Effects of sodium thiosulfate on the pharmacokinetics of unchanged cisplatin and on the distribution of platinum species in rat kidney: protective mechanism against cisplatin nephrotoxicity

1995 ◽  
Vol 36 (5) ◽  
pp. 404-410 ◽  
Author(s):  
Naomi Nagai ◽  
Kazuhiro Hotta ◽  
Hidetoshi Yamamura ◽  
Hiroyasu Ogata
Keyword(s):  
Rat Kidney ◽  
Sodium Thiosulfate ◽  
Protective Mechanism ◽  
Cisplatin Nephrotoxicity ◽  
Unchanged Cisplatin ◽  
Platinum Species

scholarly journals Analysis of microRNA Expression after Glutamine Intervention in Acute Renal Ischemia-Reperfusion Injury

2022 ◽  
Vol 2022 ◽  
pp. 1-7
Author(s):  
Suhua Li ◽  
Xuan Huang ◽  
Shun Wang ◽  
Xueqian Chu ◽  
Munire Aierken
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Rat Kidney ◽  
Ischemia Reperfusion ◽  
Kidney Tissue ◽  
Akt Signaling ◽  
Protective Mechanism ◽  
Renal Tubules ◽  
Akt Signaling Pathway

Background. Ischemia-reperfusion acute kidney injury (I/R AKI) is a severe kidney disease with high mortality and morbidity. This study aimed to explore the protective mechanism of glutamine (GLN) against I/R AKI. Methods.The I/R AKI rat model was established, and HE staining of kidney tissue and serum creatinine (SCr) and blood urea nitrogen (BUN) detection were performed. The miRNAs were sequenced by high throughput in rat kidney tissue samples. Differentially expressed miRNAs (DEmiRs) between the I/R group and I/R + GLN group were screened, and enrichment analysis for target genes of DEmiRs was performed. Meanwhile, human HK-2 cells were cultured, and an I/R model was established to verify the expression of DEmiRs. Results. Compared with the I/R group, the SCr and BUN levels at each time point were lower in the I/R + GLN group. Vacuolar degeneration of renal tubules in the I/R + GLN group was significantly reduced. In the 104 DEmiRs, we selected miR-132-5p, miR-205, and miR-615 as key miRNAs. KEGG analysis showed that the Notch signaling pathway, PI3K-Akt signaling pathway, and cGMP signaling pathway were mainly related to the GLN against I/R. qRT-PCR verified the downregulation of miR-205 in the I/R group, compared to the sham and I/R + GLN group. The I/R model was established with HK-2 cells, and the expression of miR-132-5p and miR-205 was decreased. Conclusion. GLN reduced I/R-induced AKI. There were significant differences between miRNAs expression in I/R after GLN treatment. The process of GLN against I/R-induced AKI may be related to the Notch and PI3K-Akt signaling pathway.

Tiopronin protects against the nephrotoxicity of cisplatin in the rat

1999 ◽  
Vol 18 (12) ◽  
pp. 713-717 ◽  
Author(s):  
J-G Zhang ◽  
M Viale ◽  
M Esposito ◽  
W E Lindup
Keyword(s):  
Body Weight ◽  
Antitumour Activity ◽  
Rat Kidney ◽  
The Body ◽  
Albino Rats ◽  
Protective Effects ◽  
Kidney Weight ◽  
Plasma Urea ◽  
Cisplatin Nephrotoxicity

1 Tiopronim (N-(2-mercaptopropionyl)-glycine) is a drug with a free thiol (sulphydryl) group that is used clinically. We have reported previously that tiopronin protects rat kidney slices in vitro from the nephrotoxic effects of cisplatin and does not reduce the antitumour activity of cisplatin. Tiopronin has been investigated therefore for its protective effects in rats in vivo. 2 The extent of kidney damage was studied 5 days after the administration of cisplatin. A single injection (i.p.) of cisplatin (6 mg/kg; 20,umollkg) to female Wistar albino rats caused a sustained decrease in body weight and, after 5 days, plasma urea, creatinine and kidney weight were increased. Tiopronin (2.5 mmol/kg, p.o.) ameliorated cisplatin nephrotoxicity when given 1 h before cisplatin. Tiopronin provided marked protection against cisplatin-induced increases in urea (from 237+19 mg to 48+23 mg/100 ml; control: 17+1) and creatinine (from 6.5+0.5 to 1.7+0.5 mg/100 ml control: 1.0 + 0.1). Tiopronin did not, prevent the body weight loss caused by cisplatin. In addition, an intraperitoneal dose (1 mmol/lkg) oftiopronin afforded similar protection to that of an oral dose. Rats that received an i.p. mixture of cisplatin (6 mg/kg) and tiopronin (65 mg/kg) displayed generally less toxicity, as indicated by a small fall in body weight and smaller increases in urea and creatinine and kidney weight. 3 The results show that tiopronin protects against cisplatin-induced nephrotoxicity. Oral administration of tiopronin may be a clinically useful way to prevent cisplatin nephrotoxicity.

