The effects of the 21-aminosteroid U-74389G on spatial orientation in rats after a cerebral oligemic episode and iron-induced oxidative stress

Abstract

Oligemic episodes and increased iron concentration have both been proposed as being involved in neurodegenerative diseases. In animal models, a combination of both of these might therefore mimic the clinical pathology in humans. In rats, intrastriatal injections of ferric chloride, FeCl3, one week after a 60-minute oligemic episode, produced by bilateral clamping of the carotid arteries under pentobarbital anaesthesia (BCCA) impaired the animals' learning ability in a water maze task. Median adult rats, after intrastriatal 0.3 microg FeCl3, are impaired when challenged during the first three trial blocks, while after 0.06 microg FeCl3, an impairment is seen during the process of habituation to the challenge. Two-year-old animals do not show any learning effect at all after the combination of BCCA and intrastriatal FeCl3. Lazaroid U-74389G, a potent inhibitor of iron-induced lipid peroxidation, totally prevents the learning impairments in both median adult and aged animals, suggesting that iron-induced lipid peroxidation may be responsible for the late learning deficiencies. However, when U-74389G is applied one week after the oligemic episode but without the additional injection of iron, U-74389G on its own also impairs the animals' learning ability. The present animal model, when applied to clinical studies of lazaroids in humans, does seem able to give reliable information concerning the neuroprotective properties of such drugs.

Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet

“…Whether lazaroid crosses the placenta is unknown, but the latter cited study among others indicates it crosses the bloodbrain barrier (14,25). Our results suggest that either low-level oxidative stress is ongoing during gestation which could cause or be concomitant with reduced antioxidant defenses and is partially prevented by lazaroid (see below), or alternatively, that lazaroid is still present in the newborn tissues and helps prevent oxidative insult associated with increase in PO 2 at birth.…”

The Effect of the Antioxidant Drug “U-74389g” on Uterus Congestion During Ischemia Reperfusion Injury in Rats

“…Horáková L et al, [16] calculated the preventive effect concerning lipid peroxidation at 160 IC50 μmol/l by U 74389G in oxidative stress. Heim C et al, totally prevented [17] the learning impairments, suggesting that lipid peroxidation may be responsible for the late learning deficiencies. Vlkolinský R revealed [18] protective activity on Synaptic Transmission (ST) recovery and on t 1/2 during hypoxia; a protective potency of U-74389G on Population Spikes (PoS) recovery and a possibility to delay the early ST decay during hypoxia, which might indicate improved energetic state of neurons in the treated tissue.…”

The Effect of the Antioxidant Drug U-74389G on Magnesium Levels During Hypoxia–Reoxygenation Injury in Rats

“…Heim и соавт. [15] установили нарушение способности к обучению спустя 1 нед после 60-минутного олигемического эпизода ишемии-реперфузии среднего отдела головного мозга взрослых крыс с помощью инъекций дозой 0,3 либо 0,06 мкг хлорида железа (FeCl 3 ). Лазароид U-74389G, мощный ингибитор железоиндуцируемого перекисного окисления липидов, полностью предотвращает нарушения функций обучения животных как среднего возраста, так и старых.…”