The Role of S-methylisothiourea Hemisulfate As Inducible Nitric Oxide Synthase Inhibitor Against Kidney Iron Deposition in Iron Overload Rats

Overview

Journal Adv Biomed Res

Specialty Biomedical Engineering

Date 2016 Jun 17

PMID 27308268

Citations 1

Authors

Maryam Maleki

Melika Samadi

Mehrangiz Khanmoradi

Mehdi Nematbakhsh

Ardeshir Talebi

Hamid Nasri

Affiliations

Soon will be listed here.

Abstract

Background: Iron dextran is in common use to maintain iron stores. However, it is potentially toxic and may lead to iron deposition (ID) and impair functions of organs. Iron overload can regulate the expression of inducible nitric oxide synthase (iNOS) in some cells that has an important role in tissue destruction. S-methylisothiourea hemisulfate (SMT) is a direct inhibitor of iNOS, and this study was designed to investigate the effect of SMT against kidney ID in iron overload rats.

Materials And Methods: 24 Wistar rats (male and female) were randomly assigned to two groups. Iron overloading was performed by iron dextran 100 mg/kg/day every other day for 2 weeks. In addition, during the study, groups 1 and 2 received vehicle and SMT (10 mg/kg, ip), respectively. Finally, blood samples were obtained, and the kidneys were prepared for histopathological procedures.

Results: SMT significantly reduced the serum levels of creatinine and blood urea nitrogen. However, SMT did not alter the serum levels of iron and nitrite, and the kidney tissue level of nitrite. Co-administration of SMT with iron dextran did not attenuate the ID in the kidney.

Conclusion: SMT, as a specific iNOS inhibitor, could not protect the kidney from ID while it attenuated the serum levels of kidney function biomarkers.

Citing Articles

Development of a mouse iron overload-induced liver injury model and evaluation of the beneficial effects of placenta extract on iron metabolism.

Yamauchi A, Kamiyoshi A, Sakurai T, Miyazaki H, Hirano E, Lim H Heliyon. 2019; 5(5):e01637.

PMID: 31193082 PMC: 6515419. DOI: 10.1016/j.heliyon.2019.e01637.

References

Lu N, Li X, Li J, Xu W, Li H, Gao Z . Nitrative and oxidative modifications of enolase are associated with iron in iron-overload rats and in vitro. J Biol Inorg Chem. 2010; 16(3):481-90. DOI: 10.1007/s00775-010-0747-6. View

Wen S, Huang T, Li G, Yamahara J, Roufogalis B, Li Y . Bromelain improves decrease in defecation in postoperative rats: modulation of colonic gene expression of inducible nitric oxide synthase. Life Sci. 2005; 78(9):995-1002. DOI: 10.1016/j.lfs.2005.06.007. View

Wildhirt S, Suzuki H, Horstman D, Weismuller S, Dudek R, Akiyama K . Selective modulation of inducible nitric oxide synthase isozyme in myocardial infarction. Circulation. 1997; 96(5):1616-23. DOI: 10.1161/01.cir.96.5.1616. View

Hou Y, Zhang S, Wang L, Li J, Qu G, He J . Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element. Gene. 2012; 511(2):398-403. DOI: 10.1016/j.gene.2012.09.060. View

Shiva S . Nitrite: A Physiological Store of Nitric Oxide and Modulator of Mitochondrial Function. Redox Biol. 2013; 1(1):40-44. PMC: 3661298. DOI: 10.1016/j.redox.2012.11.005. View

Metzger I, Sertorio J, Tanus-Santos J . Relationship between systemic nitric oxide metabolites and cyclic GMP in healthy male volunteers. Acta Physiol (Oxf). 2006; 188(2):123-7. DOI: 10.1111/j.1748-1716.2006.01612.x. View

Szabo C, Southan G, Thiemermann C . Beneficial effects and improved survival in rodent models of septic shock with S-methylisothiourea sulfate, a potent and selective inhibitor of inducible nitric oxide synthase. Proc Natl Acad Sci U S A. 1994; 91(26):12472-6. PMC: 45460. DOI: 10.1073/pnas.91.26.12472. View

Kelm M, Preik M, Strauer B . Serum nitrite sensitively reflects endothelial NO formation in human forearm vasculature: evidence for biochemical assessment of the endothelial L-arginine-NO pathway. Cardiovasc Res. 1999; 41(3):765-72. DOI: 10.1016/s0008-6363(98)00259-4. View

Prabhakar S, Zeballos G, Leonard C . Urea inhibits inducible nitric oxide synthase in macrophage cell line. Am J Physiol. 1998; 273(6):C1882-8. DOI: 10.1152/ajpcell.1997.273.6.C1882. View

10.

