Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
EJNMMI Research
Published in: EJNMMI Research 1/2015

Open Access 01-12-2015 | Research Article

Imaging of reactive oxygen species using [3H]hydromethidine in mice with cisplatin-induced nephrotoxicity

Authors: Nozomi Takai, Kohji Abe, Misato Tonomura, Natsumi Imamoto, Kazumi Fukumoto, Miwa Ito, Sotaro Momosaki, Kae Fujisawa, Kenji Morimoto, Nobuo Takasu, Osamu Inoue

Published in: EJNMMI Research | Issue 1/2015

Login to get access

Abstract

Background

Reactive oxygen species (ROS) have been implicated in cisplatin-induced nephrotoxicity. The aim of this study was to investigate the potential of using [3H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([3H]hydromethidine) for ex vivo imaging of regional ROS overproduction in mouse kidney induced by cisplatin.

Methods

Male C57BL/6 J mice were intraperitoneally administered with a single dose of cisplatin (30 mg/kg). Renal function was assessed by measuring serum creatinine and blood urea nitrogen (BUN) levels and morphology by histological examination. Renal malondialdehyde levels were measured as a lipid peroxidation marker. Autoradiographic studies were performed with kidney sections from mice at 60 min after [3H]hydromethidine injection.

Results

Radioactivity accumulation after [3H]hydromethidine injection was observed in the renal corticomedullary area of cisplatin-treated mice and was attenuated by pretreatment with dimethylthiourea (DMTU), a hydroxyl radical scavenger. Cisplatin administration significantly elevated serum creatinine and BUN levels, caused renal tissue damage, and promoted renal lipid peroxidation. These changes were significantly suppressed by DMTU pretreatment.

