Phyto-sesquiterpene lactone deoxyelephantopin and cisplatin synergistically suppress lung metastasis of B16 melanoma in mice with reduced nephrotoxicity
24
Citation
39
Reference
10
Related Paper
Citation Trend
Keywords:
Nephrotoxicity
Sesquiterpene lactone
Nephrotoxicity
Rhodamine 123
Cite
Citations (66)
Cisplatin is one of the most widely used and highly effective drug for the treatment of various solid tumors; however, it has dose-dependent side effects on the kidney, cochlear, and nerves.Nephrotoxicity is the most well-known and clinically important toxicity.Numerous studies have demonstrated that several mechanisms, including oxidative stress, DNA damage, and inflammatory responses, are closely associated with cisplatin-induced nephrotoxicity.Even though the establishment of cisplatin-induced nephrotoxicity can be alleviated by diuretics and pre-hydration of patients, the prevalence of cisplatin nephrotoxicity is still high, occurring in approximately one-third of patients who have undergone cisplatin therapy.Therefore it is imperative to develop treatments that will ameliorate cisplatin-nephrotoxicity.In this review, we discuss the mechanisms of cisplatin-induced renal toxicity and the new strategies for protecting the kidneys from the toxic effects without lowering the tumoricidal activity.
Nephrotoxicity
Ototoxicity
Cite
Citations (198)
Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Despite intensive research, the mechanism of cisplatin-induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin-based chemotherapy are lacking. Here we have identified PKCδ as a critical regulator of cisplatin nephrotoxicity, which can be effectively targeted for renoprotection during chemotherapy. We showed that early during cisplatin nephrotoxicity, Src interacted with, phosphorylated, and activated PKCδ in mouse kidney lysates. After activation, PKCδ regulated MAPKs, but not p53, to induce renal cell apoptosis. Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. Conversely, inhibition of PKCδ enhanced cisplatin-induced cell death in multiple cancer cell lines and, remarkably, enhanced the chemotherapeutic effects of cisplatin in several xenograft and syngeneic mouse tumor models while protecting kidneys from nephrotoxicity. Together these results demonstrate a role of PKCδ in cisplatin nephrotoxicity and support targeting PKCδ as an effective strategy for renoprotection during cisplatin-based cancer therapy.
Nephrotoxicity
Cite
Citations (137)
A molecular analysis of cross‐reactions in costus‐sensitive patients reveals that the most active sesquiterpene lactones are the ones with the lesser number of oxygenated substiuents dose to the α‐methylene γ‐butyrolactone ring. Cross‐reactions with sesquiterpene lactones with different skeletons (germacranolide and guaianolide or pseudoguaianolide lactones) can probably be explained by concomitant multiple sensitization to two lactones present in costus. respectively costunolide and dehydrocostus lactone.
Germacranolide
Sesquiterpene lactone
Cite
Citations (18)
Abstract Vlasouliolides A-D ( 1 – 4 ), four rare sesquiterpene lactone dimers, were isolated from Vladimiria souliei . The common structural characteristic of 1 – 4 is the C 32 skeleton comprising two sesquiterpene lactone units linked by a C11-C13′ single bond with one acetyl connected to the C-13 position of one of the two sesquiterpene lactone units. The stereochemistries of 1 – 4 were assigned by a combination of NOESY correlations and Cu-Κ α X-ray crystallographic analyses. Compounds 1 – 4 strongly inhibited the production of NO in LPS-stimulated RAW 264.7 cells. Furthermore, 1 and 2 inhibited the activation of NF- κ B in LPS-induced 293T cells.
Sesquiterpene lactone
Cite
Citations (20)
Nephrotoxicity
Moiety
Cite
Citations (242)
Sesquiterpene lactone
Inula
Cite
Citations (27)
Animal experiment and clinical observation were carried out to study the nephrotoxicity of cisplatin in order to give protective measures. In animal experiment it had been demonstrated that the nephrotoxicity induced by cisplatin was mainly related to the intraperitoneal concentration of cisplatin. The nephrotoxicity was permanent in rats treated with cumulative cisplatin. The main pathologic lesions were characterized by interstitial hyperemia, degeneration of the tubular cells and formation of tubular casts. In a Clinical study to compare two preventive methods (sodium thiosulfate and hydration) from cisplatin induced nephrotoxicity, the BUN and serum Cr were measured in 28 patients. The results revealed that there was no significant difference between the two groups (P greater than 0.05). The two protective measures had similar effect in reducing the nephrotoxicity of cisplatin. Five of 6 patients treated with cisplatin developed hypo-magnesemia but only one had symptoms.
Nephrotoxicity
Sodium thiosulfate
Intraperitoneal injection
Cite
Citations (1)
Cisplatin, a widely-used chemotherapeutic agent for treating many human malignancies. The mechanism of cisplatin, which disrupts cellular DNA and induces cell apoptosis, can effectively cease the spread of cancerous cells and damage normal cells. Hence, many side effects are related to cisplatin-based treatments. Nephrotoxicity, the toxicity it has on kidneys, is a significant side effect of cisplatin. Although doses of cisplatin are carefully examined before giving to the patients, many still experience kidney injuries and insufficiencies to a different extent. Cisplatin not only accumulates in mitochondria and cells in our kidneys, but its highly reactive thiol metabolites can induce even more injury to our body as it is more toxic than cisplatin itself. Human bodies resist cisplatin with inflammatory response and regulation of cytokines, transporter proteins, hormones, and the expression of genes and transcription factors. However, medical treatments that involve Amifostine and saline solution are still used to facilitate the recovery of patients with nephrotoxicity. This article provides a general view of the latest advancement in our understanding of cisplatin, cisplatin nephrotoxicity, and the future outlook on unsolved problems regarding cisplatin nephrotoxicity.
Nephrotoxicity
Amifostine
Cite
Citations (0)