Pimkova K, Chrastinova L, Suttnar J, Stikarova J, Kotlin R, cermak J . Plasma levels of aminothiols, nitrite, nitrate, and malondialdehyde in myelodysplastic syndromes in the context of clinical outcomes and as a consequence of iron overload. Oxid Med Cell Longev. 2014; 2014:416028. PMC: 3942103. DOI: 10.1155/2014/416028. View

11.

Chen L, Hsu C, Wang J, Chen J, Chen S . Specific inhibition of iNOS decreases the intestinal mucosal peroxynitrite level and improves the barrier function after thermal injury. Burns. 1999; 24(8):699-705. DOI: 10.1016/s0305-4179(98)00114-4. View

12.

Tsai S, Hung L, Fu Y, Cheng H, Nien M, Liu H . Resveratrol neuroprotective effects during focal cerebral ischemia injury via nitric oxide mechanism in rats. J Vasc Surg. 2007; 46(2):346-53. DOI: 10.1016/j.jvs.2007.04.044. View

13.

Kolasa A, Marchlewicz M, Kurzawa R, Glabowski W, Trybek G, Wenda-Rozewicka L . The expression of inducible nitric oxide synthase (iNOS) in the testis and epididymis of rats with a dihydrotestosterone (DHT) deficiency. Cell Mol Biol Lett. 2009; 14(3):511-27. PMC: 6275914. DOI: 10.2478/s11658-009-0019-z. View

14.

Zhao T, Xi L, Chelliah J, Levasseur J, Kukreja R . Inducible nitric oxide synthase mediates delayed myocardial protection induced by activation of adenosine A(1) receptors: evidence from gene-knockout mice. Circulation. 2000; 102(8):902-7. DOI: 10.1161/01.cir.102.8.902. View

15.

Rusovici A, Ibrahim S, Sood S, Maher J, Gerula C, Kaluski E . Extensive myocardial iron deposition in a patient with hepatitis C. Tex Heart Inst J. 2012; 39(2):281-3. PMC: 3384049. View

16.

OBryan M, Schlatt S, Gerdprasert O, Phillips D, de Kretser D, Hedger M . Inducible nitric oxide synthase in the rat testis: evidence for potential roles in both normal function and inflammation-mediated infertility. Biol Reprod. 2000; 63(5):1285-93. DOI: 10.1095/biolreprod63.5.1285. View

17.

de Almeida R, de Sousa J, Ribeiro P, Silva S, Firmino M, de Oliveira P . Evaluation of the effects of S-methylisothiourea hemisulfate, an inducible nitric oxide synthase inhibitor, on the healing of colonic anastomosis in rats. Acta Cir Bras. 2012; 27(12):892-6. DOI: 10.1590/s0102-86502012001200011. View

18.

Gupta A, Sharma S, Chopra K . Reversal of iron-induced nephrotoxicity in rats by molsidomine, a nitric oxide donor. Food Chem Toxicol. 2007; 46(2):537-43. DOI: 10.1016/j.fct.2007.08.041. View

19.

Pechenik J, Cochrane D, Li W, West E, Pires A, Leppo M . Nitric oxide inhibits metamorphosis in larvae of Crepidula fornicata, the slippershell snail. Biol Bull. 2007; 213(2):160-71. DOI: 10.2307/25066632. View

20.

Schneider S, Bhatia K . Excess iron harms the brain: the syndromes of neurodegeneration with brain iron accumulation (NBIA). J Neural Transm (Vienna). 2012; 120(4):695-703. DOI: 10.1007/s00702-012-0922-8. View