Chemotherapy-Induced Toxicity: Cisplatin https://greenmedinfo.com/category/keywords/Chemotherapy-Induced%20Toxicity%3A%20Cisplatin en A short hydration regimen with magnesium supplementation prevents cisplatin-induced nephrotoxicity https://greenmedinfo.com/article/short-hydration-regimen-magnesium-supplementation-prevents-cisplatin-induced-n n/a PMID:  Support Care Cancer. 2016 Dec 13. Epub 2016 Dec 13. PMID: 27966021 Abstract Title:  Short hydration regimen with magnesium supplementation prevents cisplatin-induced nephrotoxicity in lung cancer: a retrospective analysis. Abstract:  PURPOSE: The purpose of this study was to evaluate renal function in lung cancer patients who were administered cisplatin with continuous higher-volume hydration (CH) or a short hydration (SH) regimen. METHODS: We retrospectively evaluated patients with lung cancer who were treated with chemotherapy regimens including>50 mg/m(2) of cisplatin between August 2007 and March 2015. Between August 2007 and December 2012, patients received a continuous higher-volume hydration regimen without magnesium (Mg) supplementation (CH group), and after May 2013, patients received a short hydration regimen with Mg supplementation(SH group). To evaluate the factors influencing serum creatinine (SCr) increase during the first course of cisplatin chemotherapy, univariate and multivariate logistic regression analyses were conducted. RESULTS: A total of 122 patients were evaluated, 62 patients in the CH group and 60 patients in the SH group. Grade 1 (National Cancer Institute Common Toxicity Criteria for Adverse Events; version 4.0) or higher SCr increases were more frequently observed in the CH group than in the SH group after the first cycle (P = 0.01, Fisher's exact test) and for all cycles (P = 0.03). Multivariate analysis revealed that short hydration (odds ratio (OR), 0.30; 95% confidence internal (CI) (0.11-0.75), P = 0.01) and estimated creatinine clearance (eCcr) of ≥70 mL/min (OR, 0.25; 95% CI (0.088-0.69), P = 0.008) were associated with a significantly reduced risk for cisplatin-induced grade 1 or higher SCr increase. CONCLUSION: Our study suggested that a short hydration method with Mg supplementation and eCcr of≥70 mL/min reduced the risk of cisplatin-induced nephrotoxicity. https://greenmedinfo.com/article/short-hydration-regimen-magnesium-supplementation-prevents-cisplatin-induced-n#comments Chemotherapy-Induced Toxicity: Cisplatin Magnesium Chemoprotective Agents Chemoprotective Agents Chemotherapy-Induced Toxicity: Cisplatin Magnesium Human Study Wed, 11 Jan 2017 01:02:19 +0000 greenmedinfo 141834 at https://greenmedinfo.com Ginsenosides Rk2 and Rh3 have kidney protective effects of against cisplatin. https://greenmedinfo.com/article/ginsenosides-rk2-and-rh3-have-kidney-protective-effects-against-cisplatin n/a PMID:  J Ginseng Res. 2017 Apr ;41(2):227-231. Epub 2017 Jan 23. PMID: 28413329 Abstract Title:  Protective effect of ginsenoside Rh3 against anticancer drug-induced apoptosis in LLC-PK1 kidney cells. Abstract:  BACKGROUND: Ginsenosides are active components of Panax ginseng that exert various health benefits including kidney protection effect. The medicinal activity of ginsenosides can be enhanced by modulating their stereospecificity by heat processing. Ginsenosides Rk2 and Rh3 represent positional isomers of the double bond at C-20(21) or C-20(22). METHODS: The present study investigated the kidney-protective effects of ginsenosides Rk2 and Rh3 against cisplatin, a platinum based anticancer drug, induced apoptotic damage in renal proximal LLC-PK1 cells. RESULTS: As a result, ginsenoside Rh3 shows a stronger protective effect than that shown by Rk2. Cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38, and cleaved caspase-3 decreased after cotreatment with ginsenoside Rh3. The increase in the percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment also significantly reduced after cotreatment with ginsenoside