Skip to main content

Effects of organoselenium compound 2-(5-selenocyanato-pentyl)-benzo[de]isoquinoline 1,3-dione on cisplatin induced nephrotoxicity and genotoxicity: an investigation of the influence of the compound on oxidative stress and antioxidant enzyme system

BioMetals volume 26, pages 61–73 (2013)Cite this article

Abstract

Cisplatin is one of the most active cytotoxic agents used in the treatment of cancer. However, cisplatin therapy is also associated with severe side effects like nephrotoxicity and genotoxicity. Free oxygen radicals are known to play a major role in cisplatin induced toxicities. Selenium is believed to be an important trace element and dietary antioxidant because of its ability to scavenge free oxygen radicals, thereby preventing cells from oxidative stress. The purpose of this study is to evaluate the protective role of a novel naphthalimide based organoselenium compound 2-(5-selenocyanato-pentyl)-benzo[de]isoquinoline 1,3-dione against cisplatin induced toxicities in Swiss albino mice. Cisplatin was administered intraperitoneally (5 mg/kg b.w.) and the organoselenium compound was given by oral gavages (3 mg/kg b.w.) in concomitant and pretreatment schedule. The results showed that the test compound substantially reduced cisplatin induced reactive oxygen species generation and lipid peroxidation in kidney as well as blood urea nitrogen and creatinine levels in serum. Treatment with organoselenium compound was also able to restore the renal antioxidant system by modulating the cisplatin induced depleted activities of glutathione S-transferase, thioredoxin reductase, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione level. In addition, the organoselenium compound could efficiently minimize cisplatin induced chromosomal aberrations in bone marrow cells and extent of DNA damage in lymphocytes. Furthermore, the chemoprotective efficacy of the compound against cisplatin induced toxicity was confirmed by histopathological evaluation. The results suggest that the organoselenium compound has the potential to protect against cisplatin induced nephrotoxicity and genotoxicity in part by scavenging reactive oxygen species and by up regulating the antioxidant enzyme system.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  • Allan C, Lacourciere G, Stadtman T (1999) Responsiveness of selenoproteins to dietary selenium. Annu Rev Nutr 19:1–16

    Article  CAS  PubMed  Google Scholar 

  • Antunes LMG, Darin DJC, Bianchi MD (2000a) Protective effect of vitamin C against cisplatin induced nephrotoxicity and lipid peroxidation in adult rats: a dose dependant study. Pharmacol Res 41:405–411

    Article  CAS  PubMed  Google Scholar 

  • Antunes LMG, Francescato HD, Darin DJC, Bianchi MD (2000b) Effects of selenium pretreatment on cisplatin induced chromosome aberrations on Wister rats. Teratog Carcinog Mutagen 20:341–348

    Article  CAS  PubMed  Google Scholar 

  • Baldew GS, van den Hamer CJ, Los G, Vermeulen NP, de Goeij JJ, McVie JG (1989) Selenium-induced protection against cis-diamminedichloroplatinum (II) nephrotoxicity in mice and rats. Cancer Res 49:3020–3023

    CAS  PubMed  Google Scholar 

  • Berry M, Banu L, Harney J, Larsen P (1993) Functional characterization of the eukaryotic SECIS elements which direct selenocysteine insertion at UGA codons. EMBO J 12:3315–3322

    CAS  PubMed  Google Scholar 

  • Biswas SJ, Pathak S, Khuda Bukhsh AR (2004) Assessment of the genotoxic and cytotoxic potential of an antiepileptic drug Phenobarbital, in mice: a time course study. Mutat Res 563:1–11

    Article  CAS  PubMed  Google Scholar 

  • Caffrey PB, Frenkel GD (2000) Selenium compounds prevent the induction of drug resistanceby cisplatin in human ovarian tumor xenografts in vivo. Cancer Chemother Pharmacol 46:74–78

    Article  CAS  PubMed  Google Scholar 

  • Carl Allinson MJ (1945) A specific enzymatic method for the determination of creatine and creatinine in blood. J Biol Chem 157:169–172

    Google Scholar 

  • Cathcart R, Schwiers E, Ames BN (1983) Detection of picomole levels of hydroperoxides using a fluorescent dichlorofluorescein assay. Anal Biochem 134:111–116

    Article  CAS  PubMed  Google Scholar 

  • Chaudiere J, Tappel AL (1984) Interaction of gold (I) with the active site of selenium-glutathione peroxidase. J Inorg Biochem 20:313–325

    Article  CAS  PubMed  Google Scholar 

  • Chen G, Hutter KJ, Zeller WJ (1995) Positive correlation between cellular glutathione and acquired cisplatin resistance in human ovarian cancer cells. Cell Biol Toxicol 11:273–281

