Volume 27, Issue 3 (September 2023)                   Physiol Pharmacol 2023, 27(3): 254-260 | Back to browse issues page

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Namavar M, talebianpoor M S, Nazari S, Mirkhani H. The effect of tempol, a potent synthetic antioxidant, on the limb teratogenicity in an experimental model of preeclampsia in rats. Physiol Pharmacol 2023; 27 (3) :254-260
URL: http://ppj.phypha.ir/article-1-1856-en.html
The effect of tempol, a potent synthetic antioxidant, on the limb teratogenicity in an experimental model of preeclampsia in rats
Mohammadreza Namavar , Mohammad sharif Talebianpoor , Somayeh Nazari , Hossein Mirkhani
Abstract:   (1305 Views)

Introduction: Preeclampsia is the principal cause of maternal morbidity and is characterized by hypertension, proteinuria, and edema. It is believed that oxidative stress plays an essential role in the pathophysiology of preeclampsia. This study was conducted to determine the effect of tempol on fetal limb hemorrhage, malformations, and oxidative stress in an N-nitro-L-arginine methyl ester (L-NAME)-induced preeclamptic rat model.
Methods: To induce preeclampsia, L-NAME (50 mg/kg/day, oral) was administered from day 11 of pregnancy to day 22. Four preeclamptic groups received L-NAME alone, L-NAME+tempol (20, 60, 180 mg/kg/day; L-NAME, L-T20, L-T60, L-T180 groups, respectively). The control group (normal pregnant) received only tap water, and the T60 group received tempol (60 mg/Kg) alone (without L-NAME). The concentration of 8-isoprostane in plasma and placenta, number and weight of the fetuses, and the limb defects were measured on the 22nd day of the pregnancy.
Results: L-NAME administration caused placental oxidative stress, limb defects and hemorrhage, and low fetal weight. Administration of tempol at 20 and 60 mg/kg/day reduced limb defects (10.5 and 7.2 percent versus 24.7 percent) and limb hemorrhage (14.5 and 9.5 percent versus 23 percent) induced by L-NAME. After administration of tempol (20 and 60 mg/kg), fetal weight increased (5.14±0.08 and 5.44±0.15 versus 4.27± 0.11 g). Administration of tempol at the high dose (180 mg/kg/day) did not produce any significant effects on the measured parameters.
Conclusion: Tempol with certain doses improves fetal outcomes in an experimental rat model of preeclampsia. These may be the results of its antioxidant action.