Effect of Glycine on Cisplatin Nephrotoxicity and Heat-Shock Protein 70 Expression in the Rat Kidney

Renal Failure ◽  
1997 ◽  
Vol 19 (1) ◽  
pp. 33-46 ◽  
Author(s):  
Franco Musio ◽  
Michael A. Carome ◽  
Erin M. Bohen ◽  
Sharda Sabnis ◽  
Christina M. Yuan
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Rat Kidney ◽  
Cisplatin Nephrotoxicity

scholarly journals Pretreatment with Oxygen Protects Rat Kidney from Cisplatin Nephrotoxicity

Renal Failure ◽  
2010 ◽  
Vol 32 (2) ◽  
pp. 234-242 ◽  
Author(s):  
Bahram Rasoulian ◽  
Mahvash Jafari ◽  
Mirgholamreza Mahbod ◽  
Mansour Esmaili Dehaj ◽  
Majid Nowrozi ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Cisplatin Nephrotoxicity

scholarly journals Expression of the RNA-stabilizing protein HuR in ischemia-reperfusion injury of rat kidney

2009 ◽  
Vol 297 (1) ◽  
pp. F95-F105 ◽  
Author(s):  
Dina A. Ayupova ◽  
Mamata Singh ◽  
Ellen C. Leonard ◽  
David P. Basile ◽  
Beth S. Lee
Keyword(s):  
Proximal Tubule ◽  
Translational Control ◽  
Rna Binding ◽  
Ischemia Reperfusion Injury ◽  
Rat Kidney ◽  
Ischemia Reperfusion ◽  
Proximal Tubules ◽  
Protective Mechanism ◽  
Proximal Tubule Cell

The RNA-binding protein human antigen R (HuR) participates in the posttranscriptional regulation of mRNAs bearing 3′ AU-rich and U-rich elements, which HuR can stabilize under conditions of cellular stress. Using the LLC-PK1 proximal tubule cell line model, we recently suggested a role for HuR in protecting kidney epithelia from injury during ischemic stress (Jeyaraj S, Dakhlallah D, Hill SR, Lee BS. J Biol Chem 280: 37957–37964, 2005; Jeyaraj SC, Dakhlallah D, Hill SR, Lee BS. Am J Physiol Renal Physiol 291: F1255–F1263, 2006). Here, we have extended this work to show that small interfering RNA-mediated suppression of HuR in LLC-PK1 cells increased apoptosis during energy depletion, while overexpression of HuR diminished apoptosis. Suppression of HuR also resulted in diminished levels of key cell survival proteins such as Bcl-2 and Hsp70. Furthermore, rat kidneys were subjected in vivo to transient ischemia followed by varying periods of reperfusion. Ischemia and reperfusion (I/R) affected intensity and distribution of HuR in a nephron segment-specific manner. Cells of the proximal tubule, which are most sensitive to I/R injury, demonstrated a transient shift of HuR to the cytoplasm immediately following ischemia. Over a 14-day period following the onset of reperfusion, nuclear and total HuR protein gradually increased in cortical and medullary proximal tubules, but not in non-proximal tubule cells. HuR mRNA was expressed in two forms with alternate transcriptional start sites that increased over a 14-day I/R period, and in vitro studies suggest selective translatability of these two mRNAs. Baseline and I/R-stimulated levels of HuR mRNA did not parallel those of HuR protein, suggesting translational control of HuR expression, particularly in medullary proximal tubules. These findings suggest that alterations in distribution and expression of the antiaptotic protein HuR specifically in cells of the proximal tubule effect a protective mechanism during and following I/R injury in kidney.

Newer Insights into Cisplatin Nephrotoxicity

1993 ◽  
Vol 27 (12) ◽  
pp. 1519-1525 ◽  
Author(s):  
Edward A. Hartshorn ◽  
Ajay J. Anand ◽  
Baquar Bashey
Keyword(s):  
Animal Studies ◽  
Data Extraction ◽  
Sodium Thiosulfate ◽  
Scientific Data ◽  
Limiting Factor ◽  
Factors Affecting ◽  
Biochemical Alterations ◽  
Medline Search ◽  
Cisplatin Nephrotoxicity ◽  
Manual Search

OBJECTIVE: To review recent advances in the understanding of the mechanisms of cisplatin nephrotoxicity. Factors affecting this toxicity and agents that may protect against it are discussed. DATA SOURCES: A MEDLINE search was used to identify pertinent literature including reviews. A manual search of bibliographies was performed to include all articles on the subject. STUDY SELECTION: All available data relating to the mechanisms, modifying factors, and management of cisplatin nephrotoxicity were assessed. DATA EXTRACTION: As limited human data are available, all animal studies were included. Articles with hypotheses or suggestions not backed by scientific data were excluded from review. DATA SYNTHESIS: Cisplatin is one of the most effective agents available for treating a variety of solid tumors. Nephrotoxicity is the dose-limiting factor for the use of this drug. Mechanisms for renal toxicity range from definitive histologic changes found in the proximal convoluted tubules to physiologic and biochemical alterations involving a decrease in mitochondrial respiratory function, enzymatic activity in the respiratory chain and glutathione peroxidase, and effects on cellular calcium homeostasis. Important factors related to nephrotoxicity include age, renal irradiation, and concurrent alcohol intake. Agents that appear promising in attenuating the nephrotoxic effects of cisplatin include loading with NaCl solution and/or mannitol, sodium thiosulfate, WR 2721, glutathione, probenecid, and many other compounds under active investigation. CONCLUSIONS: Cisplatin is a nephrotoxic drug; however, agents that may make cisplatin therapy more safe and rewarding will be available in the near future.

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