Effects of sugammadex on immunoreactivity of calcineurin in rat testes cells after neuromuscular block: a pilot study
- 170 Downloads
Reversal of neuromuscular blockage induced by steroidal neuromuscular blocking agents such as rocuronium can be achieved using normal dose of sugammadex, which has been shown to be very effective for such reversal. In this study, we determined the effects of sugammadex on calcineurin immunoreactivity by examining the histopathological and histochemical structure of rat testis cells after neuromuscular blockage. Moreover, the regional distribution levels of calcineurin immunopositive testes cells were investigated. Eighteen adult male, Sprague–Dawley rats were divided into one control and two study groups. Study groups 1 and 2 rats received sugammadex at doses of 16 and 96 mg kg−1 i.v., respectively, after rocuronium treatment (mg kg−1 i.v.). The control group received intravenous 0.9% NaCl 1 ml. i.v without any drug. Our study demonstrates that sugammadex is safe and effective for reversal of rocuronium effects in rats, as well as in other animals and humans. Furthermore, histopathological examination indicates that high levels of sugammadex–rocuronium complexes accumulate a little in testis tissue. We found that rocuronium-sugammadex complexes were remained in circulation for a long time resulting in a decrease in interstitial space, testis size, germ cell numbers and Leydig cell numbers. Calcineurin immunoreactivity was higher in the experimental groups than the control group due to increase of calcium level. The results suggest that sugammadex–rocuronium complexes are cause histopathological and immunohistochemical changes in testis interstitial tissues, as well as changes in sperm density and germ cell number.
KeywordsSugammadex Rocuronium Testis Calcineurin Rat
The authors declare that they have no conflict of interest. This work was supported by all authors with no external funding from a government agency or company. The animals, materials and drugs were provided by the first author as research fund from his institution (Medical Faculty of Rize University, Department of Histology and Embryology).
- Adam JM, Bennett DJ, Bom A, Clark JK, Feilden H, Hutchinson EJ, Palin M, Prosser A, Rees DC, Rosair GM, Stevenson D, Tarver GJ, Zhang MQ (2002) Cyclodextrinderived host molecules as reversal agents for the neuromuscular blocker rocuronium bromide: synthesis and structure-activity relationships. J Med Chem 45:1806–1816. doi: 10.1021/jm011107f PubMedCrossRefGoogle Scholar
- Baldo BA, McDonnell NJ, Pham NH (2011) Drug-specific cyclodextrins with emphasis on sugammadex, the neuromuscular blocker rocuronium and perioperative anaphylaxis: implications for drug allergy. Clin Exp Allergy doi: 10.1111/j.1365-2222.2011.03805.x. [Epub ahead of print]
- Bancroft JD, Stevens A (1996) Theory and practice of histological techniques, 4th edn. Churchill-Livingstone, London, pp 42–165Google Scholar
- Klee CB, Draetta GF, Hubbard MJ (1988) Calcineurin. Adv Enzym Relat Areas Mol Biol 61:149–200Google Scholar
- Moriya M, Fujinaga K, Yazawa M, Katagiri C (1995) Immunohistochemical localization of the calcium/calmodulin-dependent protein phosphatase, calcineurin, in the mouse testis: its unique accumulation in spermatid nuclei. Cell Tissue Res 281(2):273–281. doi: 10.1007/BF00583396 PubMedCrossRefGoogle Scholar
- Peeters PA, van den Heuvel MW, van Heumen E, Passier PC, Smeets JM, van Iersel T, Zwiers A (2010) Safety, tolerability and pharmacokinetics of sugammadex using single high doses (up to 96 mg/kg) in healthy adult subjects: a randomized, double-blind, crossover, placebo-controlled, single-centre study. Clin Drug Investig 30(12):867–874. doi: 10.2165/11538920-000000000-00000 PubMedGoogle Scholar
- Sorgenfrei IF, Norrild K, Larsen PB, Stensballe J, Østergaard D, Prins ME, Viby-Mogensen J (2006) Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study. Anesthesıology 104:667–674. doi: 10.1097/00000542-200604000-00009 PubMedCrossRefGoogle Scholar
- Yamashita M, Katsumata M, Iwashima M, Kimura M, Shimizu C, Kamata T, Shin T, Seki N, Suzuki S, Taniguchi M, Nakayama T (2000) T cell receptor-induced calcineurin activation regulates T helper type 2 cell development by modifying the interleukin 4 receptor signaling complex. J Exp Med 191(11):1869–1879. doi: 10.1084/jem.191.11.1869 PubMedCrossRefGoogle Scholar