Treatment with inhibitors of the NF-kappaB pathway improves whole body tension development in the mdx mouse.
The whole body tension (WBT) method was used to evaluate the hypothesis that long term treatment with NF-kappaB inhibitors improves the total forward pulling tension exerted by the limb musculature of the mdx mouse. Mdx mice exhibited significantly reduced WBT values and more profound weakening during the course of generating multiple forward pulling movements than age-matched nondystrophic mice. Long term treatment with the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) did not significantly reduce nuclear p65 activation in the costal diaphragm, but increased WBT by 12% in mature (12 month) mice. Daily treatment (30 days) of 1 month old mdx mice with the inhibitor ursodeoxycholic acid (UDCA) reduced costal diaphragm nuclear p65 activation by 40% and increased WBT by 21%. These results indicate that treatment with NF-kappaB inhibitors improves WBT in the mdx mouse and further establishes the utility of the WBT procedure in assessing therapeutic efficacy.
Siegel
Ashley L
AL
Dept. of Physiology, Kirksville College of Osteopathic Medicine, AT Still University, Kirksville, MO 63501, USA.
Bledsoe
Cathy
C
Lavin
Jesse
J
Gatti
Francesca
F
Berge
Jonas
J
Millman
Gregory
G
Turin
Eric
E
Winders
W Tyler
WT
Rutter
John
J
Palmeiri
Beniamino
B
Carlson
C George
CG
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D052580:Muscle Stretching Exercises / Q000009:adverse effects; D009129:Muscle Tonus / Q000187:drug effects* / Q000502:physiology; D018908:Muscle Weakness / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013859:Thiocarbamates / Q000494:pharmacology* / Q000627:therapeutic use; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use
D000975:Antioxidants; D002756:Cholagogues and Choleretics; D016328:NF-kappa B; D011759:Pyrrolidines; C498144:Rela protein, mouse; D013859:Thiocarbamates; D051996:Transcription Factor RelA; C020972:pyrrolidine dithiocarbamic acid; D014580:Ursodeoxycholic Acid