A radical scavenger, edaravone, protects canine kidneys from ischemia-reperfusion injury after 72 hours of cold preservation and autotransplantation

BACKGROUND: Cold ischemia-reperfusion (I/R) injury is a prominent cause of delayed graft function after kidney transplantation. Reactive oxygen species play a crucial role in I/R injury. Edaravone is a synthetic radical scavenger that has been used in acute stroke. Some animal experiments have revealed its beneficial effects against I/R injury, but its effects after cold preservation and transplantation of canine kidneys are unknown. METHODS: Female hybrid dogs weighing 11 to 13 kg were used. Under anesthesia, the left kidney was harvested. After 72 hr of preservation in cold histidine-tryptophan-ketoglutarate solution, autotransplantation was performed in the right iliac fossa, with contralateral nephrectomy. Animals were divided into control and treatment groups (n=6 per group). In the treatment group, edaravone was administered intravenously at harvest and at reperfusion (3 mg/kg) and in addition was added to the preservation solution (50 microM). RESULTS: Animal survival at 2 weeks was four of six in the control group and six of six in the treatment group. Compared with controls, treated animals had higher mean urine output, higher mean glomerular filtration rate, improved tubular cell function, lower mean serum creatinine, and lower renal vascular resistance. Biopsy specimens from treated animals showed less tubular cell damage and decreased P-selectin expression in endothelial cells. Lipid peroxidation of renal tissue and urinary excretion of 8-hydroxy-2'-deoxyguanosine were suppressed by the treatment. CONCLUSIONS: Edaravone reduced cold I/R injury in canine renal transplantation. The agent has the potential to ameliorate preservation injury in clinical transplantation.     

Inhibitory effects of B-HT 920 on gastric acid secretion induced by vagal stimulation in rat

Effects of B-HT 920 on the vagally stimulated gastric acid secretion were studied in anesthetized and gastric fistula rats. When the gastric acid secretion was increased by stimulation of the vagus nerve, B-HT 920 significantly inhibited the vagally induced gastric acid secretion. This inhibitory effect of B-HT 920 was partially attenuated by prazosin, α₁-adrenoceptor antagonist and virtually abolished by yohimbine, α₂-adrenoceptor antagonist. On the other hand, when the gastric acid secretion was increased by the infusion of bethanechol, a muscarinic parasympathetic stimulant, B-HT 920 had no effect on the bethanechol-induced gastric acid secretion. These results suggest that B-HT 920 inhibits vagally induced gastric acid secretion by activation of presynaptic α-adrenoceptors located on the vagally stimulated pathways in the gastric wall and this effect of B-HT 920 is more related to α₁-adrenoceptors than α₁-adrenoceptors.     

低水平~(60)Co-γ射线全身照射诱导家兔外周血淋巴细胞的遗传学适应性反应研究

用~(60)Co-γ射线对家兔进行慢性全身均匀照射,当累积剂量分别达到0.3、0.75、0.9、1.2、1.5、1.8Gy时,取外周血G_o期和G_2期淋巴细胞,再均以1.5Gy X射线照射。制备染色体标木观察有无适应性反应及其剂量范围。结果证明D_1+D_2(G_o期)组,D_1在0.3～1.5Gy之间;D_1+D_2(G_2期)组D_1在0.3～1.2Gy剂量范围内均可诱导出明显地适应性反应。     

DNA存在下Cu(Ⅱ)—去甲斑螫酸络合物催化抗坏血酸氧化的动力学

在pH 7.40,20.00±0.05℃,磷酸盐缓冲液中,研究了Cu(Ⅱ)及Cu(Ⅱ)络合物的可见光谱,以及DNA存在下,Cu(Ⅱ)的去甲斑蝥酸络合物Cu(Ⅱ)/H_2DCA催化抗坏血酸(H_2A)有氧氧化动力学,检测了Cu(Ⅱ)/H_2DCA催化H_2A有氧氧化过程中·OH生成的速度。实验结果表明,在Cu(Ⅱ)/H_2DCA存在下,抗坏血酸断裂DNA链的反应体系中,存在Cu(Ⅱ)与H_2DCA和DNA的三元络合。据此,推测H_2A的催化有氧氧化对DNA链的断裂作用按特定部位的Fenton反应机理进行。该机理能够解释前文的DNA链断裂实验的所有结果。     

铜(Ⅱ)—去甲斑蝥酸络合物存在下抗环血酸对DNA链的断裂作用

本文在pH 7.40,37℃磷酸盐缓冲体系中,研究了铜(Ⅱ)的去甲斑蝥酸络合物(Cu(Ⅱ)/H_2DCA)存在下,不同因素对抗坏血酸(H_2A)断裂DNA链的影响。实验结果表明,Cu(Ⅱ)/H_2DCA催化抗坏血酸有氧氧化过程中产生的H_2O_2进一步发生Fenton反应,生成的·OH是抗坏血酸断裂DNA链的真正物种。但简单的Fenton反应不能解释本实验的所有结果。     

叶绿素衍生物在犬膀胱粘膜内代谢的研究

目的：为了了解叶绿素衍生物（ＣＰＤ４）口服后在膀胱粘膜内含量变化的状况，以便为临床应用提供实验依据。方法：１３条实验犬分为３个不同剂量组，应用荧光检测法作服药后不同时段膀胱粘膜ＣＰＤ４含量的测定。结果：ＣＰＤ４用于实验犬的合适剂量是１００ｍｇ／ｋｇ，明显低于此值将显著影响组织的吸收，从而降低光动力作用。在禁食组中，组织内吸收的最高峰值出现在服药后２ｈ，而进食组却推迟出现在服药后６￣１２ｈ。结论：为