Troxerutin Reduces Kidney Damage against BDE‐47‐Induced Apoptosis via Inhibiting NOX2 Activity and Increasing Nrf2 Activity

Abstract

2,2,4,4-Tetrabromodiphenyl ether (BDE-47), one of the persistent organic pollutants, seriously influences the quality of life; however, its pathological mechanism remains unclear. Troxerutin is a flavonoid with pharmacological activity of antioxidation and anti-inflammation. In the present study, we investigated troxerutin against BDE-47-induced kidney cell apoptosis and explored the underlying mechanism. The results show that troxerutin reduced renal cell apoptosis and urinary protein secretion in BDE-47-treated mice. Western blot analysis shows that troxerutin supplement enhanced the ratio of Bcl-2/Bax; inhibited the release of cytochrome c from mitochondria, the activation of procaspase-9 and procaspase-3, and the cleavage of PARP; and reduced FAS, FASL, and caspase-8 levels induced by BDE-47. In addition, troxerutin decreased the production of reactive oxygen species (ROS) and increased the activities of antioxidative enzymes. Furthermore, troxerutin blunted Nrf2 ubiquitylation, enhanced the activity of Nrf2, decreased the activity of NOX2, and ameliorated kidney oxidant status of BDE-47-treated mice. Together, these results confirm that troxerutin could alleviate the cytotoxicity of BDE-47 through antioxidation and antiapoptosis, which suggests that its protective mechanism is involved in the inhibition of apoptosis via suppressing NOX2 activity and increasing Nrf2 signaling pathway.

Troxerutin Prevents 5-Fluorouracil Induced Morphological Changes in the Intestinal Mucosa: Role of Cyclooxygenase-2 Pathway

“…As shown by our study, TRX treatment (100 mg/kg) reverses the 5-FU-induced increase of MDA levels and prevents GSH consumption in mice. The antioxidant effect of TRX shown in the present study has also been reported by several published studies in different experimental models [17][18][19]21,[57][58][59][60][61].…”

“…Troxerutin (TRX) is a semi-synthetic flavonoid, derived from rutin, which is extracted from Dimorphandra gardneriana. This compound has various pharmacological activities, including antioxidant [17][18][19], anti-inflammatory [20], anti-apoptotic [21,22], and antiedematogenic [23,24]. Further, it is a potent therapeutic agent for neuropathic pain [25].…”

Oxidative Stress, Induced by Sub-Lethal Doses of BDE 209, Promotes Energy Management and Cell Cycle Modulation in the Marine Fish Cell Line SAF-1

“…In our experiment, the levels of NRF-2 increased, suggesting that PBDEs exposure was able to activate the NRF-2 response in SAF-1 cells, probably via oxidative stress. Our observations agree with other works that reported the upregulation of NRF-2 via oxidative stress after PBDEs exposure, both in vivo [85] and in vitro [57,86].…”

Dexmedetomidine Ameliorates Acute Stress‐Induced Kidney Injury by Attenuating Oxidative Stress and Apoptosis through Inhibition of the ROS/JNK Signaling Pathway

“…A recent study showed that oxidative stress induces mitochondrial apoptosis, which in turn leads to kidney injury [ 61 ]. To determine whether acute stress induced kidney injury by activating the mitochondrial apoptosis pathway, follow-up studies were performed.…”