Bromoacetic acid causes oxidative stress and uric acid metabolism dysfunction via disturbing mitochondrial function and Nrf2 pathway in chicken kidney

Abstract

Since the outbreak of COVID‐19, widespread utilization of disinfectants has led to a tremendous increase in the generation of disinfection byproducts worldwide. Bromoacetic acid (BAA), one of the common disinfection byproducts in the environment, has triggered public concern because of its adverse effects on urinary system in mammals. Nevertheless, the BAA‐induced nephrotoxicity and potential mechanism in birds still remains obscure. According to the detected content in the Taihu Lake Basin, the model of BAA exposure in chicken was established at doses of 0, 3, 300, 3000 μg/L for 4 weeks. Our results indicated that BAA exposure caused kidney swelling and structural disarrangement. BAA led to disorder in renal function (CRE, BUN, UA) and increased apoptosis (Bax, Bcl‐2, caspase3). BAA suppressed the expression of mitochondrial biogenesis genes (PGC‐1α, Nrf1, TFAM) and OXPHOS complex I genes (ND1, ND2, ND3, ND4, ND4L, ND5, ND6). Subsequently, BAA destroyed the expression of Nrf2 antioxidant reaction genes (Nrf2, Keap1, HO‐1, NQO1, GCLM, GCLC). Furthermore, renal oxidative damage led to disorder in uric acid metabolism genes (Mrp2, Mrp4, Bcrp, OAT1, OAT2, OAT3) and exacerbated destruction in renal function. Overall, our study provided insights into the potential mechanism of BAA‐induced nephrotoxicity, which were important for the clinical monitoring and prevention of BAA.

Mitochondrial dysfunction following repeated administration of alprazolam causes attenuation of hippocampus-dependent memory consolidation in mice

“…Proteomic results showed that a large number of DEPs were enriched in mitochondrial metabolism pathways, suggesting abnormal mitochondrial energy metabolism. First, significant changes complexes I (Ndufc2 [ 50 , 51 ], Ndufs5, ND4 [ 29 , 52 ]), complexes IV (COX 4 [ 53 , 54 ], COX 6), and ATP 8 [ 55 ] indicated mETC disorders. Second, differential expression of mitochondrial fission protein FIS1 [ 56 ] and fusion protein OPA1 [ 57 , 58 ] suggested that mitochondrial homeostasis is disrupted.…”

“…In addition, many DEPs were enriched in the neurodegenerative diseases' pathway, including Alzheimer's, Parkinson's, and Huntington's diseases. AGING The protein network analysis of significantly differentiated proteins (Figure 2A) revealed that these are mitochondrial complex I-related proteins [28][29][30], mitochondrial complex II-related proteins [31], mitochondrial complex IV-related proteins [32,33], and mitochondrial dynamics-related proteins [34], which interfere with energy metabolism processes primarily by influencing the mitochondrial electron transport chain (mETC) [35]. Most importantly, the 6 DEPS in above proteomic analysis were selected for further Western blotting validation, and the data (Figure 2B) showed that COX6A1 (p < 0.05), Ndufab1 (p < 0.05) and OPA1 (p < 0.01) in the Alp group were significantly up-regulated compared to the control group, conversely, Ndufs6 (p < 0.05), FIS1 (p < 0.05) and ND4 (p < 0.01) were significantly down-regulated.…”

Nrf2: A Main Responsive Element of the Toxicity Effect Caused by Trichothecene (T-2) Mycotoxin

“…NRF1 then activated TFAM and ultimately promoted mitochondrial biogenesis [66]. NRF1 and TFAM are the downstream targets of PGC-1α [67]. A Nrf2 knockdown cell model was created to show how Nrf2 contributes to mitochondrial biogenesis following exposure to T-2 toxin.…”