Rh3. CONCLUSION: These results demonstrate that inhibition of the JNK and ERK mitogen-activated protein kinase signaling cascade plays a critical role in mediating the renoprotective effect of ginsenoside Rh3. https://greenmedinfo.com/article/ginsenosides-rk2-and-rh3-have-kidney-protective-effects-against-cisplatin#comments Chemotherapy-Induced Toxicity: Cisplatin Ginsenosides Chemoprotective Agents Renoprotective Chemoprotective Agents Chemotherapy-Induced Toxicity: Cisplatin Ginsenosides Renoprotective In Vitro Study Fri, 12 May 2017 21:13:51 +0000 greenmedinfo 147681 at https://greenmedinfo.com Ginsenosides Rk3 and Rh4 protect the kidney from cisplatin-induced oxidative injury. https://greenmedinfo.com/article/ginsenosides-rk3-and-rh4-protect-kidney-cisplatin-induced-oxidative-injury n/a PMID:  J Ginseng Res. 2017 Jul ;41(3):233-239. Epub 2016 Apr 6. PMID: 28701862 Abstract Title:  Protective effect of ginsenosides Rk3 and Rh4 on cisplatin-induced acute kidney injury in vitro and in vivo. Abstract:  BACKGROUND: Nephrotoxicity is the major side effect in cisplatin chemotherapy. Previously, we reported that the ginsenosides Rk3 and Rh4 reduced cisplatin toxicity on porcine renal proximal epithelial tubular cells (LLC-PK1). Here, we aimed to evaluate the protective effect of ginsenosides Rk3 and Rh4 on kidney function and elucidate their antioxidant effect using in vitro and in vivo models of cisplatin-induced acute renal failure. METHODS: An enriched mixture of ginsenosides Rk3 and Rh4 (KG-KH; 49.3% and 43.1%, respectively) was purified from sun ginseng (heat processed Panax ginseng). Cytotoxicity was induced by treatment of 20μM cisplatin to LLC-PK1 cells and rat model of acute renal failure was generated by single intraperitoneal injection of 5 mg/kg cisplatin. Protective effects were assessed by determining cell viability, reactive oxygen species generation, blood urea nitrogen, serum creatinine, antioxidant enzyme activity, and histopathological examination. RESULTS: The in vitro assay demonstrated that KG-KH (50 μg/mL) significantly increased cell viability (4.6-fold), superoxide dismutase activity (2.8-fold), and glutathione reductase activity (1.5-fold), but reduced reactive oxygen species generation (56%) compared to cisplatin control cells. KG-KH (6 mg/kg, per os) also significantly inhibited renal edema (87% kidney index) and dysfunction (71.4% blood urea nitrogen, 67.4% creatinine) compared to cisplatin control rats. Of note, KG-KH significantly recovered the kidney levels of catalase (1.2-fold) and superoxide dismutase (1.5-fold). CONCLUSION: Considering the oxidative injury as an early trigger of cisplatin nephrotoxicity, our findings suggest that ginsenosides Rk3 and Rh4 protect the kidney from cisplatin-induced oxidative injury and help to recover renal function by restoring intrinsic antioxidant defenses. https://greenmedinfo.com/article/ginsenosides-rk3-and-rh4-protect-kidney-cisplatin-induced-oxidative-injury#comments Chemotherapy-Induced Toxicity: Cisplatin Ginsenosides Antioxidants Chemoprotective Agents Renoprotective Antioxidants Chemoprotective Agents Chemotherapy-Induced Toxicity: Cisplatin Ginsenosides Renoprotective Animal Study In Vitro Study Thu, 03 Aug 2017 16:58:04 +0000 greenmedinfo 151157 at https://greenmedinfo.com Neferine reduces cisplatin-induced nephrotoxicity by enhancing autophagy. https://greenmedinfo.com/article/neferine-reduces-cisplatin-induced-nephrotoxicity-enhancing-autophagy n/a PMID:  Biochem Biophys Res Commun. 