5-Aminolevulinic acid combined with ferrous iron induces carbon monoxide generation in mouse kidneys and protects from renal ischemia-reperfusion injury.

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 (Fe(2+)), 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 Fe(2+) 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/Fe(2+) increased significantly, and the peak concentrations of serum creatinine and blood urea nitrogen decreased. 5-ALA/Fe(2+) 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/Fe(2+) 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/Fe(2+)-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/Fe(2+) can protect the kidneys against IRI by reducing macrophage infiltration and decreasing renal cell apoptosis via the generation of CO.

Antitumor effect of combination of hyperthermotherapy and 5-aminolevulinic acid (ALA).

BACKGROUND: 5-Aminolevulinic acid (ALA) is a precursor of heme. ALA is used as a photosensitive substance in photodynamic diagnosis (PDD) and photodynamic therapy (PDT) because heme metabolism is abnormal in tumor cells and a photosensitive metabolite of heme synthesis from ALA, protoporphyrin IX (PpIX), specifically accumulates in tumors. We investigated the enhancement of the antitumor effect by combination of ALA and hyperthermotherapy (HT) using a transplanted tumor model with Lewis lung carcinoma cells (3LL) in mice. MATERIALS AND METHODS: Animals were divided into four test groups: control (untreated), HT, and HT plus ALA (100 or 300 mg/kg) groups, and HT by bathing at 43°C for 20 min was performed at five days after transplantation. ALA was administered once at the above doses three hours before HT by intraperitoneal injection. RESULTS: The tumor sizes at five days after HT were 5.2- and 2.6-times greater than those at the time of HT in the control and HT groups, respectively. In contrast, PpIX accumulation in the tumor region was noted three hours after ALA administration, the HT+ALA group given at 100 or 300 mg/kg of ALA inhibited tumor growth to 1.3- and 1.1-times increases in the tumor size. CONCLUSION: Therefore, ALA administration markedly enhanced the tumor growth-inhibitory effect of HT.