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The Na/K-ATPase amplifies oxidant signaling, and its attenuation with pNaKtide antagonizes adipogenesis.

We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic cardiomyopathy reversed many of the phenotypical features. Attenuation of Na/K-ATPase oxidant amplification may be a potential strategy for clinical therapy of this disorder.

The authors report significant worsening of a pre-existing neuropathy in six patients who received "non-toxic" dosages of known neurotoxic agents. Before treatment, baseline total neuropathy score (TNS) averaged 9.5 (range 0 to 19). After chemotherapy (Taxol [125 to 175 mg/m(2) x 4]; vincristine [2 to 5 mg]; cisplatin [40 mg/m(2) x 8]; and thalidomide [60 g]), the TNS averaged 22 (range 13 to 29). The authors conclude that functionally disabling toxic neuropathy can occur in patients with pre-existing neuropathy at standard doses.