Protective Effect of Boswellic Acids against Doxorubicin‐Induced Hepatotoxicity: Impact on Nrf2/HO‐1 Defense Pathway

Abstract

The current study aimed to investigate the potential protective role of boswellic acids (BAs) against doxorubicin- (DOX-) induced hepatotoxicity. Also, the possible mechanisms underlying this protection; antioxidant, as well as the modulatory effect on the Nrf2 transcription factor/hem oxygenase-1 (Nrf2/HO-1) pathway in liver tissues, was investigated. Animals were allocated to five groups: group 1: the saline control, group 2: the DOX group, animals received DOX (6 mg/kg, i.p.) weekly for a period of three weeks, and groups 3–5: animals received DOX (6 mg/kg, i.p.) weekly and received protective doses of BAs (125, 250, and 500 mg/kg/day). Treatment with BAs significantly improved the altered liver enzyme activities and oxidative stress markers. This was coupled with significant improvement in liver histopathological features. BAs increased the Nrf2 and HO-1 expression, which provided protection against DOX-induced oxidative insult. The present results demonstrated that BAs appear to scavenge ROS and inhibit lipid peroxidation and DNA damage of DOX-induced hepatotoxicity. The antioxidant efficacy of BAs might arise from its modulation of the Nrf2/HO-1 pathway and thereby protected liver from DOX-induced oxidative injury.

Metformin Protects From Rotenone–Induced Nigrostriatal Neuronal Death in Adult Mice by Activating AMPK-FOXO3 Signaling and Mitigation of Angiogenesis

“…Nrf2 nuclear localization in PD was observed, and the abundant oxidative stress outweighs Nrf2 capacity to prevent neuronal degeneration (Ramsey et al, 2007). Nrf2 enhances the expression of cellular antioxidant defenses, such as glutamate cysteine ligase, which catalyzes de novo synthesis of GSH (Kugiyama et al, 1998;Kansanen et al, 2013), HO-1 (Barakat et al, 2018), and thioredoxin (Ashino et al, 2013). Therefore, downregulation of Nrf2 expression was accompanied by lower HO-1 and thioredoxin expression according to the current study findings.…”

Yiqi Fumai lyophilized injection attenuates doxorubicin-induced cardiotoxicity, hepatotoxicity and nephrotoxicity in rats by inhibition of oxidative stress, inflammation and apoptosis

“…The results were showed as the mean AE SEM (n ¼ 10) *p < 0.05, **p < 0.01, ***p < 0.001 vs. DOX group; # p < 0.05, ## p < 0.01, ### p < 0.001 vs. control group. 8,[40894][40895][40896][40897][40898][40899][40900][40901][40902][40903][40904][40905][40906][40907][40908][40909][40910][40911] This journal is © The Royal Society of Chemistry 2018…”

“…5,6 Although the mechanisms responsible for DOX-induced toxicity are still not quite clear, most researchers nd that nicotinamide adenine dinucleotide phosphate-(NADPH-) dependent cellular reductase can transform DOX into semiquinone free radicals which can increase reactive oxygen species (ROS) to damage lipids and proteins, eventually leading to organ injuries. 7,8 Unfortunately, DOX leads to severe clinical toxicities in kidney too. 9 There are many studies indicating that DOX-induced nephrotoxicity is caused by ROS which induces lipid peroxidation, damages renal cells, and increases glomerular capillary permeability and tubular atrophy.…”

Sexual Dimorphism in Doxorubicin-induced Systemic Inflammation: Implications for Hepatic Cytochrome P450 Regulation

“…DOX is known for its cardiotoxic effects that may lead to cardiac dysfunction and heart failure [1]. In addition to cardiotoxicity, DOX has also been shown to cause hepatotoxicity [2][3][4][5][6], gastro-intestinal toxicity [7], and nephrotoxicity [8,9]. Although DOX-induced toxicity is likely to be multi-factorial, inflammation has been shown to be a central player in mediating DOX-induced toxicity [10][11][12][13][14].…”