2017 Mar 11 ;484(3):694-701. Epub 2017 Feb 1. PMID: 28161641 Abstract Title:  Neferine reduces cisplatin-induced nephrotoxicity by enhancing autophagy via the AMPK/mTOR signaling pathway. Abstract:  Cisplatin is one of the most effective chemotherapeutic agents; however, its clinical use is limited by serious side effects of which nephrotoxicity is the most important. Nephrotoxicity induced by cisplatin is closely associated with autophagy reduction and caspase activation. In this study, we investigated whether neferine, an autophagy inducer, had a protective effect against cisplatin-induced nephrotoxicity. In an in vitro cisplatin-induced nephrotoxicity model, we determined that neferine was able to induce autophagy and that pretreatment with neferine not only attenuated cisplatin-induced cell apoptosis but further activated cell autophagy. This pro-survival effect was abolished by the autophagic flux inhibitor chloroquine. Furthermore, neferine pretreatment activated the AMPK/mTOR pathway; however, pharmacological inhibition of AMPK abolished neferine-mediated autophagy and nephroprotection against cisplatin-induced apoptosis. Collectively, our findings suggest for the first time the possible protective mechanism of neferine, which is crucial for its further development as a potential therapeutic agent for cisplatin-induced nephrotoxicity. https://greenmedinfo.com/article/neferine-reduces-cisplatin-induced-nephrotoxicity-enhancing-autophagy#comments Chemotherapy-Induced Toxicity: Cisplatin Lotus Autophagy Up-regulation Chemoprotective Agents Autophagy Up-regulation Chemoprotective Agents Chemotherapy-Induced Toxicity: Cisplatin Lotus In Vitro Study Tue, 21 Feb 2017 18:18:24 +0000 greenmedinfo 143795 at https://greenmedinfo.com Nigella sativa oil and thymoquinone maybe useful in amelioration of the intestinal toxicity associated with long-term cisplatin chemotherapy. https://greenmedinfo.com/article/nigella-sativa-oil-and-thymoquinone-maybe-useful-amelioration-intestinal-toxic n/a PMID:  Naunyn Schmiedebergs Arch Pharmacol. 2018 Jan 4. Epub 2018 Jan 4. PMID: 29302711 Abstract Title:  Oral Nigella sativa oil and thymoquinone administration ameliorates the effect of long-term cisplatin treatment on the enzymes of carbohydrate metabolism, brush border membrane, and antioxidant defense in rat intestine. Abstract:  We have previously shown that oral administration of Nigella sativa oil (NSO) ameliorates the deleterious gastrointestinal effects of cisplatin (CP), administered as a single dose. Since a typical clinical CP dosing regimen involves multiple cycles of CP administration in lower doses, in the present study we investigate the protective efficacy of NSO and its major bioactive constituent, thymoquinone (TQ), against multiple-dose CP treatment-induced deleterious biochemical and histological changes in rat intestine. Rats were divided into six groups, viz., control, CP, CP+NSO, CP+TQ, NSO, and TQ. Animals in CP+NSO and CP+TQ groups were pre-administered NSO (2 ml/kg bwt, orally) and TQ (1.5 mg/kg bwt, orally), respectively, daily for 14 days and were then treated with five repeated doses of CP (3 mg/kg bwt, i.p.), every fourth day for 20 days while still receiving NSO/TQ. CP treatment alone led to a significant decline in specific activities of brush border membrane (BBM) enzymes while NSO or TQ administration to CP-treated rats significantly prevented the decline in BBM enzyme activities in the isolated brush border membrane vesicles (BBMV) as well as in mucosal homogenates. Furthermore, both NSO and TQ administration markedly ameliorated CP-induced alterations on carbohydrate metabolism enzymes and the enzymatic and non-enzymatic parameters of antioxidant defense system in the intestinal mucosa. However, NSO appeared to be more efficacious than TQ in protecting against CP-induced gastrointestinal dysfunction. Histopathological findingscorroborated the biochemical results. Thus, NSO and TQ may prove clinically useful in amelioration of the intestinal toxicity associated with long-term CP chemotherapy. https://greenmedinfo.com/article/nigella-sativa-oil-and-thymoquinone-maybe-useful-amelioration-intestinal-toxic#comments Chemotherapy-Induced Toxicity: Cisplatin Nigella sativa (aka Black Seed) Thymoquinone Chemoprotective Agents Chemoprotective Agents Chemotherapy-Induced Toxicity: Cisplatin Nigella sativa (aka Black Seed) thymoquinone Animal Study Tue, 09 Jan 2018 17:39:13 +0000 greenmedinfo 158242 at https://greenmedinfo.com Nigella sativa oil may help prevent the accompanying gastrointestinal dysfunction in cisplatin chemotherapy. https://greenmedinfo.com/article/nigella-sativa-oil-may-help-prevent-accompanying-gastrointestinal-dysfunction- n/a PMID:  Exp Toxicol Pathol. 