Keywords: Limb malformation, L-NAME, Oxidative stress, Preeclampsia, Tempol
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Type of Manuscript: Experimental research article | Subject: Pharmacokinetics/Dynamics
References
1. Altoama K, Mallem MY, Thorin C, Betti E, Desfontis JC. Effect of nebivolol treatment during pregnancy on the intrauterine fetal growth, mortality and pup postnatal development in the l-NAME-induced hypertensive rats. Eur J Pharmacol 2016; 791: 465-72. [DOI:10.1016/j.ejphar.2016.09.028]
2. Amaral TA, Ognibene DT, Carvalho LC, Rocha APM, Costa CA, Moura RS, Resende AC. Differential responses of mesenteric arterial bed to vasoactive substances in L-NAME-induced preeclampsia: Role of oxidative stress and endothelial dysfunction. Clin Exp Hypertens 2018; 40: 126-35. [DOI:10.1080/10641963.2017.1339073]
3. Ardanaz NBW, Pagano PJ. Distinct hydrogen peroxide-induced constriction in multiple mouse arteries: potential influence of vascular polarization. Pharmacol Rep 2008; 60: 61-7.
4. Beckman JS KW. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol; 1996: 271, C1424-37. [DOI:10.1152/ajpcell.1996.271.5.C1424]
5. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-54. [DOI:10.1016/0003-2697(76)90527-3]
6. Burton GJ, Jauniaux E. Placental oxidative stress: from miscarriage to preeclampsia. JSGI 2004;11: 342-52. [DOI:10.1016/j.jsgi.2004.03.003]
7. Cushen SC, Goulopoulou S. New models of pregnancy-associated hypertension. Am J Hypertens 2017; 30: 1053-62. [DOI:10.1093/ajh/hpx063]
8. Fantel A, Stamps L, Tran T, Mackler B, Person R, Nekahi N. Role of free radicals in the limb teratogenicity of L-NAME (NG-nitro-L-arginine methyl ester): a new mechanistic model of vascular disruption. Teratology 1999; 60: 151-60. [DOI:10.1002/(SICI)1096-9926(199909)60:3%3C151::AID-TERA11%3E3.0.CO;2-E]
9. Fantel AGPR. Further evidence for the role of free radicals in the limb teratogenicity of L-NAME. Teratology 2002; 66: 24-32. [DOI:10.1002/tera.10047]
10. García-Redondo ABBA, Beltrán AE, Alonso MJ, Simonsen U, Salaices M. Hypertension increases contractile responses to hydrogen peroxide in resistance arteries through increased thromboxane A2, Ca2+, and superoxide anion levels. J Pharmacol Exp Ther 2009; 328: 19-27. [DOI:10.1124/jpet.108.144295]
11. Gregg AR, Schauer A, Shi O, Liu Z, Lee CG, O’Brien WE. Limb reduction defects in endothelial nitric oxide synthase-deficient mice Am J Physiol Heart Circ Physiol 1998; 275: H2319-24. [DOI:10.1152/ajpheart.1998.275.6.H2319]
12. Gupta S, Agarwal A, Sharma RK. The role of placental oxidative stress and lipid peroxidation in preeclampsia. Obstet Gynecol Surv 2005; 60: 807-16. [DOI:10.1097/01.ogx.0000193879.79268.59]
13. Helmbrecht GD, Farhat MY, Lochbaum L, Brown HE, Yadgarova KT, Eglinton GS, Ramwell PW. L-arginine reverses the adverse pregnancy changes induced by nitric oxide synthase inhibition in the rat. Am J Obstet Gynecol 1996; 175: 800-5. [DOI:10.1016/S0002-9378(96)80002-0]
14. Makris SL, Solomon HM, Clark R, Shiota K, Barbellion S, Buschmann J, Hazelden KP. Terminology of developmental abnormalities in common laboratory mammals (version 2). Congenit Anom 2009; 49: 123-246. [DOI:10.1111/j.1741-4520.2009.00239.x]
15. Noris MPN, Remuzzi G. Mechanisms of disease: Pre-eclampsia. Nat Clin Pract Nephrol 2005: 1: 98-114. [DOI:10.1038/ncpneph0035]
16. Ornaghi S, Hsieh LS, Bordey A, Vergani P, Paidas MJ, van den Pol AN. Valnoctamide inhibits cytomegalovirus infection in developing brain and attenuates neurobehavioral dysfunctions and brain abnormalities J Neurosci 2017; 37: 6877-93. [DOI:10.1523/JNEUROSCI.0970-17.2017]
17. Podjarny EBC, Losonczy G. Animal models of preeclampsia. Semin Perinatol 1999; 23: 2-13. [DOI:10.1016/S0146-0005(99)80055-X]
18. Podjarny E, Benchetrit S, Katz B, Green J, Bernheim J. Effect of methyldopa on renal function in rats with L-NAME-induced hypertension in pregnancy. Nephron 2001;88: 354-59. [DOI:10.1159/000046020]
19. Preti SC, Da Cunha V, Vassallo DV, Stefanon I. The superoxide dismutase mimetic, tempol, reduces the bioavailability of nitric oxide and does not alter l-name-induced hypertension in rats. Basic Clin Pharmacol Toxicol 2005; 97: 29-34. [DOI:10.1111/j.1742-7843.2005.pto_97105.x]
20. Rafikova OSE, Tofovic SP. Renal and metabolic effects of tempol in obese ZSF1 rats--distinct role for superoxide and hydrogen peroxide in diabetic renal injury. Metabolism 2008; 57: 1434-44. [DOI:10.1016/j.metabol.2008.05.014]
21. Ramos JGL, Sass N, Costa, SHM. Preeclampsia. Rev Bras Ginecol Obstet 2017; 39: 496-512. [DOI:10.1055/s-0037-1604471]
22. Roggensack AM, Zhang Y, Davidge ST. Evidence for peroxynitrite formation in the vasculature of women with preeclampsia. Hypertension 1999; 33: 83-89. [DOI:10.1161/01.HYP.33.1.83]
23. Ryu SKR, Samuni A, Ornoy A. Nitroxide radicals protect cultured rat embryos and yolk sacs from diabetic-induced damage. Birth Defects Res A Clin Mol Teratol 2007; 79: 604-11. [DOI:10.1002/bdra.20383]
24. Sedeek M, Gilbert JS, LaMarca BB, Sholook M, Chandler DL, Wang Y, Granger JP. Role of reactive oxygen species in hypertension produced by reduced uterine perfusion in pregnant rats. Am J Hypertens 2008; 21: 1152-56. [DOI:10.1038/ajh.2008.239]
25. Talebianpoor MS, Mirkhani H.. The effect of tempol administration on the aortic contractile responses in rat preeclampsia model. ISRN pharmacol 2012; 2012. [DOI:10.5402/2012/187208]
26. Talebianpoor MS, Owji SM, Goharinia M, Mirkhani H. Effect of tempol, a synthetic antioxidant, on renal complications of L-NAME induced preeclampsia in rat. Physiol Pharmacol 2017; 21: 241-50.
27. Talebianpoor MS, Delaviz H, Rafei R, Mohannadi B, Sadeghi H, Mohammadi J, Rad P. Resveratrol attenuates fetal limb malformation and cardiac hypertrophy after preeclampsia induced by L-NAME in pregnant rats. J Pharm Sci Res 2018; 10: 361-4.
28. Tanir HM ST, Inal M Akyuz F, Uzuner K, Sivri E. Effect of quercetine and glutathione on the level of superoxide dismutase, catalase, malonyldialdehyde, blood pressure and neonatal outcome in a rat model of pre-eclampsia induced by NG-nitro-L-arginine-methyl ester. Eur J Obstet Gynecol Reprod Biol 2005; 118: 190-5. [DOI:10.1016/j.ejogrb.2004.04.033]
29. Tenório MB, Ferreira RC, Moura FA, Bueno NB, de Oliveira ACM, Goulart MOF. Cross-Talk between Oxidative Stress and Inflammation in Preeclampsia. Oxid Med Cell Longev, 2019; 8238727. [DOI:10.1155/2019/8238727]
30. Tiboni GM GF, Di Giulio C. The nitric oxide synthesis inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) causes limb defects in mouse fetuses: protective effect of acute hyperoxia. Pediatr Res 2003; 54: 69-76. [DOI:10.1203/01.PDR.0000069840.78984.76]
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