Background: Methylmalonic aciduria is an inborn error of metabolism that causes renal failure and tubulointerstitial (TI) nephritis as complications. This study aimed to examine the levels of expression of several genes related to inflammation, oxidative stress, and mitochondrial function in the renal cortex of rats receiving methylmalonic acid (MMA).
Methods: Rats received MMA subcutaneously for a month. Tumor necrosis factor alpha (TNFα), nuclear factor-kappa B, interleukin 1 beta (IL-1β), and cyclooxygenase 2 (COX-2) genes were examined by real-time polymerase chain reaction. We also examined transforming growth factor beta (TGF-β) related to TI fibrosis, c-FOS, belonging to the immediate early gene family of transcription factors, and expression of SIRT1, related to energy production.
Results: There was significantly higher expression of TNFα and a trend toward a higher level of TGF-β transcripts in the methylmalonic model group compared with the controls. However, SIRT1 expression was not different among the groups. Urinary MMA excretion correlated positively with mRNA level of TGF-β. The expression of COX-2 was positively associated with the expression of c-FOS and inversely related to the expression of IL-1β.
Conclusions: The higher levels of TNFα and TGF-β transcripts suggest inflammation and differentiation processes in the renal cortex in rats because of MMA. After 1 month of MMA injections, expression levels of SIRT1 were not affected, suggesting mitochondrial preservation in early stages of the disease.