Yuka Kohda* and Munekazu Gemba
Division of Pharmacology, Osaka University of Pharmaceutical Sciences,
Nasahara, Takatsuki, Osaka 569-1094, Japan
*Corresponding author. FAX: +81-726-90-1053
E-mail: kohda@oysun01.oups.ac.jp
Abstract: Intracellular signaling pathways of cAMP and protein kinase
C (PKC) have been suggested to modulate the generation of free radicals.
We investigated the effects of cAMP and phorbol myristate acetate (PMA),
a PKC activator, on cephaloridine (CER)-induced renal cell injury, which
has been reported to be due to the generation of free radicals. Incubation
of rat renal cortical slices with CER resulted in increases in lipid peroxidation
and lactate dehydrogenase (LDH) release and in decreases in gluconeogenesis
and p-aminohippurate (PAH) accumulation in rat renal cortical slices,
suggesting free radical-induced injury in slices exposed to CER. A derivative
of cAMP ameliorated not only the increase in lipid peroxidation but also
the renal cell damage induced by CER. This amelioration by a cAMP derivative
of lipid peroxidation and renal cell damage caused by CER was blocked by
KT 5720, a protein kinase A (PKA) inhibitor. Lipid peroxidation and the
indices of cell injury were increased by PMA. PMA also enhanced CER-induced
lipid peroxidation and cell damage in the slices. This enhancement by PMA
of CER-induced injury was blocked by H-7, a PKC inhibitor. These results
indicated that intracellular signaling pathways of cAMP and PKC modulate
free radical-mediated nephrotoxicity induced by CER.
Keywords: Cephaloridine, Nephrotoxicity, Free radical, cAMP, Phorbol
myristate acetate
Copyright The Japanese Pharmacological Society
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