2017 Feb 15. Epub 2017 Feb 15. PMID: 28215571 Abstract Title:  Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on brush border membrane enzymes, carbohydrate metabolism and antioxidant system in rat intestine. Abstract:  Cisplatin (CP) is an effective chemotherapeutic agent that induces gastrointestinal toxicity. Nigella sativa oil (NSO) has been shown to be beneficial in a wide range of gastrointestinal disorders. The present study investigates the possible protective effect of NSO on CP-induced gastrointestinal toxicity. NSO administration (2ml/kg bwt, orally), prior to and following, a single dose CP treatment (6mg/kg bwt. ip), significantly attenuated the CP-induced decrease in brush border membrane (BBM) enzyme activities in intestinal homogenates and BBM vesicles (BBMV). NSO administration also mitigated CP induced alterations in the activities of carbohydrate metabolism enzymes and in the enzymatic and non-enzymatic antioxidant parameters in the intestine. The results suggest that NSO by empowering the endogenous antioxidant system improves intestinal redox and metabolic status and restores BBM integrity in CP treated rats. Histopathological studies supported the biochemical findings. Thus, NSO may help prevent the accompanying gastrointestinal dysfunction in CP chemotherapy. https://greenmedinfo.com/article/nigella-sativa-oil-may-help-prevent-accompanying-gastrointestinal-dysfunction-#comments Chemotherapy-Induced Toxicity: Cisplatin Nigella sativa (aka Black Seed) Chemoprotective Agents Gastroprotective Chemoprotective Agents Chemotherapy-Induced Toxicity: Cisplatin Gastroprotective Nigella sativa (aka Black Seed) Animal Study Wed, 15 Mar 2017 20:44:42 +0000 greenmedinfo 144868 at https://greenmedinfo.com Panax ginseng anthocyanins pre-administration can significantly prevent cisplatin-induced nephrotoxicity. https://greenmedinfo.com/article/panax-ginseng-anthocyanins-pre-administration-can-significantly-prevent-cispla n/a PMID:  Phytother Res. 2017 Jul 21. Epub 2017 Jul 21. PMID: 28731262 Abstract Title:  Nephroprotective Effects of Anthocyanin from the Fruits of Panax ginseng (GFA) on Cisplatin-Induced Acute Kidney Injury in Mice. Abstract:  Cisplatin is an effective anticancer chemotherapeutic agent, but the use of cisplatin in the clinic is severely limited by side effects. Nephrotoxicity is a major factor that contributes to the side effects of cisplatin chemotherapy. The aim of this research was to survey the nephroprotective effects of anthocyanin from the fruits of Panax ginseng (GFA) in a murine model of cisplatin-induced acute kidney injury. We observed that pretreatment with GFA attenuated cisplatin-induced elevations in blood urea nitrogen and creatinine levels and histopathological injury induced by cisplatin. The formation of kidney malondialdehyde, heme oxygenase-1, cytochrome P450 E1 and 4-hydroxynonenal with a concomitant reduction in reduced glutathione was also inhibited by GFA, while the activities of kidney superoxide dismutase and catalase were all increased. GFA also inhibited the increase in serum tumour necrosis factor-α and interleukin-1β induced by cisplatin. In addition, the levels of induced nitric oxide synthase and cyclooxygenase-2 were suppressed by GFA. Furthermore, GFA supplementation inhibited the activation of apoptotic pathways by increasing B cell lymphoma 2 and decreasing Bcl2-associated X proteinexpression. In conclusion, the findings from the present investigation demonstrate that GFA pre-administration can significantly prevent cisplatin-induced nephrotoxicity, which may be related to its antioxidant, anti-apoptotic and antiinflammatory effects. Copyright © 2017 John Wiley&Sons, Ltd. https://greenmedinfo.com/article/panax-ginseng-anthocyanins-pre-administration-can-significantly-prevent-cispla#comments Anthocyanins Chemotherapy-Induced Toxicity: Cisplatin Panax Ginseng Chemoprotective Agents Cyclooxygenase 2 Inhibitors Nitric Oxide Inhibitor Anthocyanins Chemoprotective Agents Chemotherapy-Induced Toxicity: Cisplatin Cyclooxygenase 2 Inhibitors Nitric Oxide Inhibitor Panax Ginseng Animal Study Thu, 03 Aug 2017 17:30:59 +0000 greenmedinfo 151161 at https://greenmedinfo.com Phloretin has an anti-apoptotic effect on cisplatin-induced apoptosis in HEI-OC1 auditory cells. https://greenmedinfo.com/article/phloretin-has-anti-apoptotic-effect-cisplatin-induced-apoptosis-hei-oc1-audito n/a PMID:  Pharmacol Rep. 2011 ;63(3):708-16. PMID: 21857081 Abstract Title:  Anti-apoptotic effect of phloretin on cisplatin-induced apoptosis in HEI-OC1 auditory cells. Abstract:  Cisplatin is a highly effective chemotherapeutic agent, but it has significant ototoxic side effects. Apoptosis is an important mechanism of cochlear hair cell loss following exposure to cisplatin. The present study examined the effects of phloretin, a natural polyphenolic compound found in apples and pears, on cisplatin-induced apoptosis. We found that phloretin induced the expression of heme oxygenase-1 (HO-1) protein in a concentration- and time-dependent manner. Phloretin induced nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation, and dominant-negative Nrf2 attenuated phloretin-induced expression of HO-1. Phloretin activated the JNK, ERK and p38 mitogen-activated protein kinase (MAPK) pathways, and the JNK pathway played an important role in phloretin-induced HO-1 expression. Phloretin protected the cells against cisplatin-induced apoptosis. The protective effect of phloretin was abrogated by zinc protoporphyrin IX (ZnPP IX), a HO inhibitor. Furthermore, phloretin pretreatment inhibited mitochondrial dysfunction and the activation of caspases. These results demonstrate that the expression of HO-1 induced by phloretin is mediated by both the JNK pathway and Nrf2; the expression inhibits cisplatin-induced apoptosis in HEI-OC1 cells. https://greenmedinfo.com/article/phloretin-has-anti-apoptotic-effect-cisplatin-induced-apoptosis-hei-oc1-audito#comments Chemotherapy-Induced Toxicity: Cisplatin Phloretin Anti-Apoptotic Chemoprotective Agents Heme oxygenase-1 inducer Anti-Apoptotic Chemoprotective Agents Chemotherapy-Induced Toxicity: Cisplatin Heme oxygenase-1 inducer Phloretin In Vitro Study Fri, 03 Mar 2017 22:20:44 +0000 greenmedinfo 144372 at https://greenmedinfo.com Tangeretin not only enhanced cisplatin’s cytotoxic actions in Hep3B and HCT-116 human cancer cells but could protect against its harmful effects. https://greenmedinfo.com/article/tangeretin-not-only-enhanced-cisplatin-s-cytotoxic-actions-hep3b-and-hct-116-h n/a PMID:  Chem Biol Interact. 2016 Oct 25 ;258:205-13. Epub 2016 Sep 9. PMID: 27616468 Abstract Title:  Tangeretin attenuates cisplatin-induced renal injury in rats: Impact on the inflammatory cascade and oxidative perturbations. Abstract:  BACKGROUND: Despite the efficacy of cisplatin as a chemotherapeutic agent against various cancers, its clinical utility is limited by serious adverse reactions including nephrotoxicity. AIM: The current study aims to investigate the protective potential of tangeretin, a citrus flavone with marked antioxidant actions, against cisplatin-induced renal injury in rats. METHODS: Tangeretin was administered at 50 and 100 mg/kg p.o. for 1 week starting one day before cisplatin (7.5 mg/kg i.p.) injection. Likewise, silymarin was administered at 100 mg/kg orally. Renal function tests, histopathology, oxidative stress and inflammatory events were investigated. RESULTS: Tangeretin mitigated the increased levels of serum creatinine, blood urea nitrogen and histopathologic alterations evoked by