Sakaguchi K, Akahori F, Shirai M, Masaoka T, Arishima K, Kounenis G
College of Environmental Health, Azabu University, Kanagawa, Japan.
Vet Hum Toxicol. 1998 Apr;40(2):77-82.
H2-receptor antagonists inhibit cholinesterase (ChE) activity. We examined perturbations in ChE isoenzyme patterns and ChE activities of rats from the combined effects of fenthion (FEN) and cimetidine (CIM). Sixty-four female Sprague-Dawley rats were divided into 8 groups. Four rat groups were given FEN or gum arabic solution and each group divided into 2 small groups according to the CIM or gum arabic administration. FEN was administered po at 12.3 mg/kg (1/20 LD50) or 24.5 mg/kg (1/10 LD50) for 14 days or 49 mg/kg (1/5 LD50) every 4 days. CIM was given po at 1,500 mg/kg from days 7 to 13. Samples were collected 3 h after CIM administration on days 8 and 13. CIM did not influence ChE isoenzyme patterns or ChE activity. FEN inhibited both the ChE isoenzyme patterns and ChE activities without producing clinical signs. Although 1 rat in the 12.5 mg FEN/kg + CIM group died on day 10, all rats in other FEN (24.5 mg/kg or 49 mg/kg) + CIM groups died on days 8-10. Differences in suppression of ChE isoenzyme patterns were detectable between the FEN-dosed and FEN + CIM-dosed groups. There were no differences in ChE activities between the FEN-dosed and FEN + CIM-dosed groups. The i.p. administration of 500 mg CIM/kg (LD50) did not suppress ChE activities.
H2受体拮抗剂可抑制胆碱酯酶(ChE)活性。我们研究了倍硫磷(FEN)与西咪替丁(CIM)联合作用对大鼠ChE同工酶模式及ChE活性的影响。将64只雌性Sprague-Dawley大鼠分为8组。4组大鼠给予FEN或阿拉伯树胶水溶液,每组再根据是否给予CIM或阿拉伯树胶水溶液分为2个小组。FEN经口给药,剂量分别为12.3 mg/kg(1/20半数致死量)或24.5 mg/kg(1/10半数致死量),连续给药14天,或每4天给药49 mg/kg(1/5半数致死量)。从第7天至第13天,CIM经口给药剂量为1500 mg/kg。在第8天和第13天,于给予CIM 3小时后采集样本。CIM不影响ChE同工酶模式或ChE活性。FEN可抑制ChE同工酶模式及ChE活性,且未产生临床症状。虽然12.5 mg FEN/kg + CIM组有1只大鼠在第10天死亡,但其他FEN(24.5 mg/kg或49 mg/kg)+ CIM组的所有大鼠均在第8 - 10天死亡。FEN给药组与FEN + CIM给药组在ChE同工酶模式抑制方面存在差异。FEN给药组与FEN + CIM给药组在ChE活性方面无差异。腹腔注射500 mg CIM/kg(半数致死量)不抑制ChE活性。