Hyperbaric oxygen therapy reduces renal lactate production

Abstract

Intrarenal hypoxia is an acknowledged factor contributing to the development of diabetic nephropathy. Hyperbaric oxygen (HBO) therapy is a well-known adjuvant treatment for several medical conditions, such as decompression sickness, infections, and wound healing. The underlying metabolic response of HBO is largely unknown. In this study, we investigated the effect of HBO on the intrarenal metabolic alteration in diabetes. Hyperpolarized [1-¹³C]pyruvate MRI was performed to assess intrarenal energy metabolism in normoglycemic controls and short-term (2 weeks) streptozotocin-induced diabetic rats with and without HBO for five consecutive days. HBO therapy blunted intrarenal lactate production, 3 days after the therapy, in both normoglycemic controls and diabetic rats without affecting either lactate dehydrogenase mRNA expression or activity. HBO therapy reduced lactate formation in both normoglycemic and hyperglycemic rats. These findings support hyperpolarized [1-¹³C]pyruvate MRI as a novel method for monitoring HBO therapy via the pyruvate to lactate conversion.

Keywords: MRI; Hyperpolarization; kidney; kidney metabolism; type 1 diabetes.

Figure 1

Outline of the experiment. The 5‐day hyperbaric oxygen therapy (HBO) treatment was initiated 11 days after induction of diabetes, and hyperpolarized [1‐¹³C]pyruvate MRI examination was performed 3 days after the end of HBO.

Figure 2

Renal lactate to pyruvate, alanine to pyruvate, and bicarbonate to pyruvate ratios in control and diabetic rats with and without HBO treatment. *P < 0.05 between control and diabetes. (Lactate) P < 0.0001* for group (between control and diabetes), P = 0.02 for treatment (HBO treatment groups), and P = 0.95 for interaction; (Alanine) P = 0.004* for group, P = 0.80 for treatment, and P = 0.19 for interaction; (Bicarbonate) P = 0.050 for group, P = 0.46 for treatment, and P = 0.36 for interaction.

Figure 3

Renal LDH enzyme activity and mRNA expression in controls and diabetes with and without HBO treatment. *P < 0.05 between control and diabetes. (LDH activity) P < 0.001 for group (between control and diabetes), P = 0.13 for treatment (HBO treatment groups), and P = 0.09 for interaction; (LDH expression) P = 0.62 for group, P = 0.15 for treatment, and P = 0.47 for interaction. LDH, lactate dehydrogenase.

Figure 4

Correlation between LDH and lactate to pyruvate ratio in controls and diabetes with (treated) and without HBO treatment (untreated). A statistically insignificant difference between the two slopes (P = 0.39) between the untreated groups, that is, the sum of untreated controls and diabetes animals (R ² = 0.53, P = 0.008), and the treated groups, that is, the sum of the HBO treated controls and the diabetes animals (R ² = 0.22, P = 0.11). The HBO‐treated animals showed a significantly reduced lactate to pyruvate ratio compared with untreated animals, P = 0.037. LDH, lactate dehydrogenase. *P < 0.05 between untreated and treated.

Figure 5

Blood‐oxygen‐level‐dependent magnetic resonance imaging in controls and diabetes with and without HBO treatment. *P < 0.05 between control and diabetes. (Cortex) P = 0.0005* for group (between control and diabetes), P = 0.35 for treatment (HBO treatment groups), and P = 0.25 for interaction; (Medulla) P = 0.02* for group, P = 0.98 for treatment, and P = 0.31 for interaction.