Billi de Catabbi S, Sterin-Speziale N, Fernandez M C, Minutolo C, Aldonatti C, San Martín de Viale L
Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Int J Biochem Cell Biol. 1997 Feb;29(2):335-44. doi: 10.1016/s1357-2725(96)00096-9.
A great deal of information concerning the effects of hexachlorobenzene on the haem metabolic pathway has been obtained but little is known about the effects of the drug on lipid metabolism. Consequently, the time course of phospholipid metabolism alteration caused by this xenobiotic was evaluated as related to changes in porphyrin metabolism with the aim to understand better the interregulation of both metabolisms. Female Wistar rats were treated with HCB (1 g/kg) over a 1-8 week period. Individual phospholipid content, [32P] incorporation, total lipid content, lipid peroxidation, uroporphyrinogen decarboxylase activity, its inhibitor generation and porphyrin content, were the parameters measured in the liver of treated rats. Phospholipid metabolism-with the exception of sphingomyelin-presents a biphasic behaviour, in both the endogenous contents and de novo synthesis. The turning point between both phases is the time at which levels of porphyrin and conjugated dienes increase, the latter compounds being involved in oxidative processes. On the other hand, sphingomyelin decreases continuously during the 8 weeks of treatment. It was also found that the malondialdehyde content increased during the early stages. The time sequence for haem metabolism parameters showed that the accumulation of porphyrins occurs after the decrease in uroporphyrinogen decarboxylase activity and the enzyme inhibitor formation, which are early events (first and second weeks). Porphyrins could not by themselves exacerbate uroporphyrinogen decarboxylase impairment or inhibitor generation. This study shows that hexachlorobenzene alters simultaneously phospholipid and porphyrin metabolisms from the early stages, and generates an oxidative environment that favours porphyrinogens and lipid oxidation at later stages. So, this oxidative environment links the alterations on both metabolisms.
关于六氯苯对血红素代谢途径的影响已获得大量信息，但对于该药物对脂质代谢的影响却知之甚少。因此，评估了这种外源性物质引起的磷脂代谢改变的时间进程，并将其与卟啉代谢的变化相关联，目的是更好地理解这两种代谢之间的相互调节。在1 - 8周的时间内，用六氯苯（1克/千克）对雌性Wistar大鼠进行处理。测量了处理大鼠肝脏中的个体磷脂含量、[32P]掺入量、总脂质含量、脂质过氧化、尿卟啉原脱羧酶活性、其抑制剂生成以及卟啉含量等参数。除鞘磷脂外，磷脂代谢在内源含量和从头合成方面均呈现双相行为。两个阶段之间的转折点是卟啉和共轭二烯水平增加的时间，后者参与氧化过程。另一方面，在8周的处理过程中，鞘磷脂持续减少。还发现丙二醛含量在早期阶段增加。血红素代谢参数的时间序列表明，卟啉的积累发生在尿卟啉原脱羧酶活性降低和酶抑制剂形成之后，而这两者是早期事件（第一周和第二周）。卟啉本身并不会加剧尿卟啉原脱羧酶的损伤或抑制剂的生成。这项研究表明，六氯苯从早期阶段就同时改变磷脂和卟啉代谢，并产生一种氧化环境，在后期有利于卟啉原和脂质氧化。因此，这种氧化环境将两种代谢的改变联系起来。
