Figure 1.
Chemotherapy Administration Increases Circulating Corticosterone and Induces Systemic Inflammation.
Wild type mice (8–10/group) were treated with CAF chemotherapy and sacrificed 4 hours later. (A) Plasma corticosterone concentration. (B) Hypothalamic and (C) splenic inflammatory cytokine gene expression was measured by qPCR. * = P<0.05, and *** = P<0.001 vs. sham-treated mice as measured by Student’s t-test. V = Vehicle, C = Chemotherapy.
Figure 2.
Chemotherapy Administration Produces Muscle Mass Loss in a Glucocorticoid-dependent Manner.
GRLox/Lox and mGRKO mice (n = 6–13/group) were treated with CAF chemotherapy and sacrificed 18 hours later. (A) Food intake and (B) body weight were measured. (C, D) Gastrocnemius muscle was weighed, normalized to pre-treatment body weight and presented as weight loss relative to sham-treated control mice of the same genotype. * = P<0.05, ** = P<0.01, and *** = P<0.001 vs. sham-treated mice of the same genotype as measured by two-way ANOVA with Bonferroni post-test. V = Vehicle, C = Chemotherapy.
Figure 3.
The Induction of Catabolic Gene Expression in Skeletal Muscle Requires Glucocorticoids.
GRLox/Lox and mGRKO mice (n = 6–13/group) were treated with CAF chemotherapy and sacrificed 18 hours later. (A, B, C, D) Gastrocnemius muscle gene expression was measured by quantitative real time PCR with GAPDH as an endogenous control. * = P<0.05, ** = P<0.01, and *** = P<0.001 vs. sham-treated mice of the same genotype as measured by two-way ANOVA with Bonferroni post-test. V = Vehicle, C = Chemotherapy.
Figure 4.
Chemotherapy Produces the Specific Atrophy of Type IIb Muscle Fibers That is Dependent on Glucocorticoids.
GRLox/Lox and mGRKO mice (n = 6–13/group) were treated with CAF chemotherapy and sacrificed 18 hours later. (A) Cryosections of tibialis anterior muscle were immunostained with antibodies to distinct myosin isoforms and the fiber cross sectional area of IIb (green), IIa (blue) and IId/x (black) fibers was measured. (B) Representative images of tibialis anterior muscles that were cut in cross section and immunostained with antibodies against laminin (white), myosin IIb (green) myosin IIa (blue). Scale bar = 100 µM.
Figure 5.
The Gene Expression Signature of Chemotherapy-Induced Cardiotoxicity Contains Glucocorticoid Dependent and Independent Elements.
GRLox/Lox and mGRKO mice (n = 6–13/group) were treated with CAF chemotherapy and sacrificed 18 hours later. (A, B, C, D) Heart gene expression was measured by quantitative real time PCR with GAPDH as an endogenous control. * = P<0.05, ** = P<0.01, and *** = P<0.001 vs. sham-treated mice of the same genotype as measured by two-way ANOVA with Bonferroni post-test. V = Vehicle, C = Chemotherapy.