Effects of Dimethyl Sulfoxide, Pyrrolidine Dithiocarbamate, and Methylprednisolone on Nuclear Factor-κB and Heat Shock Protein 70 in a Rat Model of Hemorrhagic Shock

Abstract

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). 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. 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). 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.