Loss of muscle mass related to anti-cancer therapy is a major concern in cancer patients, being associated with important clinical endpoints including survival, treatment toxicity and patient-related ...outcomes. We investigated effects of voluntary exercise during cisplatin treatment on body weight, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, P < 0.001), lean body mass (20.6%, P = 0.001), as well as anorexia, impaired muscle strength (22.5% decrease, P < 0.001) and decreased glucose tolerance. In addition, cisplatin impaired Akt-signalling, induced genes related to protein degradation and inflammation, and reduced muscle glycogen content. Voluntary wheel running during treatment attenuated body weight loss by 50% (P < 0.001), maintained lean body mass (P < 0.001) and muscle strength (P < 0.001), reversed anorexia and impairments in Akt and protein degradation signalling. Cisplatin-induced muscular inflammation was not prevented by voluntary wheel running, nor was glucose tolerance improved. Exercise training may preserve muscle mass in cancer patients receiving cisplatin treatment, potentially improving physical capacity, quality of life and overall survival.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Conflicting observations have been reported concerning the role of
CD
1d‐dependent natural killer T (
NKT
) cells in contact hypersensitivity (
CHS
), supporting either a disease‐promoting ...or downregulatory function. We studied the role of
NKT
cells in
CHS
by comparing the immune response in
CD
1d knockout (
CD
1d
KO
) and wild‐type (Wt) mice after contact allergen exposure. For induction of
CHS
, C57
BL
/6
CD
1d
KO
mice (
n
= 6) and C57
BL
/6 Wt mice (
n
= 6) were sensitised with 1% (w/v) dinitrochlorobenzene (
DNCB
) or vehicle for three consecutive days and subsequently challenged with a single dose of 0.5%
DNCB
(w/v) on the ears fifteen days later. We demonstrate that
CD
1d
KO
mice, as compared with Wt littermates, have more pronounced infiltration of mononuclear cells in the skin (29.1% increase;
P
< 0.001), lower frequencies of interleukin‐10
+
B cells (B
regs
) in the spleen (53.2% decrease;
P
< 0.05) and peritoneal cavity (80.8% decrease;
P
< 0.05) and increased production of interferon‐
γ
(3‐fold;
P
< 0.05) after
DNCB
sensitisation and challenge, which suggests an important regulatory and protective role of
CD
1d‐dependent
NKT
cells in
CHS
in our model, at least in part via regulation of
IL
‐10 producing B
regs
.
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