1. 5-Aminolevulinic acid combined with ferrous iron induces carbon monoxide generation in mouse kidneys and protects from renal ischemia-reperfusion injury
- Author
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Yuya Kitajima, Qiang Ding, Tohru Tanaka, Hidenori Ito, Jiangang Hou, Kiwamu Takahashi, Fuminori Abe, Masayuki Fujino, Xiao-Kang Li, and Songjie Cai
- Subjects
Male ,Physiology ,Drug Evaluation, Preclinical ,Pharmacology ,urologic and male genital diseases ,medicine.disease_cause ,Ferrous ,Hemeoxygenase 1 ,chemistry.chemical_compound ,Mice ,Heme synthesis ,medicine ,Animals ,Ferrous Compounds ,RNA, Messenger ,Renal ischemia reperfusion ,Kidney ,Carbon Monoxide ,Mice, Inbred BALB C ,Cell Death ,Aminolevulinic Acid ,Acute Kidney Injury ,Oxidative Stress ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Reperfusion Injury ,Drug Therapy, Combination ,Oxidative stress ,Carbon monoxide - Abstract
Renal ischemia reperfusion injury (IRI) is a major factor responsible for acute renal failure. An intermediate in heme synthesis, 5-aminolevulinic acid (5-ALA) is fundamental in aerobic energy metabolism. Heme oxygenase (HO)-1 cleaves heme to form biliverdin, carbon monoxide (CO), and iron (Fe2+), which is used with 5-ALA. In the present study, we investigated the role of 5-ALA in the attenuation of acute renal IRI using a mouse model. Male Balb/c mice received 30 mg/kg 5-ALA with Fe2+ 48, 24, and 2 h before IRI and were subsequently subjected to bilateral renal pedicle occlusion for 45 min. The endogenous CO concentration of the kidneys from the mice administered 5-ALA/Fe2+ increased significantly, and the peak concentrations of serum creatinine and blood urea nitrogen decreased. 5-ALA/Fe2+ treatments significantly decreased the tubular damage and number of apoptotic cells. IRI-induced renal thiobarbituric acid-reactive substance levels were also significantly decreased in the 5-ALA/Fe2+ group. Furthermore, mRNA expression of HO-1, TNF-α, and interferon-γ was significantly increased after IRI. Levels of HO-1 were increased and levels of TNF-α and interferon-γ were decreased in the 5-ALA/Fe2+-pretreated renal parenchyma after IRI. F4/80 staining showed reduced macrophage infiltration, and TUNEL staining revealed that there were fewer interstitial apoptotic cells. These findings suggest that 5-ALA/Fe2+ can protect the kidneys against IRI by reducing macrophage infiltration and decreasing renal cell apoptosis via the generation of CO.
- Published
- 2013