Effects of Pregabalin on Kidney Tissue in Spinal Cord Ischemia Reperfusion Injured Rats

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Emine Ünal Ceran
Nurten İnan
Ayşegül Küçük
Abdullah Özer
Ali Doğan Dursun
Murat Tosun
Mustafa Arslan


Objectives: The purpose of this study was to investigate the possible protective effects of low and high dose pregabalin that was administered in rat in a spinal cord ischemia-reperfusion (I/R) study model.
Material and Method: We used 24 Wistar albino rats as subjects in our study. They were divided into 4 groups; randomized Control (C group), I/R (I/R group), I/R-low dose (30 mg/kg) pregabalin (I/R-LP group) and I/R-high dose (200 mg/kg) pregabalin (I/R-HP group). All groups have undergone a laparotomy intervention under anesthesia. In I/R group, a cross clamp was placed in the abdominal aorta just after the laparotomy for 120 minutes (to cause spinal cord ischemia injury) and then reperfusion was achieved by opening the vascular clamp. At the end of the study, lung tissue was obtained for determining total oxidant status (TOS) and total antioxidant status (TAS) levels, histochemical and immunohistochemical determination.
Results: Total Oxidative Status (TOS) enzyme activity was significantly higher in I/R group when compared to the control, I/R-LP and I/R-HP groups. Likewise, Total Antioxidant Status (TAS) enzyme activity was remarkably higher in I/R group when compared with the C, I/R-LP and I/R-HP groups. VEGF staining has yielded no expression in renal tissues. In microscopical analysis of the tissue slides which were immunohistochemically stained with p53 antibody, some crucial findings have been established as follows: As p53-expressing cells were not detected in the control group, the presence of p53-expressing cells were clearly identified at different intensities in several bowman capsules in the I/R group. However, no expression was detected in general tubules. Interestingly, p53 expression levels were prominently lower in low-dose pregabalin given group and considerably higher in the 200 mg/kg pregabalin administered group, which was more pronounced than the I/R group.
Conclusion: Results established from the current study suggest that pregabalin given at different doses may have a partial protective effect in kidney tissues of rats undergone experimental spinal cord IR injury.

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Kazanci B, Ozdogan S, Kahveci R, Gokce EC, Yigitkanli K, Gokce A, et al. Neuroprotective Effects of Pregabalin Against Spinal Cord Ischemia-Reperfusion Injury in Rats. Turk Neurosurg 2017; 27:952-61.

Nigwekar SU, Kandula P, Hix JK, Thakar CV. Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis of randomized and observational studies. Am J Kidney Dis 2009; 54: 413-23.

Homer-Vanniasinkam S, Crinnion JN, Gough MJ. Post-ischaemic organ dysfunction: a review. Eur J Vasc Endovasc Surg 1997; 14: 195–203.

Martin L, Rabasseda X, Leeson P, Castaner J. Pregabalin. Drugs of the Future 1999; 24: 862–70.

Ha K, Kim Y, Rhyu K, Kwon S. Pregabalin as a neuroprotector after spinal cord injury in rats. Eur J Spine 2008; 17: 864-72

Jiang G, LiuII X, Wang M, Chen H, Chen Z, Qiu T. Oxymatrine ameliorates renal ischemia-reperfusion injury from oxidative stress through Nrf2/HO-1 pathway. Acta Cir Bras 2015; 30: 422-9.

Khajuria A, Tay C, Shi J, Zhao H, Ma D. Anesthetics attenuate ischemiae reperfusion induced renal injury: Effects and mechanisms. Acta Anaesthesiol Taiwan 2014; 52: 176-84.

Wan X, Hou LJ, Zhang LY, Huang WJ, Liu L, Zhang Q, et al. IKKα is involved in kidney recovery and regeneration ofacute ischemia/reperfusion injury in mice through IL-10-producing regulatory T cells. Dis Model Mech 2015; 8: 733-42.

Kiriş İ, Okutan H, Savaş Ç, Yönden Z, Delibaş N. Deneysel Aortik İskemi-Reperfüzyon modelinde renal hasara gadolinyum klorürün etkisi. Turkish J Vasc Surg 2005; 14: 13-8.

Brodie MJ. Pregabalin as adjunctive therapy for partial seizures. Epilepsia 2004; 45(Suppl 6): 19-27.

Partridge BJ, Chaplan SR, Sakamoto E, Yaksh TL. Characterization of the effects of gabapentin and 3-isobutyl-aminobutyric acid on substance P-induced thermal hyperalgesia. Anesthesiology 1998; 88: 196-205.

Ha KY, Carragee E, Cheng I, Kwon SE, Kim YH. Pregabalin as a Neuroprotector after Spinal Cord Injury in Rats: Biochemical Analysis and Effect on Glial Cells. J Korean Med Sci 2011; 26: 404-11.

Li M, Ona VO, Chen M, Kaul M, Tenneti L, Zhang X, et al. Functional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spinal cord injury. Neuroscience 2000; 99: 333-42.

Kim YK, Leem JG, Sim JY, Jeong SM, Joung KW. The effects of gabapentin pretreatment on brain injury induced by focal cerebral ischemia/reperfusion in the rat. Korean J Anesthesiol 2010;58:184-90.

Celik M, Kose A, Kose D, Karakus E, Akpinar E, Calik M, et al. The double edge sword: effects of pregabalin on experimentally induced sciatic nerve transection and crush injury in rats. Int J Neurosci 2015;125(11):845-54.

Calikoglu C, Aytekin H, Akgul O, Akgul MH, Gezen AF, Akyuz F, et al. Effect of Pregabalin in Preventing Secondary Damage in Traumatic Brain Injury: An Experimental Study. Med Sci Monit 2015; 21:813-20.

Wu JQ, Kosten TR, Zhang XY. Free radicals, antioxidant defense systems, and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2013;46:200-6.

Aşcı S, Demirci S, Aşcı H, Doğuç DK, Onaran İ. Neuroprotective Effects of Pregabalin on Cerebral Ischemia and Reperfusion. Balkan Med J 2016; 33:221-7.

Reddy VD, Padmavathi P, Kavitha G, Saradamma B, Varadacharyulu N. Alcohol-induced oxidative/nitrosative stress alters brain mitochondrial membrane properties. Mol Cell Biochem 2013;375:39-47.

Ozerol E, Bilgic S, Iraz M, Cigli A, Ilhan A, Akyol O. The protective effect of erdosteine on short-term global brain ischemia/ reperfusion injury in rats. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:20-4.

Tarpey MM, Wink DA, Grisham MB. Methods for detection of reactive metabolites of oxygen and nitrogen: in vitro and in vivo considerations. Am J Physiol Regul Integr Comp Physiol 2004; 286:R431-44.

Uzar E, Acar A, Fırat U, Evliyaoğlu O, Alp H, Tüfek A, et al. Protective Effect of Caffeic Acid Phenethyl Ester in Rat Cerebral Ischemia/Reperfusion Damage. Turk Norol Derg 2011;17:131-6.

Joyce M, Kelly C, Winter D, Chen G, Leahy A, BouchierHayes D. Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, attenuates renal injury in an experimental model of ischemia-reperfusion. J Surg Res 2001; 101:79-84