Ariyoshi T, Eguchi M, Muraki Y, Yasumatsu H, Suetsugu N, Arizono K
J Pharmacobiodyn. 1981 Jan;4(1):69-76. doi: 10.1248/bpb1978.4.69.
Effects of chlorinated benzenes on the activities of delta-aminolevulinic acid (delta-ALA) synthetase and heme oxygenase, the rate-limiting enzyme in heme biosynthesis and degradation respectively, and on the incorporation of 3H-delta-ALA into hemoprotein in the liver of male rats were investigated. Monochlorobenzene (MCB) and 1,2,4-trichlorobenzene(TRCB) stimulated significantly the activities of above both hepatic enzymes. After a single injection of 200 mg/kg, heme oxygenase activity was enhanced rapidly and sustained markedly for at least 48 hr by MCB treatment, while that was also enhanced but restored nearly to control levels at 48 hr by TRCB. delta-ALA synthetase activity was once decreased at 6 hr and restored within 12 hr and then reached peak levels (about 2--3 times to control levels) at 24 hr by MCB or TRCB treatment. However, this activity was sustained for 48 hr by TRCB treatment, whereas returned again to nearly control levels by MCB at 48 hr. Cytochrome P-450 content at 48 hr was significantly decreased by MCB (63% to control), in contrast, increased by TRCB (200% to control). When MCB or TRCB injected once daily throughout the study, biphasic disappearance of radioactivity incorporated into CO-binding particles was shown in control and MCB- or TRCB-treated rats. The half-life of the fast phase was about 8 hr in control and about 6 or 13 hr in MCB- or TRCB-treated rats respectively.
研究了氯苯对雄性大鼠肝脏中δ-氨基乙酰丙酸(δ-ALA)合成酶和血红素加氧酶活性的影响,这两种酶分别是血红素生物合成和降解中的限速酶,同时还研究了氯苯对3H-δ-ALA掺入肝血红蛋白的影响。一氯苯(MCB)和1,2,4-三氯苯(TRCB)显著刺激了上述两种肝脏酶的活性。单次注射200mg/kg后,MCB处理可使血红素加氧酶活性迅速增强,并至少持续显著增强48小时,而TRCB处理也可使其增强,但在48小时时几乎恢复到对照水平。MCB或TRCB处理后,δ-ALA合成酶活性在6小时时一度下降,12小时内恢复,然后在24小时时达到峰值水平(约为对照水平的2 - 3倍)。然而,TRCB处理可使该活性持续48小时,而MCB处理在48小时时又再次恢复到接近对照水平。48小时时,MCB可使细胞色素P - 450含量显著降低(降至对照的63%),相比之下,TRCB可使其增加(增至对照的200%)。在整个研究过程中,每天注射一次MCB或TRCB,对照大鼠以及经MCB或TRCB处理的大鼠体内,掺入CO结合颗粒中的放射性呈现双相消失。快速相的半衰期在对照大鼠中约为8小时,在经MCB或TRCB处理的大鼠中分别约为6小时或13小时。