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Involvement Of Oxidative Stress In Bee Venom‐Induced Inhibition Of Na + /Glucose Cotransporter In Renal Proximal Tubule Cells
Author(s) -
Han Ho Jan,
Park Soo Hyun,
Lee Jang Hern,
Yoon Byeong Cheol,
Park Kwon Moo,
Mar Woong Chon,
Lee Hye Jung,
Kang Sung Keel
Publication year - 2002
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2002.03685.x
Subject(s) - melittin , chemistry , epoxygenase , phospholipase a2 , biochemistry , arachidonic acid , pharmacology , oxidative stress , endocrinology , medicine , biology , enzyme , peptide
SUMMARY 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 ( α ‐MG) uptake), a typical functional marker of proximal tubules, in primary cultured rabbit renal proximal tubule cells (PTC). 2. Bee venom (≥ 1 μ g/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 μ g/mL) and melittin (a major component of bee venom; 0.5 μ g/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.