    Article  CAS  PubMed  Google Scholar 

  • Cross HJ, Tilby M, Chipman JK, Ferry DR, Gescher A (1996) Effects of quercetin on the genotoxic potential of cisplatin. Int J Cancer 66:404–408

    Article  CAS  PubMed  Google Scholar 

  • Crow JP (1997) Dichlorodihydrofluorescein and dihydrorhodamine 123 are sensitive indicators of peroxynitrite in vitro: implications for intracellular measurement of reactive nitrogen and oxygen species. Nitric Oxide 1:145–157

    Article  CAS  PubMed  Google Scholar 

  • Davis CA, Nick HS, Agarwal A (2001) Manganese superoxide dismutase attenuates cisplatin induced renal injury: importance of superoxide. J Am Soc Nephrol 12:2683–2690

    CAS  PubMed  Google Scholar 

  • Douglas KT (1987) Mechanism of action of glutathione-dependent enzymes. Adv Enzymol Relat Areas Mol Biol 59:103–167

    CAS  PubMed  Google Scholar 

  • Endoh D, Okui T, Ozawa S, Yamato O, Kon Y, Arikawa J, Hayashi M (2002) Protective effect of a lignan-containing flaxseed extract against CCl4-induced hepatic injury. J Vet Med Sci 64:761–765

    Article  CAS  PubMed  Google Scholar 

  • Ganesan RW, Brian R (2004) Salicylate reduces cisplatin nephrotoxicity by inhibition of tumor necrosis factor. Kidney Int 65:490–498

    Article  Google Scholar 

  • Gordana B, Nada O, Fabijan K, Anica HK, Vesna B, Katarina S, Nikola B, Domagoj D (2011) The in vivo genotoxicity of cisplatin, isoflurane and halothane evaluated by alkaline comet assay in Swiss albino mice. J Appl Genetics 52:355–361

    Article  Google Scholar 

  • Griffith OW (1999) Biologic and pharmacologic regulation of mammalian glutathione synthesis. Free Radic Biol Med 27:922–935

    Article  CAS  PubMed  Google Scholar 

  • Habig WH, Pabst MJ, Jacoby WB (1974) Glutathione S-transferases, the first enzymatic step in marcapturic acid formation. J Biol Chem 249:7130–7139

    CAS  PubMed  Google Scholar 

  • Holben D, Smith A (1999) The diverse role of selenium within selenoproteins: a review. J Am Dietetic Assoc 99:836–843

    Article  CAS  Google Scholar 

  • Hrubisko M, Mc Gown AT, Fox BW (1993) The role of metallothionein, glutathione, glutathione S-transferases and DNA repair in resistance to platinum drugs in a series of L1210 cell lines made resistant to anticancer platinum agents. Biochem Pharmacol 45:253–256

    Article  CAS  PubMed  Google Scholar 

  • Huang Q, Dunn RT, Jayadev S, DiSorbo O, Pack FD, Farr SB, Stoll RE, Blanchard KT (2001) Assessment of cisplatin-induced nephrotoxocity by microarray technology. Toxicol Sci 63:196–207

    Article  CAS  PubMed  Google Scholar 

  • Ip C (1998) Lessons from basic research in selenium and cancer prevention. J Nutr 128:1845–1854

    CAS  PubMed  Google Scholar 

  • Joy J, Nair CKK (2008) Amelioration of cisplatin induced nephrotoxicity in Swiss albino mice by Rubia cordifolia extract. J Cancer Res Ther 4:111–115

    Article  PubMed  Google Scholar 

  • Leaver MJ, George SG (1998) A piscine glutathione S-transferase which efficiently conjugates the end-products of lipid peroxidation. Mar Environ Res 46:71–74

    Article  CAS  Google Scholar 

  • Lebwohl D, Canetta R (1998) Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. Eur J Cancer 34:1522–1534

    Article  CAS  PubMed  Google Scholar 

  • Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–276

    CAS  PubMed  Google Scholar 

  • Lu J, Wu DM, Hu B, Cheng W, Zheng YL, Zhang ZF, Ye Q, Fan SH, Shan Q, Wang YJ (2010) Chronic administration of troxerutin protects mouse brain against d-galactose-induced impairment of cholinergic system. Neurobiol Learn Mem 93:157–164

    Article  CAS  PubMed  Google Scholar 

  • Luck HA (1963) Spectrophotometric method for estimation of catalase. In: Bergmeyer HV (ed) Methods of enzymatic analysis. Academic Press, New York, pp 886–888

    Google Scholar 

  • Mansour HH, Hafez FH, Fahmy M (2006) Silymarin modulates cisplatin-induced oxidative stress and hepatotoxicity in rats. J Biochem Mol Biol 39:656–661

    Article  CAS  PubMed  Google Scholar 

  • Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in autooxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474

    Article  CAS  PubMed  Google Scholar 

  • Mather A, Roland D (1969) The automated thiosemicarbazidediacetyl monoxime method for plasma urea. Clin Chem 15:393–396

