The correlation between lipid peroxidation in different brain regions and the severity of lindane-induced seizures in rats.

The aim of this study was to investigate the dynamics of lipid peroxidation and the possible correlation between lipid peroxidation in different brain regions and behavioral manifestations in lindane-induced seizures in rats. Male Wistar rats were divided into the following groups: 1. control, saline-treated group; 2. dimethylsulfoxide (DMSO)-treated group; 3. lindane-treated group (8 mg/kg), intraperitoneally. Animals were sacrificed 0.5 or 4 h after treatment and the malondialdehyde level and superoxide dismutase (SOD) activity were determined in various brain regions spectrophotometrically. Behavioral changes were classified according to the descriptive scale (0--no response, 1--head nodding, lower jaw twitching; 2--myoclonic body jerks, bilateral forelimb clonus with full rearing; 3--progression to generalized clonic convulsions followed by tonic extension of fore- and hind limbs and tail; 4--status epilepticus). A significant rise in the malondialdehyde level was detected in the cerebral cortex, hippocampus, and thalamus of lindane-treated animals 0.5 and 4 h after administration (P < 0.05). SOD activity (total and mitochondrial) was significantly decreased in the hippocampus and the cortex of lindane-treated animals at both time points (P < 0.05). An initial fall in SOD activity was detected in the thalamus 4 h after lindane administration (P < 0.05). A positive correlation between seizure severity and the malondialdehyde level was found in the hippocampus at both time points (P < 0.01). These results suggest that lipid peroxidation may contribute to the neurotoxic effects of lindane in early acute lindane intoxication and that behavioral manifestations correlate with lipid peroxidation in the hippocampus of lindane-treated rats.

Mechanism of 3-deazaguanine transport in the rat heart.

The aim of this study was to determine the mechanism of transport of 3-deazaguanine in the rat heart. We used single-pass, paired-tracer dilution method on isolated and retrogradely perfused rat hearts. The maximal cellular uptake (Umax) and total cellular uptake (Utot) of 3-deazaguanine were determined under control conditions and under influence of possible modifiers. Both Umax and Utot were significantly reduced in the presence of unlabeled 3-deazaguanine (from 19.57 +/- 2.02% to 8.14 +/- 1.19% and from 16.49 +/- 3.65% to 4.70 +/- 1.96%, n=6, respectively). The presence of pyrimidine nucleoside thymidine caused the reduction of both Umax and Utot (from 20.03 +/- 3.76% to 13.58 +/- 3.16% and from 16.43 +/- 3.58% to 11.94 +/- 3.13%, n=6, respectively). Also, we tested the effect of the absence of sodium ions in perfusion solution (both Umax and Utot, significantly reduced from 17.95 +/- 2.73% to 16.67 +/- 2.16% and from 16.68 +/- 2.97% to 14.81 +/- 3.04%, n=6, respectively) and the effect of dinitrophenol (both Umax and Utot significantly reduced from 19.09 +/- 3.68% to 10.58 +/- 3.14% and from 16.86 +/- 3.84% to 7.10 +/- 3.11%, n=6, respectively). The results of self- and cross-inhibition studies show that the transport of 3-deazaguanine is saturable, energy- and sodium-dependent and that 3-deazaguanine uses endogenous transport systems for thymidine and adenosine for its own transport.

Transport of endogenous nucleosides in guinea pig heart.

The purpose of this study was to investigate the characteristics of transport of endogenous nucleosides into cardiac tissue from coronary circulation. The study was performed on the isolated perfused guinea pig heart, using the rapid paired tracers single-pass technique. The maximal cellular uptake (U(max)) and total cellular uptake (U(tot)) of adenosine, deoxyadenosine, thymidine, uridine, and cytidine were determined. The cellular uptake of adenosine was significantly higher than the cellular uptake of other studied nucleosides. To elucidate the mechanisms of nucleoside transport, competition studies were performed and the influence of S-(p-nitrobenzyl)-6-thioinosine (NBTI) and sodium ion absence on U(max) and U(tot) was investigated. Self- and cross-inhibition studies indicated the saturable mechanism of nucleosides transport into cardiac tissue and the involvement of different transport mechanisms for purine and pyrimidine nucleosides. The study also showed that both equilibrative-sensitive (es) and sodium-dependent transport were responsible for adenosine and thymidine cellular uptake.