Effects of exogenous leukotrienes B4 and C4 on the viability of cultured rat hepatocytes.
Leukotrienes (LTs) are thought to be extensively involved in a liver damage in vivo through different mechanisms. In this study we used different doses (10(-7)-10(-12) M) of the dehydroxilated LTB4 and the cysteinyl LTC4 to estimate their direct injurious effects on cultured rat hepatocytes (HC). Our experiments demonstrated that exogenous LTB4 and LTC4 caused a rapid and transient increase in alanine aminotransferase release from HC and a slight, but significant decrease of mitochondrial electron transport chain activity in HC. Significant increases in ALT release were observed with LTs doses as low as 10(-12) M, but the loss of mitochondrial function was significant only at the two higher doses (10(-7) and 10(-8) M). HC were treated with the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) to inhibit the possible synthesis of endogenous LTs. The effects of exogenous LTB4 and LTC4 on NDGA-treated HC tended to be similar to those indicated in the absence of inhibitor, but were more pronounced. These data suggest that LTs may be involved in the direct damage of liver cells under pathological conditions associated with enhanced LTs formation.
Makogon
N V
NV
Department of Immunology, Bogomoletz Institute of Physiology, Ukrainian Academy of Sciences, Kiev. imm@serv.biph.kiev.ua
Korneitchuk
A N
AN
Lushnikova
I V
IV
Alexeyeva
I N
IN
D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005562:Formazans; D022781:Hepatocytes / Q000187:drug effects*; D007975:Leukotriene B4 / Q000633:toxicity*; D017997:Leukotriene C4 / Q000633:toxicity*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol; D051381:Rats; D013778:Tetrazolium Salts; D013997:Time Factors
D005562:Formazans; D016859:Lipoxygenase Inhibitors; D013778:Tetrazolium Salts; D007975:Leukotriene B4; C079782:MTT formazan; D017997:Leukotriene C4; D009637:Masoprocol; D000410:Alanine Transaminase