Hyperbaric Oxygen Therapy Suppresses Apoptosis and Promotes Renal Tubular Regeneration After Renal Ischemia/Reperfusion Injury in Rats
Heihachi Migita, Shigenori Yoshitake, Yoshihiro Tange, Narantsog Choijookhuu, Yoshitaka Hishikawa, Heihachi Migita, Shigenori Yoshitake, Yoshihiro Tange, Narantsog Choijookhuu, Yoshitaka Hishikawa
Abstract
Background: Renal ischemia/reperfusion (I/R) injury remains a major cause of acute kidney injury (AKI), in addition to I/R injury-induced tissue inflammation, necrosis and apoptosis. Hyperbaric oxygen therapy (HBO) is defined as a treatment in which a patient is intermittently exposed to 100% oxygen pressurized to a pressure above sea level (> 2.0 atmospheres absolute (ATA), 1.0 ATA = 760 mmHg). It has been used in a number of medical conditions with a proven efficacy in a limited number of disorders. However, the effects of HBO therapy on apoptosis and proliferative activity after I/R injury have not been fully understood.
Objectives: We studied the possible beneficial effects of HBO therapy on apoptosis and tubular cell regeneration after renal I/R injury in rats.
Materials and methods: Sprague-Dawley (SD) rats were randomized into three groups: Sham (Sham-operated rats); I/R (animals submitted to I/R); and I/R + HBO (I/R rats exposed to HBO). Tubular cell apoptosis was confirmed by DNA laddering and the terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL) assay. Cellular proliferation activity was determined using the anti-Ki-67 antibody.
Results: A significant decrease in apoptotic cells and increase in proliferative reaction were observed in the I/R + HBO group compared to the I/R group.
Conclusions: We demonstrated that HBO suppressed apoptosis, which caused inflammation after renal I/R, and promoted tubular cell regeneration. HBO has protective effects against AKI caused by renal I/R through the inhibition of apoptosis.
Keywords: Apoptosis; Hyperbaric Oxygen Therapy; Ischemia/Reperfusion Injury; Rats.
Figures
References
- Sharples EJ, Patel N, Brown P, Stewart K, Mota-Philipe H, Sheaff M, et al. Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion. J Am Soc Nephrol. 2004;15(8):2115–24. doi: 10.1097/01.ASN.0000135059.67385.5D.
- Daemen MA, van 't Veer C, Denecker G, Heemskerk VH, Wolfs TG, Clauss M, et al. Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation. J Clin Invest. 1999;104(5):541–9. doi: 10.1172/JCI6974.
- Lieberthal W, Triaca V, Koh JS, Pagano PJ, Levine JS. Role of superoxide in apoptosis induced by growth factor withdrawal. Am J Physiol. 1998;275(5 Pt 2):F691–702.
- Wen X, Murugan R, Peng Z, Kellum JA. Pathophysiology of acute kidney injury: a new perspective. Contrib Nephrol. 2010;165:39–45. doi: 10.1159/000313743.
- Rubinstein I, Abassi Z, Milman F, Ovcharenko E, Coleman R, Winaver J, et al. Hyperbaric oxygen treatment improves GFR in rats with ischaemia/reperfusion renal injury: a possible role for the antioxidant/oxidant balance in the ischaemic kidney. Nephrol Dial Transplant. 2009;24(2):428–36. doi: 10.1093/ndt/gfn511.
- Tibbles PM, Edelsberg JS. Hyperbaric-oxygen therapy. N Engl J Med. 1996;334(25):1642–8. doi: 10.1056/NEJM199606203342506.
- Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992;119(3):493–501.
- Hishikawa Y, Tamaru N, Ejima K, Hayashi T, Koji T. Expression of keratinocyte growth factor and its receptor in human breast cancer: its inhibitory role in the induction of apoptosis possibly through the overexpression of Bcl-2. Arch Histol Cytol. 2004;67(5):455–64.
- Carrera Baltuylle B, Carrera Gutierrez J. [Apropos of 2 cases of giant inguinal hernia]. Rev Esp Enferm Apar Dig. 1978;54(2):197–202.
- Choijookhuu N, Hino S, Oo PS, Batmunkh B, Mohmand NA, Kyaw MT, et al. Ontogenetic changes in the expression of estrogen receptor beta in mouse duodenal epithelium. Clin Res Hepatol Gastroenterol. 2015;39(4):499–507. doi: 10.1016/j.clinre.2015.01.004.
- Brown DC, Gatter KC. Monoclonal antibody Ki-67: its use in histopathology. Histopathol J. 1990;17(6):489–503. doi: 10.1111/j.1365-2559.1990.tb00788.x.
- Weight SC, Bell PRF, Nicholson ML. Renal ischaemia-reperfusion injury. British J Surg. 1996;83(2):162–70. doi: 10.1002/bjs.1800830206.
- Solmazgul E, Uzun G, Cermik H, Atasoyu EM, Aydinoz S, Yildiz S. Hyperbaric oxygen therapy attenuates renal ischemia/reperfusion injury in rats. Urol Int. 2007;78(1):82–5. doi: 10.1159/000096941.
- Ramalho RJ, de Oliveira PS, Cavaglieri RC, Silva C, Medeiros PR, Filho DM, et al. Hyperbaric oxygen therapy induces kidney protection in an ischemia/reperfusion model in rats. Transplant Proc. 2012;44(8):2333–6. doi: 10.1016/j.transproceed.2012.07.020.
- Allen J, Winterford C, Axelsen RA, Gobe GC. Effects of hypoxia on morphological and biochemical characteristics of renal epithelial cell and tubule cultures. Ren Fail. 1992;14(4):453–60.
- Schumer M, Colombel MC, Sawczuk IS, Gobe G, Connor J, O'Toole KM, et al. Morphologic, biochemical, and molecular evidence of apoptosis during the reperfusion phase after brief periods of renal ischemia. Am J Pathol. 1992;140(4):831–8.
- Kantari C, Walczak H. Caspase-8 and bid: caught in the act between death receptors and mitochondria. Biochim Biophys Acta. 2011;1813(4):558–63. doi: 10.1016/j.bbamcr.2011.01.026.
- Kaufmann SH, Desnoyers S, Ottaviano Y, Davidson NE, Poirier GG. Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. Cancer Res. 1993;53(17):3976–85.
- Kreisberg JI, Bulger RE, Trump BF, Nagle RB. Effects of transient hypotension on the structure and function of rat kidney. Virchows Arch B Cell Pathol. 1976;22(2):121–33.
- Wang W, Reeves WB, Pays L, Mehlen P, Ramesh G. Netrin-1 overexpression protects kidney from ischemia reperfusion injury by suppressing apoptosis. Am J Pathol. 2009;175(3):1010–8. doi: 10.2353/ajpath.2009.090224.
Source: PubMed