    CAS  PubMed  Google Scholar 

  • McCord JM, Fridovich I (1969) Superoxide dismutase: an enzymatic function for erythrocuprein (hemoprotein). J Biol Chem 244:6049–6055

    CAS  PubMed  Google Scholar 

  • Muller A, Cadenas E, Graf P, Sies H (1984) A novel biologically active seleno-organic compound-I. Biochem Pharmacol 33:3235–3239

    Article  CAS  PubMed  Google Scholar 

  • Mustacich D, Powis G (2000) Thioredoxin Reductase. Biochem J 346:1–8

    Article  CAS  PubMed  Google Scholar 

  • Narajji C, Karvekar MD, Das AK (2007) Biological importance of organoselenium compounds. Ind J Pharm Sci 69:344–351

    Article  CAS  Google Scholar 

  • Naziroglu M, Karaoglu A, Askoy AO (2004) Selenium and high dose vitamin E administration protects cisplatin-induced oxidative damage to renal, liver and lens tissues in rats. Toxicology 195:221–230

    Article  CAS  PubMed  Google Scholar 

  • Nguyena P, Awwada RT, Smarta DDK, Spitzb DR, Giusa D (2006) Thioredoxin reductase as a novel molecular target for cancer therapy. Cancer Lett 236:164–174

    Article  Google Scholar 

  • Nordberg J, Arner ESJ (2001) Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 31:1287–1312

    Article  CAS  PubMed  Google Scholar 

  • Okhawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Annal Biochem 95:351–358

    Article  Google Scholar 

  • Ozardali I, Bitiren M, Karakilcik AZ, Zerin M, Aksoy N, Musa D (2004) Effects of selenium on histopathological and enzymatic changes in experimental liver injury of rats. Exp Toxicol Pathol 56:59–64

    Article  CAS  PubMed  Google Scholar 

  • Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    CAS  PubMed  Google Scholar 

  • Sedlack J, Lindsay RN (1968) Estimation of total protein bound and non-protein sulfhydryl groups in tissue with ellman reagent. Annal Biochem 25:192–205

    Article  Google Scholar 

  • Sharma RP (1985) Interactions of cisplatin with cellular zinc and copper in liver and kidney tissues. Pharmacol Res Commun 17:197–206

    Article  CAS  PubMed  Google Scholar 

  • Shelly CLu (2009) Regulation of glutathione synthesis. Mol Aspec Med 30:42–59

    Article  Google Scholar 

  • Shinomol GK, Muralidhara (2007) Differential induction of oxidative impairments in brain regions of male mice following sub chronic consumption of Khesari dhal (Lathyrus sativus) and detoxified Khesari dhal. Neurotoxicology 28:798–806

    Article  CAS  PubMed  Google Scholar 

  • Sies H (1999) Glutathione and its cellular functions. Free Radic Biol Med 27:916–921

    Article  CAS  PubMed  Google Scholar 

  • Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191

    Article  CAS  PubMed  Google Scholar 

  • Singha Roy S, Ghosh P, Hossain SU, Chakraborty P, Biswas J, Mandal S, Bhattacharjee A, Bhattacharya S (2010) Naphthalimide based novel organoselenocyanates: finding less toxic forms of selenium that would retain protective efficacy. Bioorg Med Chem Lett 20:6951–6955

    Article  CAS  Google Scholar 

  • Sugie S, Tanaka T, El-Bayoumy K (2000) Chemoprevention of carcinogenesis by organoselenium compounds. J Health Sci 46:422–425

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Dr Jaydip Biswas, Director, Chittaranjan National Cancer Institute for his support in this study. Somnath Singha Roy gratefully acknowledges CSIR (01(2160)/07/EMR II) for fellowship.

Author information

Affiliations

  1. Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, West Bengal, India

    Prosenjit Ghosh, Somnath Singha Roy, Pramita Chakraborty & Sudin Bhattacharya

  2. Department of Pathology, Burdwan Medical College, Burdwan, West Bengal, India

    Sulekha Ghosh

Authors
  1. Prosenjit Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Somnath Singha Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pramita Chakraborty
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sulekha Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sudin Bhattacharya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sudin Bhattacharya.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ghosh, P., Roy, S.S., Chakraborty, P. et al. Effects of organoselenium compound 2-(5-selenocyanato-pentyl)-benzo[de]isoquinoline 1,3-dione on cisplatin induced nephrotoxicity and genotoxicity: an investigation of the influence of the compound on oxidative stress and antioxidant enzyme system. Biometals 26, 61–73 (2013). https://doi.org/10.1007/s10534-012-9594-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10534-012-9594-y

Keywords

  • Organoselenium
  • Cisplatin
  • Nephrotoxicity
  • Reactive oxygen species
  • Antioxidant enzyme system
  • DNA damage