Oct 15, 2019 cisplatin induced nephrotoxicity can be manifested as acute kidney injury aki, or as different types of tubulopathies, salt wasting, loss of urinary concentrating ability, and magnesium wasting. Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. An extract of rhodobacter sphaeroides reduces cisplatin. For revealing the dose and timedependence of cisplatin induced nephrotoxicity, mass spectrometrybased metabolomics integrated with a principal componentbased area calculation pcac strategy was proposed in the present study. Discovery of potential biomarkers with dose and time. Although cisplatininduced chronic kidney disease ckd in rodent has been reported, the role of. The first occurrence of nephrotoxicity was documented in the. The renoprotective effect of curcumin in cisplatin induced nephrotoxicity. The attenuation of cisplatin caused aki is currently accomplished by hydration, magnesium supplementation or mannitol induced forced diuresis.
Cisplatin cpinduced nephrotoxicity is widely accepted as a model for acute kidney injury aki. New insights in the pathogenesis of cisplatininduced. Although cisplatin induced chronic kidney disease ckd in rodent has been reported, the role of. Recent studies have improved our understanding of the molecular mechanisms of cisplatininduced nephrotoxicity and ototoxicity. Cisplatin is a platinum containing drug first approved as an antineoplastic agent in 1978. Myeloma cast nephropathy is an obstructing disorder of renal tubules, caused by precipitation of bence jones proteins. Protective effect of rutin supplementation against. Renal cell apoptosis, oxidative stress, and inflammation contribute to cisplatininduced nephrotoxicity. Hepatotoxicity and nephrotoxicity are important drawbacks of cisplatin.
The effects of cisplatininduced nephrotoxicity on the pharmacokinetics of a renally excreted antibiotic, gentamicin, were studied in f344 rats. Despite intensive research, the mechanism of cisplatin induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin based chemotherapy are lacking. Recent research has shed significant new lights on the mechanism of cisplatin nephrotoxicity, especially on the signaling pathways leading to tubular cell death. The present study was performed to explore the effect of curcumin against cisplatin. We aimed to investigate the renoprotective effects of dendropanax morbifera water extract dm on cddp induced aki. Cisplatininduced nephrotoxicity and targets of nephroprotection. Previously, we found that an extract of rhodobacter sphaeroides lycogen inhibited proinflammatory cytokines and the production of nitric oxide in activated macrophages in a dextran sodium sulfate dssinduced colitis model. Therefore, the present study aimed to study the possible protective effect of rutin against nephrotoxicity induced by cisplatin in rats. Risk factors for cisplatininduced nephrotoxicity and. Cytotoxicity of cisplatin there is convincing evidence that the primary biochemical lesion induced by cisplatin in cancer cells is. Cisplatin cp is commonly used in the treatment of different types of cancer but nephrotoxicity has been a major limiting factor. Nephrotoxicity is a major complication and a dose limiting factor for cisplatin therapy. A single dose of gentamicin 30 mgkg, iv was given to different groups of rats alone, at the same time as, or on day 4, 7, 15, or 29 following cisplatin administration 6 mgkg, iv. Cisplatin nephrotoxicity is clearly doserelated and used to be considered dose limiting.
Cisplatin dose rate as a risk factor for nephrotoxicity in. It remains an important and effective therapy in many forms of cancer today. Forty male wistar albino rats were randomly divided into 4 groups. Jun 15, 2017 cisplatin cp is commonly used in the treatment of different types of cancer but nephrotoxicity has been a major limiting factor. However, its clinical use is severely limited by serious sideeffects, of which nephrotoxicity and myelosuppression are considered to be the most important because they significantly reduce patient life quality and hinder effective use. Dhapc protects kidneys against cisplatininduced toxicity. An integrated view of cisplatininduced nephrotoxicity and. Ambroxol attenuates cisplatininduced hepatotoxicity and. Various regimens have been developed to treat cancer based on the type and severity of the tumor.
In the curative regimen, the ethanolic extract at dose levels of 250 and 500 mgkg showed dosedependent reduction in the elevated blood urea and serum creatinine. The authors give a comprehensive overview of the molecular mechanisms of cisplatininduced toxicity in the kidney and also present the. Cisplatin and related platinumbased therapeutics are now being used for. However, the optimal strategy for preventing cisplatin. Patients at highest risk of drug induced nephrotoxicity are those with one or more of the following. Nephrotoxicity due to a aminoglycosides b cyclophosphamide c cisplatin d radiocontrast e analgesic f amphotericin g crystal.
There was increase in the gsh and gst enzyme level after treating rats with. Cisplatininduced nephrotoxicity can be manifested as acute kidney injury aki, or as different types of tubulopathies, salt wasting, loss of urinary concentrating ability, and magnesium wasting. Cisplatininduced renal toxicity and toxicitymodulating strategies. Nephrotoxicity is a wellknown side effect of cisplatin for cancer treatment. Inflammatory, oxidative stress, and apoptotic biomarkers were. This study aims to explore whether sac protects against cp. Cisplatin is one of the most widelyused drugs to treat cancers. Cisplatin mediates its tumorcidal effects via a number of different cytotoxic mechanisms. Molecular mechanisms of cisplatininduced nephrotoxicity.
