1-2-linoleoylphosphatidylcholine and Liver-Diseases--Alcoholic

Topics: Animals; Dietary Fats; Ethanol; Humans; In Vitro Techniques; Liver; Liver Diseases, Alcoholic; Phosphatidylcholines

Chronic ethanol consumption depletes phosphatidylcholines (PC) in membranes and hepatic mitochondria are an early target of this toxicity. Our previous studies showed that soybean-derived polyenylphosphatidylcholine (PPC), attenuated mitochondrial liver injury. Since dilinoleoylphosphatidylcholine (DLPC) is the major component of PPC, we assessed whether it is responsible for the protection of PPC. Forty-two male rats were fed the following liquid diets for 8 weeks: Control; Control with DLPC (1.5 g/1000 Calories (Cal); Alcohol (36% of Cal); Alcohol with DLPC (1.5 g/1000 Cal) and Alcohol with PPC (3 g/1000 Cal). As expected, ethanol feeding diminished the capacity of hepatic mitochondria to oxidize glutamate and palmitoyl-1-carnitine, and also decreased the activity of mitochondrial cytochrome oxidase. These effects were equally prevented by either PPC or DLPC. In conclusion, DLPC fully reproduced PPC's protective action and may be effective in the prevention or delay of more severe liver damage.

Topics: Animals; Cell Respiration; Electron Transport Complex IV; Ethanol; Fatty Acids; Liver Diseases, Alcoholic; Male; Mitochondria, Liver; Oxidation-Reduction; Phosphatidylcholines; Rats

Cytochrome P4502E1 (CYP2E1) induction by ethanol contributes to alcoholic liver disease and we found that a mixture of polyunsaturated phosphatidylcholines (PPC), which protects against alcohol-induced liver injury, also decreases CYP2E1. Since dilinoleoylphosphatidylcholine (DLPC) is the major component of PPC, we assessed here whether it is responsible for the protection of PPC by feeding rats for 8 weeks our liquid diet containing ethanol (36% of energy) or isocaloric carbohydrates, with either DLPC (1.5 g/1000 cal), PPC (3 g/1000 cal), or linoleate. CYP2E1 was assessed by Western blots and by two of its enzyme activities: the microsomal ethanol-oxidizing system (MEOS) and p-nitrophenolhydroxylase (PNP). With ethanol, CYP2E1 increased 10-fold, with corresponding rises in PNP and MEOS activities. Compared to linoleate, DLPC significantly decreased cytochrome b(5), total cytochromes P450, CYP2E1 content and its corresponding activities. DLPC decreases ethanol-induced CYP2E1 and should be considered for the prevention of alcoholic liver disease.

Topics: Animals; Blotting, Western; Body Weight; Cytochrome P-450 CYP2E1; Cytochromes b5; Diet; Down-Regulation; Enzyme Induction; Ethanol; Linoleic Acid; Liver; Liver Diseases, Alcoholic; Male; Microsomes, Liver; Organ Size; Phosphatidylcholines; Rats; Rats, Sprague-Dawley

Polyenylphosphatidylcholine (PPC), a mixture of polyunsaturated phosphatidylcholines extracted from soybeans, protects against alcoholic and non-alcoholic liver injury. Because Kupffer cells mediate liver injury, we hypothesized that PPC may modulate their activation. The activation of Kupffer cells by lipopolysaccharide (LPS) leads to an enhanced production of cytokines. Among these, tumor necrosis factor-alpha(TNF-alpha) exerts mainly a hepatotoxic effect, whereas interleukin-1beta (IL-1beta) appears to be hepatoprotective. The present study evaluated whether dilinoleoylphosphatidylcholine (DLPC), the main component of PPC (40% to 52%), affects LPS-induced Kupffer cell activation in vitro. For comparison, palmitoyl-linoleoylphosphatidylcholine (PLPC), the other major component of PPC (23% to 24%), and distearoylphosphatidylcholine (DSPC), the saturated counterpart of DLPC, were also tested. Rat Kupffer cells were cultured in serum-free RPMI-1640 medium containing 10 micromol/L of either DLPC, PLPC, or DSPC in the presence or absence of LPS (1 microg/mL). After 20 hours in culture, the media were collected for cytokine measurements by enzyme-linked immunosorbent assays. LPS significantly stimulated TNF-alpha and IL-1beta production by 62% and 328%, respectively. Treatment of Kupffer cells with LPS plus DLPC decreased the production of TNF-alpha by 23% (12.17+/-1.83 pg/ng DNA vs 15.72 +/-2.74 pg/ng DNA, P < .05, n = 6) and increased that of IL-1beta by 17% (1.80 +/- 0.16 pg/ng DNA vs 1.54 +/- 0.08 pg/ng DNA, P< .05, n = 6). No effect of PLPC or DSPC on LPS-induced TNF-alpha or IL-1beta generation was observed, thereby illustrating the selective effect of DLPC in this process. Thus DLPC selectively modulates the LPS-induced activation of Kupffer cells by decreasing the production of the cytotoxic TNF-alpha while increasing that of the protective IL-1beta. This dual action of DLPC on cytokines may provide a mechanism for the protective effect against liver injury, but its significance still needs to be determined by in vivo studies.

Topics: Animals; Cytokines; In Vitro Techniques; Interleukin-1; Kupffer Cells; Lipopolysaccharides; Liver; Liver Diseases, Alcoholic; Male; Phosphatidylcholines; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha