Role of Ginsenoside-Rd in Cisplatin-Induced Renal Injury: Special Reference to DNA Fragmentation

Yokozawa, Takako; Dong, Erbo

doi:10.1159/000046116

Cited by 53 publications

(25 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Agarose gel electrophoresis was carried out for the analysis of DNA fragmentation by the method of Yokozawa and Dong, 2001 [40]. The DNA from Huh7 control cells and treated cells were isolated following the manufacturer’s instructions provided by the kit (Bangalore Genei) and dissolved in TE buffer.…”

Section: Methodsmentioning

confidence: 99%

Potential therapeutic role of Tridham in human hepatocellular carcinoma cell line through induction of p53 independent apoptosis

Jaganathan

Ravinayagam

Sachdanandam

et al. 2013

BMC Complement Altern Med

View full text Add to dashboard Cite

BackgroundHepatocellular carcinoma (HCC) is the third leading cause of cancer deaths reported worldwide. The incidence is higher in Asia and Africa, where there is greater endemic prevalence of hepatitis B and C. The devastating outcome of cancer can be minimized only by the use of potent therapeutic agents. Tridham (TD) has been acknowledged since olden days for its wide spectrum of biological properties and was used by traditional practitioners of Siddha and other indigenous systems of medicine. The present study aims at investigating the mechanistic action of TD by assessing the antiproliferative and pro-apoptotic effects on human hepatocellular carcinoma cell line (Huh7).MethodsCell viability and apoptosis assay using MTT analysis and trypan blue staining, DAPI staining, DNA fragmentation, cell cycle analysis, mitochondrial membrane potential, real-time reverse transcription-polymerase chain reaction, western blotting and immunofluorescence staining were determined in Huh7 cells.ResultsViability studies of TD treated Huh7 cells showed an inhibition in cell growth in time and dose dependent manner. Chromatin condensation, DNA fragmentation and apoptotic bodies, which are structural changes characteristic of apoptosis, were found following TD treatment of Huh7 cells. DAPI staining and agarose gel electrophoresis confirmed the induction of apoptosis by TD. Cell cycle analysis of Huh7 cells treated with TD exhibited a marked accumulation of cells in the sub-G1 phase of the cell cycle in a dose dependent manner. Immunofluorescent staining for Ki-67 showed a higher level of expression in untreated cells as compared to TD treated cells. We observed a significant loss in the mitochondrial membrane potential and the release of cytochrome c into the cytosol in TD treated cells. Down regulation of Bcl-2, up regulation of Bax and Bad as well as activation of caspases-3 and 9 were also observed. The p53 gene expression was found to be unaltered in TD treated cells.ConclusionThese results suggest that TD induces apoptosis of Huh7 cells through activation of Bax and triggered caspase cascade, independent of p53 function. This study throws light on the mechanistic action of TD in triggering apoptosis in Huh 7 cells.

show abstract

Section: Methodsmentioning

confidence: 99%

Potential therapeutic role of Tridham in human hepatocellular carcinoma cell line through induction of p53 independent apoptosis

Jaganathan

Ravinayagam

Sachdanandam

et al. 2013

BMC Complement Altern Med

View full text Add to dashboard Cite

show abstract

“…DNA was collected by centrifugation at 15,000 × g for 20 min, air-dried, and resuspended in TE buffer (10 mM Tris-HCl, 5 mM EDTA, pH 7.4). The resulting DNA preparations were electrophoresed through a 1.4% agarose gel containing ethidium bromide using TBE buffer (Tris-boric acid-EDTA buffer, pH 8.3) at 40 V for 5 h. Equal quantities of DNA (based on optical density measurements at 260 nm) were loaded in each lane, and a molecular DNA marker was used as a molecular mass standard (26). DNA fragmentation was visualized and photographed under ultraviolet illumination for testing the degree of fragmentation.…”

Section: Evaluation Of Dna Fragmentation In the Kidney Tissuesmentioning

confidence: 99%

Ameliorating effect of DL-α-lipoic acid against cisplatin-induced nephrotoxicity and cardiotoxicity in experimental animals

Hussein¹

2012

Drug Discov Ther

View full text Add to dashboard Cite

Cisplatin is a potent chemotherapeutic agent with a wide range of activities. Nephrotoxicity and cardiotoxicity represent it's major complication upon clinical use. The present study was carried out to evaluate the possible protective effect of DL-α-lipoic acid (LA) against cisplatin-induced nephrotoxicity and cardiotoxicity. Different groups of rats (n = 10) were administered either saline (control), cisplatin (10 mg/kg, i.p.), LA (100 mg/kg, i.p.) or their combination (LA 30 min prior to cisplatin administration). Twentyfour hours later all animals were decapitated and sera were used for estimation of activities of urea (BUN), creatinine (Cr), lactate dehydrogenase (LDH), and creatine kinase (CK). Homogenates of the kidney and heart were used for estimation of oxidative stress markers (reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO)). Additionally, caspase-3 activities and DNA-fragmentation were investigated in renal tissues. The results showed that cisplatin produced significant elevation in serum activities of LDH, CK, BUN, and Cr and also induced significant elevation in the oxidative stress makers (MDA and NO) accompanied by significant reduction in GSH and SOD in both kidney and heart. The integrity of DNA was heavily damaged and caspase-3 was activated in renal tissues. The results emphasized nephrotoxicty and cardiotoxicity of cisplatin. On the other hand, prior administration of LA significantly attenuated the cisplatin-evoked disturbances in the above mentioned parameters and protected both kidney and heart tissues. The histopathological examination emphasized the obtained results. In conclusion, LA is suggested to be a potential candidate to ameliorate cisplatininduced nephrotoxicity and cardiotoxicity without altering the antitumor efficacy of cisplatin.

show abstract

“…Furthermore, ginsenoside Rd ameliorates cisplatin-induced nephrotoxicity by suppression of apoptosis through the reduction of DNA fragmentation and leads to restoration of renal function in vivo. 11) From the relationship between the structure of ginsenosides and their antioxidant or prooxidant activity discussed above, ginsenosides Rh 4 and Rk 3 may act as antioxidants during the oxidative stress involved in cell death because of its structural similarity to ginsenoside Rh 1 . Ginsenosides Rh 4 and Rk 3 have a glucose moiety in the 6-position like Rh 1 , while Rh 4 and Rk 3 have a double bond at D20-21 and D20-22, respectively, and Rh 1 a hydroxyl in the 20-position.…”

Section: Resultsmentioning

confidence: 99%

Reduction of Cisplatin-Induced Nephrotoxicity by Ginsenosides Isolated from Processed Ginseng in Cultured Renal Tubular Cells

Baek

Piao

Lee

et al. 2006

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Ginseng, the root of Panax ginseng C. A. MEYER (Araliaceae), is one of the most widely prescribed and intensively studied herbal medicines. Ginsenosides, the secondary metabolites and unique constituents in the Panax plants, are the pharmacologically active ingredients of ginseng. There are two traditional preparations of ginseng, white ginseng (WG) and red ginseng (RG), the dried root of ginseng and the steamed/dried root of ginseng, respectively. RG especially shows more enhanced pharmacologic activities than WG.1) These enhanced pharmacologic activities result from the red ginseng unique ginsenosides (RGUG) produced during processing. It is reported that unique ginsenosides in red ginseng are ginsenosides Rg 3 , Rg 5 , Rg 6 , Rh 2 , Rh 3 , Rh 4 , Rs 3 , and F 4 . 1,2) Recently, our research group has developed a new processed ginseng, called Sun ginseng (SG), by steaming WG at high temperature and pressure.1) HPLC-evaporative light scattering detector (ELSD) analysis of ginsenosides in SG revealed that SG had hundreds of times more RGUG than RG.1,3) A preparation containing SG extracts with specific standardization is now available as a functional food on the Korean market.Cisplatin [cis-dichlorodiammine-platinum(II)] is an antineoplastic agent clinically used in the treatment of various solid tumors such as testis, ovary, urinary bladder, prostate, head, and neck cancer. However, despite its excellent anticancer activity, its clinical use is limited because of severe nephrotoxicity. 4,5) The nephrotoxicity induced by cisplatin is characterized by morphologic destruction of intracellular organelles, such as cellular necrosis, loss of microvilli, alterations in the number and size of lysosomes, and mitochondrial vacuolization, followed by functional alterations including inhibition of protein synthesis, glutathione (GSH) depletion, lipid peroxidation, and mitochondrial damage. 5) Cisplatin is preferentially uptaken and accumulated in cells of the renal proximal tubules, and intracellular cisplatin is thought to undergo aquation reactions in which the labile chloride ligands are replaced by water molecules, resulting in a positively charged and highly reactive electrophilic product.4) This toxic derivative is thought to cause the oxidative damage in renal proximal tubular cells, resulting in cell death.From many reported in vitro and/or in vivo studies, there are several candidates of herbal origin that may reduce cisplatin nephrotoxicity. Quercetin, a common antioxidant bioflavonoid in fruit and vegetables, has potent cytoprotective effects against cisplatin nephrotoxicity in cultured renal proximal tubular epithelial cells (LLC-PK 1 ).6) A tannin mixture fractionated from green tea increased the viability of cells exposed to cisplatin in a dose-dependent manner in LLC-PK 1 in vitro and decreased blood levels of urea nitrogen and creatinine and urinary levels of protein and glucose in a rat model in vivo. Rats administrated the green tea tannin mixture were found to have increased activity of catalase in the r...

show abstract

Role of Ginsenoside-Rd in Cisplatin-Induced Renal Injury: Special Reference to DNA Fragmentation

Cited by 53 publications

References 9 publications

Potential therapeutic role of Tridham in human hepatocellular carcinoma cell line through induction of p53 independent apoptosis

Potential therapeutic role of Tridham in human hepatocellular carcinoma cell line through induction of p53 independent apoptosis

Ameliorating effect of DL-α-lipoic acid against cisplatin-induced nephrotoxicity and cardiotoxicity in experimental animals

Reduction of Cisplatin-Induced Nephrotoxicity by Ginsenosides Isolated from Processed Ginseng in Cultured Renal Tubular Cells

Contact Info

Product

Resources

About