The impact of the sepsis on female urogenital system: the role of pregabalin
The aim of the study was to investigate the oxidative damage and inflammatory effects of sepsis on the urogenital system in the Lipopolysaccharide (LPS)-induced sepsis model and ameliorating role of Pregabalin (PGB).
Twenty-four female Wistar Albino rats (12 months old) were divided into 3 groups as follows: Sepsis group (Group S) (5 mg/kg LPS, i.p, single dose); Sepsis+ PGB group (Group SP) (5 mg/kg LPS, i.p, single dose and 30 mg/kg PGB); Control group (Group C) (0.1 ml/oral and i.p. saline, single dose), 6 h after LPS administration, the animals were killed. Subsequently, analyses of urogenital tissue oxidant/antioxidant status, histopathological and immunohistochemical analyses were performed.
Total oxidative status (TOS) and oxidative stress index (OSI) values in the urogenital tissues were increased in Group S (Total anti-oxidative status (TAS) decreased) compared to the Control group (p < 0.05). PGB improved these values (p < 0.05). The immunohistochemical markers [Caspase-3, granulocyte colony-stimulating factor (G-CSF), interleukin-6 (IL-6), Serum Amyloid A (SAA) and inducible nitric oxide synthase (iNOS)] were significantly increased in Group S except for bladder (p < 0.001). Statistically significant immunohistochemical positiveness was found only for IL-6 in urinary bladder, though all the others values were negative. With the administration of PGB (Group SP), the expressions of these immunoreactions were markedly decreased (p < 0.001).
These findings demonstrated that sepsis caused oxidative stress and inflammation in the urogenital tissues. We have revealed that PGB ameliorated tissue damage caused by sepsis.
KeywordsUrogenital system Lps-induced rat sepsis Pregabalin
The authors thank the participants of this study.
GI contributed in the literature search, project development, manuscript writing/editing, data collection and interpretation, experimental rat study, rat killing and revised the article; SM contributed in biochemical analysis, statistical analysis, rat killing; OO contributed in histopathological and immunohistochemical analyses, management data analysis, and statistical analysis.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Conflict of interest
We declare that we have no conflict of interest with respect to the authorship and publication of this article.
- 3.Marshall JC, Vincent JL, Guyatt G, Angus DC, Abraham E, Bernard G, Bombardier C, Calandra T, Jørgensen HS, Sylvester R, Boers M (2005) Outcome measures for clinical research in sepsis: a report of the 2nd Cambridge Colloquium of the International Sepsis Forum. Crit Care Med 33(8):1708–1716. https://doi.org/10.1097/01.CCM.0000174478.70338.03 CrossRefPubMedGoogle Scholar
- 4.Tsiotou AG, Sakorafas GH, Anagnostopoulos G, Bramis J (2005) Septic shock; current pathogenetic concepts from a clinical perspective. Med Sci Monit 11(3):76–85Google Scholar
- 13.Celik M, Kose A, Kose D, Karakus E, Akpinar E, Calik M, Dostbil A, Calikoglu C, Aksoy M, Ozel L (2015) The double-edged sword:effects of pregabalin on experimentally induced sciatic nervetransection and crush injury in rats. Int J Neurosci 125(11):845–854. https://doi.org/10.3109/00207454.2014.978976 CrossRefPubMedGoogle Scholar
- 15.André V, Rigoulot MA, Koning E, Ferrandon A, Nehlig A (2003) Long term pregabalin treatment protects basal cortices and delays the occurrence of spontaneous seizures in the lithium-pilocarpine model in the rat. Epilepsia 44(7):893–903. https://doi.org/10.1046/j.1528-1157.2003.61802.x CrossRefGoogle Scholar
- 16.Song Y, Jun JH, Shin EJ, Kwak YL, Shin JS, Shim JK (2017) Effect of pregabalin administration upon reperfusion in a rat model of hyperglycemic stroke: mechanistic insights associated with high-mobility group box 1. PLoS One 12(2):e0171147. https://doi.org/10.1371/journal.pone.0171147 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Shamsi Meymandi M, Soltani Z, Sepehri G, Amiresmaili S, Farahani F, Moeini Aghtaei M (2018) Effects of pregabalin on brain edema, neurologic and histologic outcomes in experimental traumatic brain injury. Brain Res Bull 140:169–175. https://doi.org/10.1016/j.brainresbull.2018.05.001 CrossRefPubMedGoogle Scholar
- 22.Loutochin O, Al Afraa T, Campeau L, Mahfouz W, Elzayat E, Corcos J (2012) Effect of the anticonvulsant medications pregabalin and lamotrigine on urodynamic parameters in an animal model of neurogenic detrusor overactivity. Neurourol Urodyn 31(7):1197–1202. https://doi.org/10.1002/nau.21214 CrossRefPubMedGoogle Scholar
- 25.Asgari Z, Rouholamin S, Nataj M, Sepidarkish M, Hosseini R, Razavi M (2017) Dose ranging effects of pregabalin on pain in patients undergoing laparoscopic hysterectomy: a randomized, double blinded, placebo controlled, clinical trial. J Clin Anesth 38:13–17. https://doi.org/10.1016/j.jclinane.2017.01.015 CrossRefPubMedGoogle Scholar
- 26.Di Cesare Mannelli L, Maresca M, Micheli L, Farina C, Scherz MW, Ghelardini C (2017) A rat model of FOLFOX-induced neuropathy: effects of oral dimiracetam in comparison with duloxetine and pregabalin. Cancer Chemother Pharmacol 80(6):1091–1103. https://doi.org/10.1007/s00280-017-3449-8 CrossRefPubMedGoogle Scholar
- 27.Meymandi MS, Sepehri G, Abdolsamadi M, Shaabani M, Heravi G, Yazdanpanah O, Aghtaei MM (2017) The effects of co-administration of pregabalin and vitamin E on neuropathic pain induced by partial sciatic nerve ligation in male rats. Inflammopharmacology 25(2):237–246. https://doi.org/10.1007/s10787-017-0325-4 CrossRefPubMedGoogle Scholar
- 32.Lorente L, Martín MM, Pérez-Cejas A, González-Rivero AF, López RO, Ferreres J, Solé-Violán J, Labarta L, Díaz C, Palmero S, Jiménez A (2018) Sustained high serum caspase-3 concentrations and mortality in septic patients. Eur J Clin Microbiol Infect Dis 37(2):281–288. https://doi.org/10.1007/s10096-017-3129-y CrossRefPubMedGoogle Scholar