Effects of dimethyl sulfoxide, pyrrolidine dithiocarbamate, and methylprednisolone on nuclear factor-kappaB and heat shock protein 70 in a rat model of hemorrhagic shock.
BACKGROUND
Nuclear factor kappa B (NF-kappaB) is a transcription factor involved in the inflammatory response. Heat shock protein 70 (HSP70) is involved in the cell protection from various stresses. The aim of this study was to evaluate the effects of dimethyl sulfoxide (DMSO), pyrrolidine dithiocarbamate (PDTC), and methylprednisolone (MP) on liver, renal, and intestinal activation of NF-kappaB and HSP70 in a rat model of hemorrhagic shock (HS).


METHODS
Sixty rats were randomized in 6 groups: sham-operated; only HS; HS and resuscitation with blood plus normal saline (NS); HS and resuscitation with blood/NS and 6 mg/kg DMSO; HS and resuscitation with blood/NS and 100 mg/kg PDTC; HS and resuscitation with blood/NS and 30 mg/kg MP. Rats were subjected to HS by blood removal to a mean arterial pressure of 35 to 40 mm Hg through the femoral artery. After 1-hour shock-period, the animals were resuscitated according to the experimental protocol. NF-kappaB and HSP70 expression in liver, kidney, and small intestine was analyzed 1 and 3 hours after resuscitation by immunohistochemistry.


RESULTS
HS upregulated NF-kappaB activation and HSP70 expression (p < 0.05). Resuscitation was not associated with a further increase in NF-kappaB and HSP70 activation. DMSO, PDTC, and MP administration resulted in a decreased liver, renal, and intestinal activation of NF-kappaB associated with an increase of HSP70 expression (p < 0.05).


CONCLUSIONS
Our results suggest that treatment with DMSO, PDTC, and MP can modulate the expression of NF-kappaB and HSP70 after HS in rats. This modulation may have potential effects in HS through inhibition of the NF-kappaB-dependent production of proinflammatory mediators.
Bini
Roberto
R
From the Chirurgia d'Urgenza, Dipartimento di Discipline Medico-Chirurgiche, Università di Torino, Torino, Italy.
Olivero
Giorgio
G
Trombetta
Antonella
A
Castagna
Elisabetta
E
Cotogni
Paolo
P
D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000503:physiopathology; D013859:Thiocarbamates / Q000494:pharmacology*; D015854:Up-Regulation
D018840:HSP70 Heat-Shock Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D008775:Methylprednisolone; D004121:Dimethyl Sulfoxide