Acute Exposure of Apigenin Induces Hepatotoxicity in Swiss Mice

Abstract

Apigenin, a dietary flavonoid, is reported to have several therapeutic effects in different diseases including cancer. Toxicity of Apigenin is however, least explored, and reports are scanty in literature. This warrants dose-specific evaluation of toxicity in vivo. In the present study, Apigenin was administered intraperitoneally to Swiss mice at doses of 25, 50, 100 and 200 mg/kg. Serum levels of alanine amino transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase (ALP) were measured along with the examination of liver histology, reactive oxygen species (ROS) in blood, lipid peroxidation (LPO), glutathione level, superoxide dismutase activity, catalase activity, glutathione S-transferase activity and gene expression in liver tissue. Increase in ALT, AST, ALP, ROS, ratio of oxidized to reduced glutathione (GSSG/GSH) and LPO, altered enzyme activities along with damaged histoarchitecture in the liver of 100 or 200 mg/kg Apigenin treated animals were found. Microarray analysis revealed the differential expression of genes that correspond to different biologically relevant pathways including oxidative stress and apoptosis. In conclusion, these results suggested the oxidative stress induced liver damage which may be due to the regulation of multiple genes by Apigenin at higher doses in Swiss mice.

Attenuation of oxidative damage and inflammatory responses by apigenin given to mice after irradiation

“…This is consistent with the results described in a recent publication in which it was found that hepatotoxicity occurred in Swiss mice only when they were treated with concentrations of apigenin of 100 mg/kg bw and greater [37]. It also has been determined that 150 mg/kg bw was the LD 50 value for apigenin given to mice by IP injection [38].…”

Chitosan coated curcumin nanocrystals augment pharmacotherapy via improved pharmacokinetics and interplay of NFκB, Keap1 and Nrf2 expression in Gram negative sepsis

“…CUR has been reported to reduce TNF-α secretion via down regulation NFκB and PPAR-γ pathway 27 whereas chitosan can directly bind with LPS to reduce interaction with TLR-4 receptors in accordance with previously published reports 21, 28 . 45 Chi-CUR-NC4b also resulted in reduction of oxidative stress as well as neutrophil migration as indicated by levels of myeloperoxidase in tissues, specifically lung and liver. Tissue injury is a most important hallmark in pathophysiology of sepsis usually worsening to organ failure and death.…”

“…The samples were analyzed for changes in size and zeta potential 45 after premilling and then 5, 10, 15, and 20 homogenization cycles respectively. The formulation was optimized by varying type (Tween 80 or PF 68) and concentrations (at 1 and 2% w/v) of stabilizers; Number of homogenization cycles (premilling, 5, 10, 15 and 20 cycles respectively) and outcomes were evaluated in 50 terms of NC size, PDI, and zeta potential.…”

“…Specifically, in 45 case of gut derived sepsis prompt induction to antibiotic therapy is not capable to prevent multiple organ failure and death by overwhelming inflammatory response indicating an unmet and urgent need for developing novel therapies for sepsis 1 . CUR is a phenolic derivative and is reported to have a number of 50 properties like anticancer, anti-inflammatory 2 , antioxidant activities 3 .…”

Luteolin as a potent anti-leishmanial agent against intracellular Leishmania tropica parasite

“…All the mice were cured at or after 120 th day of infection, when compounds 1 -5 were given; . Apigenin showed cytotoxic activity at 8.30 µg/ml and induced hepatotoxicity at 100 and 200 mg/kg whereas it was non-toxic in 25 and 50 mg/kg [25]. In another study, apigenin decreased viability of human hepatoma HepG2 cells up to 42 % [24].…”