Isoliquiritigenin prevents Doxorubicin-induced hepatic damage in rats by upregulating and activating SIRT1

Fenugreek Seed Galactomannan Aqueous and Extract Protects against Diabetic Nephropathy and Liver Damage by Targeting NF-κB and Keap1/Nrf2 Axis

“…The levels of ROS/RNS in tissue lysate were measured using a DCF-based kit (#ab238535; Abcam, Cambridge, CB2 0AX, UK) and as previously used by others [ 42 , 43 , 44 ]. Homogenates levels of malondialdehyde (MDA) were measured using special rat assay kits (#10009055, Cayman, Ann Arbor, MI, USA) as validated previously in our labs and described previously by others [ 45 , 46 , 47 , 48 ]. The other rat-specific ELISA kits were used to measure the homogenate levels of superoxide dismutase (SOD) (#MBS036924, MyBioSource, San Diego, CA, USA); tumor necrosis factor-alpha (TNF-α) (#BMS622, ThermoFisher, Waltham, MA, USA), and interleukine-6 (IL-6) (#R6000B, R&D System, Minneapolis, MN, USA).…”

Concomitant Sub-Chronic Administration of Small-Size Gold Nanoparticles Aggravates Doxorubicin-Induced Liver Oxidative and Inflammatory Damage, Hyperlipidemia, and Hepatic Steatosis

“…However, the maximum increase in the serum levels of ALT, AST, and γ-GTT, as well as the severest hepatic damage, were observed in the group of rats that were administered the combined treatments of both AuNPs and DOX as compared to their individual effects. Based on these initial data, we become more confident that AuNPs exaggerate the hepatic damage of DOX, probably by its pro-oxidant and pro-inflammatory nature [ 8 ].…”

“…In the liver, the metabolism of DOX upregulates numerous ROS-generating enzymes that promote oxidative and inflammatory damage [ 7 ]. Short and long-term treatment with DOX was associated with higher levels of hepatic ROS, TNFα, and IL-6, over-activation of NF-κB, and reduced activities and expression of Nrf2 [ 3 , 4 , 6 , 8 , 30 , 31 , 32 ]. In addition, short-term treatment with AuNPs promotes hepatic and renal oxidative stress and inflammation by generating ROS and inflammatory cytokines, scavenging GSH, consuming SOD and CAT, and activating NF-κB [ 15 , 16 , 18 , 19 , 21 ].…”

“…Yet, these data cannot precisely identify whether Nrf2 locates upstream or downstream of NF-κB during this toxicity. However, we have recently shown that DOX could promote liver damage by modulating these pathways through suppressing SIRT1, which normally activates Nrf2/antioxidant axis and suppresses NF-κB p65 and inflammation [ 8 ]. Hence, targeting SIRT1 could represent a novel target to reveal the hepatic toxicity induced by AuNPs.…”

“…Doxorubicin (DOX) is one of the most known anthracycline chemotherapeutic antibiotic drugs that is associated with hepatic damage and steatosis due to its ability to damage DNA and generate high levels of reactive oxygen species (ROS), which subsequently trigger oxidative stress, inflammation, fibrosis, and apoptosis [ 3 , 4 ]. Mechanisms by which DOX promotes hepatic oxidative stress and damage have been recently reviewed in excellent journals and included both enzymatic and non-enzymatic pathways (i.e., activation of NADPH reductase, formation of DOX/Ferrous (Fe 2+ ) complex, suppression of the antioxidant transcription factor, the nuclear factor-erythroid factor 2-related factor 2 (Nrf2), depletion of cellular antioxidants (i.e., glutathione (GSH) and other enzymes), and lipid peroxidation [ 5 , 6 , 7 , 8 ]. However, the hepatic inflammatory and apoptotic responses associated with DOX are characterized by upregulation/activation of the nuclear factor kappa-beta (NF-κB), higher levels of inflammatory cytokines (i.e., tumor necrosis-α (TNF-α), and interleukine-6 (IL-6), upregulation of Bax/p53, and release of cytochrome-c from the mitochondria [ 3 , 4 , 8 , 9 ].…”