Effects of Ro 31-8220 on lipopolysaccharides-induced hepatotoxicity and release of tumor necrosis factor from rat Kupffer cells
Abstract
AIM: To investigate protein kinase C (PKC) functions on lipopolysaccharide
(LPS)-induced hepatotoxicity, a new potent PKC inhibitor Ro 31-8220 (Ro) was used
to detect its effect on LPS-induced hepatotoxicity in rat hepatocytes and tumor
necrosis factor (TNF) release from rat Kupffer cells (KC).
METHODS: Hepatocytes (containing KC) were incubated with LPS (10 mg.L-1) and Ro
(0.1-10 mumol.L-1) for 24 h, alanine aminotransferase (AlaA) leakage in the
culture as indication of hepatotoxicity. The TNF activity in the supernatant of
rat KC culture with LPS in the presence of Ro (0.1-10 mumol.L-1) was monitored by
the L929 target cell lytic assay.
RESULTS: Ro (0.1-10 mumol.L-1) reduced AlaA leakage in the hepatocyte culture. Ro
inhibited dose-dependently the LPS-induced TNF production from rat KC.
CONCLUSION: PKC inhibitor Ro protects the hepatocytes from LPS-induced
cytotoxicity and inhibits the LPS-induced TNF production from rat KC.
Keywords:
(LPS)-induced hepatotoxicity, a new potent PKC inhibitor Ro 31-8220 (Ro) was used
to detect its effect on LPS-induced hepatotoxicity in rat hepatocytes and tumor
necrosis factor (TNF) release from rat Kupffer cells (KC).
METHODS: Hepatocytes (containing KC) were incubated with LPS (10 mg.L-1) and Ro
(0.1-10 mumol.L-1) for 24 h, alanine aminotransferase (AlaA) leakage in the
culture as indication of hepatotoxicity. The TNF activity in the supernatant of
rat KC culture with LPS in the presence of Ro (0.1-10 mumol.L-1) was monitored by
the L929 target cell lytic assay.
RESULTS: Ro (0.1-10 mumol.L-1) reduced AlaA leakage in the hepatocyte culture. Ro
inhibited dose-dependently the LPS-induced TNF production from rat KC.
CONCLUSION: PKC inhibitor Ro protects the hepatocytes from LPS-induced
cytotoxicity and inhibits the LPS-induced TNF production from rat KC.