The effects of the nephrotoxic, anticancer agents cisplatin (CDI)P) and carboplatin (CBDCA), and the free radical scavenger, stobadine, were investigated on lipid peroxidation (EI’O) of rat kidney homogenates and phosphatidylcholine (PC) liposomes. Kidney homogenates were incubated in air at 37 °C for 6-48 h and lipid peroxidation was detected spectroscopically as absorbance (533 nm) of the thiobarbituric acid- malondialdchyde (TBA-MDA) complex. CDDP (0.3-10 mmol.I'1) increased LPO of the homogenate. CBDCA decreased the TBA-MDA absorbance, yet was found to interfere with MDA, TBA and/or with the TBA-MDA complex. Thus when CBDCA is involved, the TBA- MDA method for detection of LPO is not suitable. Stobadine (0.1 mmol.I'1 ar>d 1 mmol.I1) inhibited LPO either in the control homogenate and in the homogenate where peroxidation was increased by CDDP. The effect of CDDP and CBDCA on peroxidation of PC liposomes was monitored as oxygen consumption using a Clark-type oxygen electrode. CDDP increased but CBDCA decreaed the rate of oxygen consumption during the peroxidation of liposomes induced by FcSO,». The results suggest that the effects of CDDP and CBDCA on LPO may be linked with their nephrotoxicity.
The ability of stobadine to prevent gastric mucosal injury was tested in rat gastric ischaemia induced by 30 min clamping of the coeliac artery with subsequent 30 min reperfusion. Serious injury of gastric mucosa (macroscopic and microscopic) and the increase of microvascular permeability was found after ischaemia/reperfusion in rats without stobadine. After oral pretreatment with stobadine (5 mg.kg-1, 30 min before surgery), the development of gastric mucosal lesions and changes of vascular permeability were significantly decreased.
Differential pulse voltammetry with a carbon fibre microelectrode (ME) was used in pentobarbital- anaesthetized rats for monitoring the stobadine current (STB.C) on both sides of the blood-brain barrier (BBB) in the arterial bloodstream (BS) and in the corpus striatum (CS). The STB.C exhibited a distinct peak at a polarization voltage 540±30 mV (n=4). The maximum of STB.C in BS attained 2-3 min after the STB administration (2.8 mg/100 g in 1.0 ml saline solution i.a.) was followed by a rapid decrease to about 20 % within next 3 min. The STB readily passed across the BBB: the STB.C peak appeared in the CS in the 3rd minute and continued to rise up to the 30th min. The administration of STB did not prevent a large increase (1347±326 %, n=3) of the catechol-oxidative current (CA.OC) occurring in the CS between the 4th and 5th minute after cardiac arrest. However, a decrease of ME sensitivity to CA.OC in the presence of STB was observed. This fact leads to the speculation whether a similar "quenching" of dopamine by STB could not participate in the protective effects of STB observed in the brain exposed to hypoxia-reoxygenation.