Nevertheless, nephrotoxicity has restricted its clinical use. The primary objective for this study was to determine whether mannitol or furosemide provides better nephroprotection when administered with hydration prior to weekly, low. To investigate the possible protective role of curcumin and. Cisplatin cp induced nephrotoxicity is widely accepted as a model for acute kidney injury aki.
Cisplatin nephrotoxicity as a model of chronic kidney disease. Nephrotoxicity can be defined as the adverse effect of substances on renal function perazella, 2009. Multiple pathways involved in cisplatininduced nephrotoxicity. Effects of cisplatininduced nephrotoxicity on gentamicin. The renoprotective effect of curcumin in cisplatininduced.
These substances can include molds and fungi, cancer therapeutics such as cisplatin, antibiotics such as aminoglycosides, metals such as mercury, arsenic and lead, and drugs of abuse such as cocaine. However, its clinical usage is restricted by serious adverse effects, especially nephrotoxicity. Male c57bl6 j mice were intraperitoneally administered with a single. Background nephrotoxicity remains a problem for patients who receive cisplatin chemotherapy. Cisplatin dose rate as a risk factor for nephrotoxicity in children. Evaluating dose of cisplatin responsible for causing. The major issues limiting the clinical use of csp are its tendency to induce profound nephrotoxicity and ototoxicity. Cisplatin induced nephrotoxicity is mediated by tumor necrosis factoralpha produced by renal parenchymal cells. The risk factors for cisplatin induced nephrotoxicity other than mg preloading were sex, ccr, coadministration of nsaids during the first cycle, hb and the coadministration of nsaids during all the cycles. Cisplatin is one of the most widely used and most potent chemotherapy drugs.
Download fulltext pdf download fulltext pdf download. As a highly effective antineoplastic chemotherapeutic drug, cisplatin is widely used clinically to treat a variety of human malignancies. We retrospectively evaluated potential risk factors for cisplatininduced nephrotoxicity as well as the potential impact of intravenous magnesium supplementation on such toxicity. Recent progress in the pathophysiology of acute renal failure. The findings highly suggested a translational potential of celastrol as a natural drug for.
Patients at highest risk of druginduced nephrotoxicity are those with one or more of the following. We focus on the docetaxel, cisplatin, and 5fluorouracil regimen, which is called the tpf regimen, where the standard dose of cisplatin is 60 mgm2. Effect of curcumin on inflammation and oxidative stress in. Amelioration of cisplatininduced nephrotoxicity in rats.
Although the exact mechanism of cisplatininduced nephrotoxicity cin is not understood, various processes, including local inflammation, oxidative stress, dna damage, and tubular epithelial cell apoptosis have been suggested 3,4. Recent evidence suggests that inflammation and oxidative stress may contribute to the pathogenesis of cisplatin induced acute renal failure. The aim of this study is to examine the relationship of the dosage of. Such druginduced nephrotoxicity, including acute tubular necrosis, inflammation, and altered hemodynamics such as reduction of renal blood flow by the inhibition of prostaglandin, might be associated with an increased risk for cin. Wed like to understand how you use our websites in order to improve them. Cisplatin induced injury to renal epithelial cells causes release of damps, which activate tlr4. The clinical use of cisplatin is associated with dose. Ltetrahydropalmatine attenuates cisplatininduced nephrotoxicity. Nov 15, 2007 nephrotoxicity is a major complication and a dose limiting factor for cisplatin therapy. Cisplatin cp is an antineoplastic agent that induces nephrotoxicity and oxidative stress.
Tnfr2mediated apoptosis and necrosis in cisplatin induced acute renal failure. Pdf cisplatininduced nephrotoxicity and targets of. Organic cation transporter 2 oct2 has been implicated in the cellular uptake of cisplatin, but its. Use of the chemotherapeutic agent cisplatin cddp in cancer patients is limited by the occurrence of acute kidney injury aki. The incidence of cin is 3060% in pediatric cancer patients who receive cisplatin. Lantana camara and cucurbita pepo and certain fractions derived from the defatted methanolic extract of l. Understanding the mechanism of cisplatin nephrotoxicity could lead to novel renoprotective interventions. In conclusion, mg preloading had a preventive effect on cisplatin induced nephrotoxicity. Male c57bl6 j mice were intraperitoneally administered with a. Mar 31, 2015 evaluation seminar on molecular mechanisms of drug induced nephrotoxicity. Cisplatin also activates egfrsrc triggering erk and caspase3 leading to apoptosis and cisplatin induced nephrotoxicity arany et al.
