression of NEK1-11 in various cancers and patient survival. Furthermore, we use the Catalog of Somatic Mutations in Cancer (COSMIC) database to identify NEK family mutations in cancers of different tissues. Overall, the data suggest that the NEK family has varying associations with patient survival in different cancers with tumor-suppressive and tumor-promoting effects being tissue-dependent.

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“…Along with CIN, cisplatin-induced liver toxicity is also associated with NLRP3 inflammasome activity, though this is far less studied. Cisplatin-treated rat liver has increased NLRP3 protein, IL-1β, and caspase 1 that is correlated with increased oxidative stress, inflammation, and liver injury [112,120]. These effects were reversed by compounds that are suggested to inhibit factors such as NF-κB and MAPK, both of which work upstream of NLRP3 and, in the case of NF-κB, are involved in priming of NLRP3 inflammasome components.…”

Section: Nod-like Receptors (Nlrs) and Inflammasomesmentioning

confidence: 99%

Pro-Inflammatory Signalling PRRopels Cisplatin-Induced Toxicity

Domingo

Latif

Bhavsar

2022

IJMS

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Cisplatin is a platinum-based chemotherapeutic that has long since been effective against a variety of solid-cancers, substantially improving the five-year survival rates for cancer patients. Its use has also historically been limited by its adverse drug reactions, or cisplatin-induced toxicities (CITs). Of these reactions, cisplatin-induced nephrotoxicity (CIN), cisplatin-induced peripheral neuropathy (CIPN), and cisplatin-induced ototoxicity (CIO) are the three most common of several CITs recognised thus far. While the anti-cancer activity of cisplatin is well understood, the mechanisms driving its toxicities have only begun to be defined. Most of the literature pertains to damage caused by oxidative stress that occurs downstream of cisplatin treatment, but recent evidence suggests that the instigator of CIT development is inflammation. Cisplatin has been shown to induce pro-inflammatory signalling in CIN, CIPN, and CIO, all of which are associated with persisting markers of inflammation, particularly from the innate immune system. This review covered the hallmarks of inflammation common and distinct between different CITs, the role of innate immune components in development of CITs, as well as current treatments targeting pro-inflammatory signalling pathways to conserve the use of cisplatin in chemotherapy and improve long-term health outcomes of cancer patients.

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Betulin alleviates cisplatin-induced hepatic injury in rats: Targeting apoptosis and Nek7-independent NLRP3 inflammasome pathways

Cited by 9 publications

References 49 publications

Acetaminophen-induced reduction of NIMA-related kinase 7 expression exacerbates acute liver injury

Acetaminophen-induced reduction of NIMA-related kinase 7 expression exacerbates acute liver injury

NEK Family Review and Correlations with Patient Survival Outcomes in Various Cancer Types

Pro-Inflammatory Signalling PRRopels Cisplatin-Induced Toxicity

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