Conclusions

The present study showed that [3H]hydromethidine was rapidly distributed to the kidney after its injection and trapped there in the presence of ROS such as hydroxyl radicals, suggesting that [3H]hydromethidine is useful for assessment of the renal ROS amount in cisplatin-induced nephrotoxicity.
Literature
1.
Dröge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002;82:47–95.PubMed
2.
Baliga R, Ueda N, Walker PD, Shah SV. Oxidant mechanisms in toxic acute renal failure. Drug Metab Rev. 1999;31:971–97.PubMedCrossRef
3.
Parra Cid T, Conejo García JR, Carballo Alvarez F, de Arriba G. Antioxidant nutrients protect against cyclosporine A nephrotoxicity. Toxicology. 2003;189:99–111.PubMedCrossRef
4.
Kohda Y, Gemba M. Cephaloridine induces translocation of protein kinase C delta into mitochondria and enhances mitochondrial generation of free radicals in the kidney cortex of rats causing renal dysfunction. J Pharmacol Sci. 2005;98:49–57.PubMedCrossRef
5.
Kadkhodaee M, Khastar H, Arab HA, Ghaznavi R, Zahmatkesh M, Mahdavi-Mazdeh M. Antioxidant vitamins preserve superoxide dismutase activities in gentamicin-induced nephrotoxicity. Transplant Proc. 2007;39:864–5.PubMedCrossRef
6.
Shackelford RE, Kaufmann WK, Paules RS. Oxidative stress and cell cycle checkpoint function. Free Radic Biol Med. 2000;28:1387–404.PubMedCrossRef
7.
Cuzzocrea S, Riley DP, Caputi AP, Salvemini D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev. 2001;53:135–59.PubMed
8.
Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of cisplatin nephrotoxicity. Toxins (Basel). 2010;2:2490–518.CrossRef
9.
Ramesh G, Reeves WB. p38 MAP kinase inhibition ameliorates cisplatin nephrotoxicity in mice. Am J Physiol Renal Physiol. 2005;289:F166–74.PubMedCrossRef
10.
Jiang M, Wei Q, Pabla N, Dong G, Wang CY, Yang T, et al. Effects of hydroxyl radical scavenging on cisplatin-induced p53 activation, tubular cell apoptosis and nephrotoxicity. Biochem Pharmacol. 2007;73:1499–510.PubMedCentralPubMedCrossRef
11.
Santos NA, Bezerra CS, Martins NM, Curti C, Bianchi ML, Santos AC. Hydroxyl radical scavenger ameliorates cisplatin-induced nephrotoxicity by preventing oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria. Cancer Chemother Pharmacol. 2008;61:145–55.PubMedCrossRef
12.
Tsuji T, Kato A, Yasuda H, Miyaji T, Luo J, Sakao Y, et al. The dimethylthiourea-induced attenuation of cisplatin nephrotoxicity is associated with the augmented induction of heat shock proteins. Toxicol Appl Pharmacol. 2009;234:202–8.PubMedCrossRef
13.
Kielland A, Blom T, Nandakumar KS, Holmdahl R, Blomhoff R, Carlsen H. In vivo imaging of reactive oxygen and nitrogen species in inflammation using the luminescent probe L-012. Free Radic Biol Med. 2009;47:760–6.PubMedCrossRef
14.
15.
Asghar MN, Emani R, Alam C, Helenius TO, Grönroos TJ, Sareila O, et al. In vivo imaging of reactive oxygen and nitrogen species in murine colitis. Inflamm Bowel Dis. 2014;20:1435–47.PubMedCrossRef
16.
Kundu K, Knight SF, Willett N, Lee S, Taylor WR, Murthy N. Hydrocyanines: a class of fluorescent sensors that can image reactive oxygen species in cell culture, tissue, and in vivo. Angew Chem Int Ed Engl. 2009;48:299–303.PubMedCrossRef
17.
Kundu K, Knight SF, Lee S, Taylor WR, Murthy N. A significant improvement of the efficacy of radical oxidant probes by the kinetic isotope effect. Angew Chem Int Ed Engl. 2010;49:6134–8.PubMedCentralPubMedCrossRef
18.
Bindokas VP, Kuznetsov A, Sreenan S, Polonsky KS, Roe MW, Philipson LH. Visualizing superoxide production in normal and diabetic rat islets of Langerhans. J Biol Chem. 2003;278:9796–801.PubMedCrossRef
19.
Hall DJ, Han SH, Chepetan A, Inui EG, Rogers M, Dugan LL. Dynamic optical imaging of metabolic and NADPH oxidase-derived superoxide in live mouse brain using fluorescence lifetime unmixing. J Cereb Blood Flow Metab. 2012;32:23–32.PubMedCentralPubMedCrossRef
20.
Takamiya M, Miyamoto Y, Yamashita T, Deguchi K, Ohta Y, Abe K. Strong neuroprotection with a novel platinum nanoparticle against ischemic stroke- and tissue plasminogen activator-related brain damages in mice. Neuroscience. 2012;221:47–55.PubMedCrossRef
21.
Sun L, Wolferts G, Veltkamp R. Oxygen therapy does not increase production and damage induced by reactive oxygen species in focal cerebral ischemia. Neurosci Lett. 2014;577:1–5.PubMedCrossRef
22.
Abe K, Takai N, Fukumoto K, Imamoto N, Tonomura M, Ito M, et al. In vivo imaging of reactive oxygen species in mouse brain by using [3H]hydromethidine as a potential radical trapping radiotracer. J Cereb Blood Flow Metab. 2014;34:1907–13.PubMedCrossRef
23.
Wei Q, Wang MH, Dong Z. Differential gender differences in ischemic and nephrotoxic acute renal failure. Am J Nephrol. 2005;25:491–9.PubMedCrossRef
24.
Domitrović R, Potočnjak I, Crnčević-Orlić Z, Škoda M. Nephroprotective activities of rosmarinic acid against cisplatin-induced kidney injury in mice. Food Chem Toxicol. 2014;66:321–8.PubMedCrossRef
25.
Gonzales-Vitale JC, Hayes DM, Cvitkovic E, Sternberg SS. The renal pathology in clinical trials of cis-platinum (II) diamminedichloride. Cancer. 1977;39:1362–71.PubMedCrossRef
26.
Arjumand W, Sultana S. Glycyrrhizic acid: a phytochemical with a protective role against cisplatin-induced genotoxicity and nephrotoxicity. Life Sci. 2011;89:422–9.PubMedCrossRef
27.
Wei J, Chen X, Li Q, Chen J, Khan N, Wang B, et al. ELR-CXC chemokine antagonism and cisplatin co-treatment additively reduce H22 hepatoma tumor progression and ameliorate cisplatin-induced nephrotoxicity. Oncol Rep. 2014;31:1599–604.PubMed
28.
Yao X, Panichpisal K, Kurtzman N, Nugent K. Cisplatin nephrotoxicity: a review. Am J Med Sci. 2007;334:115–24.PubMedCrossRef
29.
Pabla N, Murphy RF, Liu K, Dong Z. The copper transporter Ctr1 contributes to cisplatin uptake by renal tubular cells during cisplatin nephrotoxicity. Am J Physiol Renal Physiol. 2009;296:F505–11.PubMedCentralPubMedCrossRef
30.
Chu W, Chepetan A, Zhou D, Shoghi KI, Xu J, Dugan LL, et al. Development of a PET radiotracer for non-invasive imaging of the reactive oxygen species, superoxide, in vivo. Org Biomol Chem. 2014;12:4421–31.PubMedCentralPubMedCrossRef
31.
Carroll V, Michel BW, Blecha J, VanBrocklin H, Keshari K, Wilson D, et al. A boronate-caged [18F]FLT probe for hydrogen peroxide detection using positron emission tomography. J Am Chem Soc. 2014;136:14742–5.PubMedCrossRef
32.
Sugiyama A, Sun J, Nishinohara M, Fujita Y, Masuda A, Ochi T, et al. Expressions of lipid oxidation markers, N(ε)-hexanoyl lysine and acrolein in cisplatin-induced nephrotoxicity in rats. J Vet Med Sci. 2011;73:821–6.PubMedCrossRef
33.
Metadata
Title
Imaging of reactive oxygen species using [3H]hydromethidine in mice with cisplatin-induced nephrotoxicity
Authors
Nozomi Takai
Kohji Abe
Misato Tonomura
Natsumi Imamoto
Kazumi Fukumoto
Miwa Ito
Sotaro Momosaki
Kae Fujisawa
Kenji Morimoto
Nobuo Takasu
Osamu Inoue
Publication date
01-12-2015
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2015
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-015-0116-0

Other articles of this Issue 1/2015

EJNMMI Research 1/2015 Go to the issue

Original research

Radioiodinated PARP1 tracers for glioblastoma imaging

Original research

Evaluation of elastix-based propagated align algorithm for VOI- and voxel-based analysis of longitudinal 18F-FDG PET/CT data from patients with non-small cell lung cancer (NSCLC)

Short communication

[111In]PSMA-I&T: expanding the spectrum of PSMA-I&T applications towards SPECT and radioguided surgery

Original research

Reduced acquisition times in whole body bone scintigraphy using a noise-reducing Pixon®-algorithm—a qualitative evaluation study

Original research

Hybrid PET/optical imaging of integrin αVβ3 receptor expression using a 64Cu-labeled streptavidin/biotin-based dimeric RGD peptide

Original research

Molecular imaging of angiogenesis after myocardial infarction by 111In-DTPA-cNGR and 99mTc-sestamibi dual-isotope myocardial SPECT