ISSN 1062-3590, Biology Bulletin, 2007, Vol. 34, No. 3, pp. 267–270. © Pleiades Publishing, Inc., 2007. Original Russian Text © I.K. Svanidze, D.P. Museridze, E.V. Didimova, N.N. Gvinadze, L.G. Gegenava, I.A. Bregvadze, 2007, published in Izvestiya Akademii Nauk, Seriya Biologicheskaya, 2007, No. 3, pp. 325–328.
ANIMAL AND HUMAN PHYSIOLOGY
Correction of Changes Induced by Toluene in the Cortical and Subcortical Structures of Albino Rat Brain I. K. Svanidze, D. P. Museridze, E. V. Didimova, N. N. Gvinadze, L. G. Gegenava, and I. A. Bregvadze Beritashvili Institute of Physiology, ul. Gotua 14, Tbilisi, 380060 Georgia e-mail:
[email protected] Received April 20, 2006
Abstract—The number and weight of cells in the cortical and subcortical structures of the cerebral and cerebellar motor system in albino rats after a long-term exposure to toluene were determined. Toluene intoxication proved to kill projection neurons and interneurons in the sensorimotor cortex, ventrolateral thalamic nucleus, caudate nucleus, pallidum, red nucleus, and inferior olivary complex. The decreased number of cerebellar cells was mediated by atrophic changes as indicated by the decrease in the area and dry weight of Purkinje cells. The addition of plaferon LB to the diet attenuated the cytotoxic effect of toluene. DOI: 10.1134/S1062359007030089
Investigation of toluene effect on animal and human body can be interesting for neurobiology and general ecology, since toluene is present in urban atmosphere, since it is a component of exhaust and other products of oil transformation. This organic solvent is a hallucinogen and a drug of abuse. It is important to understand the effect of toluene on cells of the central nervous system, since toluene vapors are known to affect the development of cerebral structures (Gospe and Zhou, 2000; Saavedra et al., 1996). Chronic toluene intoxication induced considerable injury in prefrontal cortical neurons, cerebellar Purkinje cells, neurons of the hippocampal fields (Korbo et al., 1996), and astrocytes of the hippocampal dentate gyrus (Fukui et al., 1996). The destructive processes in the motor system induced neuronal atrophy (Kamran et al., 1998). The number of neurons proved to decrease in the cortical and subcortical structures of the motor system during early ontogeny (Museridze et al., 2004) and in the olfactory bulbs after prenatal and postnatal intoxication (Dzhaparidze et al., 2003). Toluene metabolism leads to the accumulation of free radicals in the body (Nakai et al., 2003) and their tissue concentration remains stable after the blood concentration of toluene decreases. High level of free radicals is observed in the central nervous system, in particular in the hippocampus (Baydas et al., 2003). Toluene vapor intoxication affects immune system activity (Matheson et al., 2005). Plaferon (placental interferon) is an analog of leukocyte interferon; it has immunomodulating and antihypoxic activities and stimulates the recovery from injuries and various pathologies (Chkhikvishvili et al., 1995; Metreveli and Bakhutashvili, 1995). Plaferon also proved to have neurotrophic properties (Sirovskii et al., 1995; Mikeladze et al., 1995; Mitagvariya et al., 1996).
We studied the effect of toluene on neurons in the cortical and subcortical structures of the motor system and cerebellum in albino rats as well as possible correction of these changes by plaferon LB. MATERIALS AND METHODS The effect of toluene on the sensorimotor cortex, ventrolateral thalamic nucleus, caudate nucleus, pallidum, red nucleus, principal nucleus of the inferior olivary complex, and cerebellum was studied in albino rats of different age. The control and experimental groups included rats at the age of 2–3 months housed in uniform plastic cages with four individuals per cage and fed pelletized and natural chow. They were kept under normal room light conditions with a free access to water. In the experiments on the toluene effect on the brain, onemonth-old rats were exposed to toluene vapors in a desiccator (Gospe and Zhou, 2000) for 15 min five times a week for one or two months. In two experiments, rats received 0.2 mg/kg plaferon as a food supplement prior to inhalation (Mitagvaria et al., 2001). In total, the brain of 24 animals was studied, four animals in each group. The brain was fixed in Carnoy’s fluid. Paraffin sections (10 µm) were stained with cresyl violet. The neuron numbers were counted using an ocular grid, the area of which was 0.256 µm2 for 7× ocular and 40× objective lens. Forty fields of view were examined for each brain structure. The degree of Purkinje cell atrophy was evaluated from the area and dry weight of 100 neurons after a one-month intoxication, when cell death was most pronounced. Dry weight (cell weight) was determined using the homogeneous field method on an interference microscope MPI-5. The studied cerebral
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Number of neurons in the cortical and subcortical structures of the rat brain after toluene intoxication and plaferon LB administration Two-month-old animals
Three-month-old animals
Cerebral part Sensorimotor cortex Thalamus Caudate nucleus Pallidum Red nucleus Olivary complex Cerebellum
control
toluene
toluene + plaferon
control
toluene
toluene + plaferon
50.2 ± 1.1
34.2 ± 1.1
47.3 ± 1.4
50.8 ± 0.8
21.7 ± 0.7
29.2 ± 0.9
P < 0.01
P < 0.05
P < 0.01
P < 0.01
35.1 ± 1.4
53.6 ± 1.1
41.9 ± 1.0
57.3 ± 1.6
P < 0.01
P < 0.01
P < 0.01
P < 0.01
82.5 ± 2.8
104.1 ± 1.5
90.5 ± 1.5
96.7 ± 1.1
P < 0.01
insignificant
P < 0.01
insignificant
27.7 ± 1.0
46.3 ± 1.0
46.2 ± 0.9
49.7 ± 1.0
P < 0.01
P < 0.01
P < 0.01
insignificant
16.3 ± 0.5
19.4 ± 0.6
20.1 ± 0.4
25.4 ± 0.4
P < 0.01
insignificant
P
