Effects of nuclear factor E2 on inflammatory factors, oxidative stress indicators and apoptosis in folic acid-induced acute kidney injury model

Yudong Chu¹, Jiang Liu¹, Haojie Zhang¹, Huaqing Li^{2, *}

¹Department of Nephrology, Ningbo Medical Center Lihuili Hospital, Ningbo, PR China - ²Longyan First Hospital affiliated to Fujian Medical University, Longyan, PR China

Objective: This article explores the effects of nuclear factor E2-related factor 2 (Nrf2) on inflammatory factors, oxidative stress, and apoptosis indicators in folic acid-induced acute kidney injury models. 

Methods: Ten healthy clean-grade C57BL/6 (Nrf2^+/+) male mice and ten Nrf^2-/-male mice were collected, and all mice were divided into a Nrf2^+/+ (wild-type mice, retained the Nrf2 gene) + Folic acid + NaHCO₃ group, Nrf^2-/-(knock-out Nrf2 gene) + folic acid + NaHCO₃ group, Nrf2^+/+ + NaHCO³ group and a Nrf2^-/-+ NaHCO₃ group, with five animals each. A model of acute kidney injury in the group with Nrf2^+/+ + folic acid + NaHCO₃ and the group with Nrf2^-/- + folic acid + NaHCO₃ was established by intravenous injection of folic acid. The mRNA expression levels of oxidative stress-related indicators, inflammatory-related genes, and apoptosis-related indicators in each group of mice were compared. These indicators mainly include: quinone oxidoreductase 1 (NQO1), catalytic subunit of glutamylcysteine ligase (GCLC), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), caspase1, apoptosis-related speckle-like protein [PYCARD], and thioredoxin interacting protein 1/2 (TXNIP1/2)]. 

Results: The mRNA expression of NQO1, GCLC, and GCLMin in the Nrf2^+/+ and Nrf2^-/- group were significantly lower than NaHCO₃ group (P<0.05), and the mRNA expression of NQO1, GCLC, and GCLM in the Nrf2^-/- group was significantly lower than the Nrf2^+/+ group (P<0.05). The mRNA expression of IL-6 and TNF - α in the Nrf2^+/+ and Nrf2^-/- groups was significantly higher than the NaHCO₃ group (P<0.05). The mRNA expression level of IL-6 in the Nrf2^-/- group was significantly higher than the Nrf2^+/+ group (P<0.05). After NaHCO₃ + folate injection, TNF - α mRNA expression in the Nrf2^-/- group was significantly higher than the Nrf2^+/+ group (P<0.05). After the injection of folic acid + NaHCO3, the apoptosis degree of the Nrf2^+/+ group and Nrf2^-/- group was significantly lower than that of the NaHCO₃ group (P<0.05). Additionally, after the injection of folic acid + NaHCO3, the apoptosis degree of Nrf2^-/- group was significantly higher than the Nrf2^+/+ group (P<0.05). However, there was no significant difference in the expression of Caspase-1, pycard, or txnip1/2 mRNA in each group (P>0.05). 

Conclusion: Nrf2 may play a protective role in the acute renal injury induced by folic acid, which may be achieved by inhibiting inflammatory response, oxidative stress response, and apoptosis.