Preconditioning with thyroid hormone (3,5,3-triiodothyronine) prevents renal ischemia-reperfusion injury in mice.
BACKGROUND
3,5,3-triiodothyronine (T3) was found to decrease ischemia-reperfusion (I/R) injury of liver and myocardium in animal models when preconditioned 48 hours in advance of the I/R injury. The purpose of this study was to evaluate the effects of T3 preconditioning on renal I/R injury with different time intervals and to determine the changes in antioxidants, apoptosis, and nitric oxide synthase (NOS) in each condition.


METHODS
In male C57BL/6 mice, renal I/R injury was induced by temporary ligation of the bilateral renal pedicles for 45 minutes followed by a reperfusion period for 24 hours. Preconditioning with intraperitoneal injection of T3 was performed 24 or 6 hours before or at the time of I/R injury.


RESULTS
From the histologic examination, tubular injury was decreased in mice preconditioned with T3 6 hours before I/R injury. The levels of proinflammatory cytokines were decreased with T3 preconditioning, either 6 hours or at the time of I/R injury. The levels of glutathione were increased in all treatment groups. Expressions of neuronal NOS were increased when preconditioned 6 hours before or at the time of I/R injury. The number of apoptotic tubular epithelial cell evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay was decreased when preconditioned immediately before I/R injury.


CONCLUSIONS
Preconditioning with T3 6 hours or immediately before I/R injury had a protective effect on renal I/R injury. The changes of NOS and antiapoptosis, other than well-known antioxidative properties, may play a role in the effect of short-term preconditioning.
Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
Suh Min
SM
Kim
Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
Si-Wha
SW
Kim
Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
Yoo-Jin
YJ
Jung
Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
Sang-Il
SI
Min
Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
Seung-Kee
SK
Min
Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
Sang Joon
SJ
Kim
Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: jwhamd@snu.ac.kr.
Jongwon
J
Ha
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004334:Drug Administration Schedule; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D019194:Ischemic Preconditioning / Q000379:methods*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020011:Protective Agents / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000517:prevention & control*; D016896:Treatment Outcome; D014284:Triiodothyronine / Q000627:therapeutic use*
D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D020011:Protective Agents; D014284:Triiodothyronine