Involvement of oxidative stress in bee venom-induced inhibition of Na+/glucose cotransporter in renal proximal tubule cells.

1. The present study was conducted to examine the involvement of oxidative stress in bee venom-induced inhibition of the Na + /glucose cotransporter (α-methyl-D-glucopyranoside (a-MG) uptake), a typical functional marker of proximal tubules, in primary cultured rabbit renal proximal tubule cells (PTC). 2. Bee venom (≥ 1 μg/mL) increased lipid peroxide (LPO) formation over 30 min. The increase in [ 3 H]-arachidonic acid (AA) release and LPO formation and the inhibition of α-MG uptake induced by bee venom (1 μg/mL) and melittin (a major component of bee venom; 0.5 μg/mL) were blocked by N-acetyl-L-cysteine, vitamin C and vitamin E, anti-oxidants. 3. Bee venom- and melittin-induced increases in LPO formation and inhibition of α-MG uptake were significantly prevented by mepacrine and AACOCF 3 , phospholipase A 2 inhibitors. In addition, nordihydroguaiareic acid (a lipoxygenase inhibitor) and econazole (a cytochrome P-450 epoxygenase inhibitor), but not indomethacin (a cyclo-oxygenase inhibitor), prevented bee venom- and melittin-induced increases in LPO formation and inhibition of α-MG uptake. 4. Nordihydroguaiareic acid prevented bee venom- and melittin-induced increases in Ca 2 + uptake. Moreover, anti-oxidants significantly prevented bee venom- and melittin-induced increases in Ca 2 + uptake. 5. In conclusion, bee venom inhibits α-MG uptake via the phospholipase A 2 -oxidative stress-Ca 2 + signalling cascade in primary cultured rabbit renal proximal tubule cells.