Benzanthrone

Balb/c (female, 6-8 weeks old, 18-20 g)^[1]

3.25 mg/kg; 7.5 mg/kg; 15 mg/kg

i.p.; daily; 1 week

Caused dose-dependent inflammation at 7.5 mg/kg and 15 mg/kg.
Induced splenic hyperplasia with megakaryocyte infiltration, and lung alveolar septal thickening, edema, and focal hemorrhages at 15 mg/kg.
Showed no notable changes at 3.25 mg/kg.
Increased splenic MPO activity by 157% and lung MPO activity by 193% at 7.5 mg/kg.
Increased splenic MPO activity by 571% and lung MPO activity by 666% at 15 mg/kg.
Increased ROS generation (2-fold), lipid peroxidation (106%), and protein carbonyl content (25%); decreased GSH content (55%), SOD activity (24%), GST activity (37%), GR activity (34%), catalase activity (12%), and GPx activity (74%); reduced Nrf2 protein levels; and increased γ-H2AX protein levels (1.9-fold) in spleen at 7.5 mg/kg.
Increased ROS generation (2.9-fold), lipid peroxidation (450%), and protein carbonyl content (173%); decreased GSH content (73%), SOD activity (66%), GST activity (75%), GR activity (55%), catalase activity (29%), and GPx activity (85%); further reduced Nrf2 protein levels; and increased γ-H2AX protein levels (2.2-fold) in spleen at 15 mg/kg.
Increased TNF-α (1.2-fold), IL-4 (1.5-fold), and IL-1 (81-fold) in serum at 7.5 mg/kg.
Increased IL-17 (4.8-fold), TNF-α (1.52-fold), IFN-γ (4.2-fold), IL-4 (4.25-fold), IL-10 (12.3-fold), and IL-1 (427-fold) in serum at 15 mg/kg.
Dose-dependently increased mRNA levels of IL-4, IL-1, IL-10, IFN-γ, and TNF-α in splenic cytokine at 7.5 mg/kg and 15 mg/kg.
Increased p-JNK (2.5-fold), p-ERK (1.6-fold), and p-p38 (2-fold) at 7.5 mg/kg.
Increased p-JNK (2.9-fold), p-ERK (2.2-fold), and p-p38 (2.3-fold) at 15 mg/kg.
Increased p-NF-κB (1.8-fold), c-fos (1.9-fold), c-jun (2-fold), COX-2 (2.2-fold), and iNOS (2-fold) at 7.5 mg/kg.
Increased p-NF-κB (2.3-fold), c-fos (2.9-fold), c-jun (3-fold), COX-2 (2.9-fold), and iNOS (3-fold) at 15 mg/kg.

Balb/c (female)^[1]

0.3% (sensitization); 0.15% (challenge)

topical; once daily for 3 consecutive days (sensitization); single dose (challenge)

Increased ear swelling by 69% compared to vehicle control.
Significantly elevated ear pinna MPO activity.
Induced epidermal hyperplasia protruding into the dermis and infiltration of mixed inflammatory cells.