cisplatin. It alleviated renal oxidative stress due to cisplatin by lowering lipid peroxides, nitric oxide and Nrf2 levels with concomitant enhancement of GSH and GPx. Tangeretin also suppressed the upregulated inflammatory response seen with cisplatin treatment by downregulation of activated NF-κB p65 protein expression together with its downstream effectors e.g., iNOS and TNF-α, with restoration of the anti-inflammatory interleukin IL-10. Additionally, it down-regulated the expression of caspase-3, an apoptotic marker, thus favoring renal cell survival. Importantly, tangeretin enhancedthe cytotoxic actions of cisplatin in Hep3B and HCT-116 human cancer cell lines. CONCLUSION: Together, these findings accentuate the dual benefit of tangeretin: mitigation of renal injury-induced by cisplatin and enhancement of its cytotoxic effects. https://greenmedinfo.com/article/tangeretin-not-only-enhanced-cisplatin-s-cytotoxic-actions-hep3b-and-hct-116-h#comments Chemotherapy-Induced Toxicity: Cisplatin Inflammation Lipid Peroxidation Oxidative Stress Tangeretin Anti-Inflammatory Agents Antioxidants Chemoprotective Agents Interleukin-10 upregulation NF-kappaB Inhibitor Tumor Necrosis Factor (TNF) Alpha Inhibitor Chemotherapeutic Synergy: Cisplatin Chemotherapy-Induced Toxicity: Cisplatin Inflammation Lipid Peroxidation oxidative stress Tangeretin In Vitro Study Wed, 10 May 2017 01:19:31 +0000 greenmedinfo 147521 at https://greenmedinfo.com These results highlight the protective effects of tangeretin against cisplatin-induced acute hepatic injury. https://greenmedinfo.com/article/these-results-highlight-protective-effects-tangeretin-against-cisplatin-induce n/a PMID:  PLoS One. 2016 ;11(3):e0151649. Epub 2016 Mar 31. PMID: 27031695 Abstract Title:  Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting MAPKs and Apoptosis. Abstract:  Despite its broad applications, cisplatin affords considerable nephro- and hepatotoxicity through triggering inflammatory and oxidative stress cascades. The aim of the current investigation was to study the possible protective effects of tangeretin on cisplatin-induced hepatotoxicity. The impact of tangeretin on cisplatin-evoked hepatic dysfunction and histopathologic changes along with oxidative stress, inflammatory and apoptotic biomarkers were investigated compared to silymarin. Tangeretin pre-treatment significantly improved liver function tests (ALT and AST), inhibited cisplatin-induced lipid profile aberrations (total cholesterol and triglycerides) and diminished histopathologic structural damage in liver tissues. Tangeretin also attenuated cisplatin-induced hepatic inflammatory events as indicated by suppression of tumor necrosis factor-α (TNF-α) and enhancement of interleukin-10 (IL-10). Meanwhile, it lowered malondialdehyde (MDA), nitric oxide (NO) and nuclear factor erythroid 2-related factor 2 (NRF-2) levels with restoration of glutathione (GSH), and glutathione peroxidase (GPx). Regarding mitogen-activated protein kinase (MAPK) pathway, tangeretin attenuated cisplatin-induced increase in phospho-p38, phospho-c-Jun N-terminal kinase (p-JNK) and phospho-extracellular signal-regulated kinase (p-ERK1/2) in liver tissues. In addition, tangeretin downregulated Bax expression with augmentation of Bcl-2 promoting liver cell survival. Our results highlight the protective effects of tangeretin against cisplatin-induced acute hepatic injury via the concerted modulation of inflammation, oxidative stress, MAPKs and apoptotic pathways. https://greenmedinfo.com/article/these-results-highlight-protective-effects-tangeretin-against-cisplatin-induce#comments Chemotherapy-Induced Toxicity: Cisplatin Tangeretin Anti-Apoptotic Anti-Inflammatory Agents Antioxidants Chemoprotective Agents Anti-Apoptotic Anti-Inflammatory Agents Antioxidants Chemoprotective Agents Chemotherapy-Induced Toxicity: Cisplatin Animal Study Tue, 23 Jan 2018 15:38:58 +0000 greenmedinfo 158683 at https://greenmedinfo.com