LAZAROIDS PROTECT ISOLATED RAT PANCREATIC ACINAR-CELLS AGAINST DAMAGE-INDUCED BY FREE-RADICALS

被引:13
|
作者
NIEDERAU, C [1 ]
SCHULZ, HU [1 ]
KLONOWSKI, H [1 ]
机构
[1] OTTO VONGUERICKE UNIV, DEPT SURG, MAGDEBURG, GERMANY
关键词
LAZAROIDS; LIPID PEROXIDATION; FREE RADICALS; OXIDATIVE INJURY; PANCREATITIS; CELL DAMAGE; XANTHINE OXIDASE;
D O I
10.1097/00006676-199508000-00001
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Lazaroids, 21-aminosteroids without gluco-and mineralocorticoid activity, protect against oxidative injury in nervous system cells and may therefore also have a potential for treatment of pancreatitis, where oxidative stress contributes to cell injury. The present study evaluates the protective potential of the lazaroids U-78518F, U-74500A, and U-74389F against damage to isolated pancreatic acinar cells exposed to two models of oxidative stress: (a) a XOD/HX model, consisting of xanthine oxidase, hypoxanthine, and chelated FeCl3; and (b) an ADP/Fe model, consisting of FeSO4 and the reducing agent ADP. Both models caused time-dependent cell injury as assessed by uptake of trypan blue and release of lactate dehydrogenase. Short-term peak production of free radicals in the XOD/HX model-as monitored by the deoxyribose assay-was more injurious to cells than continuous radical generation at lower levels in the ADP/Fe model. In general, lazaroids at 1-10 mu M reduced oxidative damage and deoxyribose oxidation in both models.The degree of reduction of cell damage and deoxyribose oxidation depended on the type and concentration of the lazaroid and the model used. Lazaroid concentrations <0.1 mu M were ineffective, and concentrations >50 mu M even accelerated cell injury, although lazaroids still served as scavengers at high concentrations. At least part of the noxious effects of high lazaroid concentrations is due to nonspecific membrane damage because these concentrations caused cell injury also in the absence of oxidative stress. The limited range of protective concentrations has to be observed in further in vivo studies. Interestingly, acinar cells in the absence of lazaroids also reduced radical-induced deoxyribose degradation. Thus, despite its susceptibility to oxidative stress, the pancreatic acinar cell itself acts as a potent radical scavenger.
引用
收藏
页码:107 / 121
页数:15
相关论文
共 50 条
  • [21] ACETYLCHOLINE AND CHOLECYSTOKININ INDUCED ACID EXTRUSION IN MOUSE ISOLATED PANCREATIC ACINAR-CELLS AS MEASURED BY THE MICROPHYSIOMETER
    DENYER, JC
    THORN, P
    BOUNTRA, C
    JORDAN, CC
    JOURNAL OF PHYSIOLOGY-LONDON, 1993, 459 : P390 - P390
  • [22] CL- CONDUCTANCE IN ISOLATED RAT PAROTID ACINAR-CELLS IS TRIGGERED BY CYTOSOLIC FREE CALCIUM
    HASSONI, AA
    GRAY, PTA
    JOURNAL OF PHYSIOLOGY-LONDON, 1993, 459 : P349 - P349
  • [23] EFFECT OF LA3+ ON SECRETAGOGUE-INDUCED CA2+ FLUXES IN RAT ISOLATED PANCREATIC ACINAR-CELLS
    WAKASUGI, H
    STOLZE, H
    HAASE, W
    SCHULZ, I
    AMERICAN JOURNAL OF PHYSIOLOGY, 1981, 240 (04): : G281 - G289
  • [24] Phenolic compounds isolated from Dioscorea zingiberensis protect against pancreatic acinar cells necrosis induced by sodium taurocholate
    Du, Dan
    Jin, Tao
    Zhang, Rui
    Hu, Liqiang
    Xing, Zhihua
    Shi, Na
    Shen, Yan
    Gong, Meng
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (06) : 1467 - 1470
  • [25] INFLUENCE OF COLLOIDAL BISMUTH SUBCITRATE ON ENZYME-SECRETION FROM ISOLATED RAT PANCREATIC ACINAR-CELLS
    KEMMER, TP
    MALFERTHEINER, P
    BODE, G
    DITSCHUNEIT, H
    RESEARCH IN EXPERIMENTAL MEDICINE, 1992, 192 (06) : 415 - 422
  • [26] G-PROTEIN IN STIMULATION OF PI-HYDROLYSIS BY CCK IN ISOLATED RAT PANCREATIC ACINAR-CELLS
    MATOZAKI, T
    SAKAMOTO, C
    NAGAO, M
    NISHIZAKI, H
    BABA, S
    AMERICAN JOURNAL OF PHYSIOLOGY, 1988, 255 (05): : E652 - E659
  • [27] USE OF SCAVENGING OXYGEN-DERIVED FREE-RADICALS TO PROTECT THE RAT AGAINST ASPIRIN-INDUCED AND ETHANOL-INDUCED EROSIVE GASTRITIS
    SALIM, AS
    JOURNAL OF PHARMACEUTICAL SCIENCES, 1992, 81 (09) : 943 - 946
  • [28] CHOLECYSTOKININ-INDUCED PHOSPHATIDYLINOSITOL HYDROLYSIS IN RAT PANCREATIC ACINAR-CELLS - MODULATION BY EXTRACELLULAR CALCIUM AND MANGANESE
    KORC, M
    CHANDRASEKAR, B
    SIWIK, SA
    ENDOCRINOLOGY, 1991, 129 (01) : 39 - 46
  • [29] FUNCTIONAL-RAT PANCREATIC ACINAR-CELLS IN CULTURE - AN ISOLATED CELL MODEL TO STUDY REGULATED ZYMOGEN SECRETION
    ANDERSON, KL
    MILLER, LJ
    MCNIVEN, MA
    GASTROENTEROLOGY, 1993, 104 (04) : A293 - A293
  • [30] INFLUENCE OF HELICOBACTER-PYLORI PROTEINS ON ENZYME-SECRETION FROM ISOLATED RAT PANCREATIC ACINAR-CELLS
    KEMMER, TP
    NILIUS, M
    BINDER, C
    MALFERTHEINER, P
    GASTROENTEROLOGY, 1994, 106 (04) : A105 - A105