Troxerutin attenuates diet‐induced oxidative stress, impairment of mitochondrial biogenesis and respiratory chain complexes in mice heart

Abstract

Summary Mitochondrial abnormality is thought to play a key role in cardiac disease originating from the metabolic syndrome (MS). We evaluated the effect of troxerutin (TX), a semi‐synthetic derivative of the natural bioflavanoid rutin, on the respiratory chain complex activity, oxidative stress, mitochondrial biogenesis and dynamics in heart of high fat, high fructose diet (HFFD) ‐induced mouse model of MS. Adult male Mus musculus mice of body weight 25‐30 g were fed either control diet or HFFD for 60 days. Mice from each dietary regimen were divided into two groups on the 16th day and were treated or untreated with TX (150 mg/kg body weight [bw], per oral) for the next 45 days. At the end of experimental period, respiratory chain complex activity, uncoupling proteins (UCP)‐2 and ‐3, mtDNA content, mitochondrial biogenesis and dynamics, oxidative stress markers and reactive oxygen species (ROS) generation were analyzed. Reduced mtDNA abundance with alterations in the expression of genes related to mitochondrial biogenesis and fission and fusion processes were observed in HFFD‐fed mice. Disorganized and smaller mitochondria, reduction in complexes I, III and IV activities (by about 55%) and protein levels of UCP‐2 (52%) and UCP‐3 (46%) were noted in these mice. TX administration suppressed oxidative stress, improved the oxidative capacity and biogenesis and restored fission/fusion imbalance in the cardiac mitochondria of HFFD‐fed mice. TX protects the myocardium by modulating the putative molecules of mitochondrial biogenesis and dynamics and by its anti‐oxidant function in a mouse model of MS.

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].…”

“…The body weight of mice was assessed daily prior to administration of the administered treatment to confirm the experimental model of 5-FU induced intestinal mucositis. The TRX doses considered in the current study are in accordance with those in previous published studies [19][20][21][22]61]. daily prior to administration of the administered treatment to confirm the experimental model of 5-FU induced intestinal mucositis.…”

“…daily prior to administration of the administered treatment to confirm the experimental model of 5-FU induced intestinal mucositis. The TRX doses considered in the current study are in accordance with those in previous published studies [19][20][21][22]61]. To investigate the role of cyclooxygenase 2 (COX-2) enzyme during TRX treatment of 5-FUinduced intestinal mucositis, COX-2 was blocked by an intraperitoneal (i.p) injection of 7.5 mg/kg of CLX.…”

“…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].…”

Transcriptomic analysis of gene expression in mice treated with troxerutin

“…In addition to the above, Hbq1a encodes hemoglobin, theta 1A, which is closely connected with oxygen and iron binding, and impact the activity of oxygen transporter. It may be associated with anti-oxidative effects of TX[ 83 ]. GM5526 is mainly responsible for skeletal muscle tissue development and muscle filament sliding.…”