We present a series of three rare cases of cast nephropathy, two of which are hiv patients, and the third patient is receiving cisplatin based. Nephroprotective activity of methanolic extract of lantana. Bmediated inflammation and protecting mitochondrial function. While toxicities include ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions 1,2, the main doselimiting side effect of cisplatin is nephrotoxicity 3,4,5. Despite the significant strides that have been made in understanding the mechanisms underlying cspinduced renal toxicity, advances in developing.
Recent studies have improved our understanding of the molecular mechanisms of cisplatin induced nephrotoxicity and ototoxicity. We aimed to investigate the renoprotective effects of dendropanax morbifera water extract dm on cddpinduced aki. Although it is best known for dna damage, cisplatin also causes cytoplasmic organelle dysfunction particularly with the endoplasmic. Apr 29, 2014 cisplatin cp is an antineoplastic agent that induces nephrotoxicity and oxidative stress. For revealing the dose and timedependence of cisplatininduced nephrotoxicity, mass spectrometrybased metabolomics integrated with a principal componentbased area calculation pcac strategy was proposed in the present study. These substances can include molds and fungi, cancer therapeutics such as cisplatin, antibiotics such as aminoglycosides, metals such as mercury, arsenic and lead, and drugs of. Nephrotoxicity was evaluated using the kidney disease improving global outcomes kdigo 2012 acute kidney injury criteria and the national. The aim of this study is to evaluate the nephroprotective activity of defatted methanolic extract of two egyptian plants. Nephrotoxicity was reported in the initial clinical trials of cisplatin chemotherapy. The aim of this study is to evaluate the effect of mannitol on renal function and describe the incidence of cisplatininduced nephrotoxicity. Renal insufficiency can be prevented by hydration and forced disuresis. Plantderived agents for counteracting cisplatininduced.
Cisplatin csp is a chemotherapeutic agent commonly used to treat a variety of malignancies. Garlic powder ameliorates cisplatininduced nephrotoxicity. In summary, our study demonstrated that celastrol could ameliorate cisplatininduced nephrotoxicity by antagonizing nf. However, side effects in normal tissues and organs, notably nephrotoxicity in the kidneys, limit the use of cisplatin and related platinumbased therapeutics. Cisplatininduced injury to renal epithelial cells causes release of damps, which activate. Nephrotoxicity due to a aminoglycosides b cyclophosphamide c cisplatin d radiocontrast e analgesic f. Cytotoxicity of cisplatin there is convincing evidence that the primary biochemical lesion induced by cisplatin in cancer cells is inhibition of dna synthesis. Reactive oxygen species ros have been implicated in cisplatininduced nephrotoxicity. The ethanolic extract of the roots of hemidesmus indicus was investigated for its nephroprotective activity in cisplatin induced renal injury in rats. However, its nephrotoxic and ototoxic sideeffects remain major clinical limitations. Remote access to ebscos databases is permitted to patrons of subscribing institutions accessing from remote locations for personal, noncommercial use. Recent evidence suggests that inflammation and oxidative stress may contribute to the pathogenesis of cisplatininduced acute renal failure.
Curcumin is claimed to be a potent antiinflammatory and antioxidant agent. Cisplatin cisdiamminedichloroplatinumii, cddp is an antineoplastic drug used in the treatment of many solidorgan cancers, including those of the head, neck, lung, testis, ovary, and breast. The aim of this study was to investigate the potential of using 3hlabeled nmethyl2,3diamino6phenyldihydrophenanthridine 3hhydromethidine for ex vivo imaging of regional ros overproduction in mouse kidney induced by cisplatin. The renoprotective effect of curcumin in cisplatininduced nephrotoxicity. Protective effect of magnesium preloading on cisplatin. Pathophysiology of cisplatininduced acute kidney injury hindawi. In the present work the effect of garlic powder, a recognized antioxidant, on cisplatininduced nephrotoxicity and oxidative and nitrosative stress was. Cisplatininduced nephrotoxicity and hiv associated.
Cisplatin is a highly effective chemotherapeutic agent. Dhapc could protect the kidneys against cisplatininduced toxicity, which might be attributed to the sirtuin 1 activation and the inhibition of oxidative stress and apoptosis. The use of more than a few antioxidants has shown that reactive oxygen species are involved in cisplatininduced nephrotoxicity. The alleviation or prevention of cddpcaused nephrotoxicity is currently accomplished by. A retrospective evaluation of furosemide and mannitol for. Contribution of organic cation transporter 2 oct2 to. Cisplatin caused a significant decrease in gentamicin clearance. Dichloroacetate prevents cisplatininduced nephrotoxicity without. Despite intensive research, the mechanism of cisplatininduced nephrotoxicity remains unclear, and renoprotective approaches during cisplatinbased chemotherapy are. The major setback with csp treatment is that its clinical efficacy is compromised by its induction of organ toxicity, particular to the kidneys and ears. Magnesium supplementation therapy to prevent cisplatin. Cisplatin is a major antineo plastic drug for the treatment of solid tumors, but it has dosedependent renal toxicity.
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