Abstract:
:Long-term intragastric administration of the antiepileptic drug sodium valproate (Vuprol Polfa) to rats for 1, 3, 6, 9 and 12 months, once daily at the effective dose of 200 mg/kg body weight showed morphological evidence of encephalopathy, manifested by numerous nonspecific changes within Purkinje cell perikarya and their dendritic processes. The first ultrastructural abnormalities appeared after 3 months. They became more severe in animals with longer survival and were most pronounced after 12 months. The changes were maintained both 1 and 3 months after drug withdrawal. Mitochondria of Purkinje cell perikarya were most severely affected. Damage to mitochondria was accompanied by disintegration and fragmentation of granular endoplasmic reticulum, dilation of channels and cisterns of Golgi apparatus, enlargement of smooth endoplasmic reticulum elements including submembranous cisterns, and accumulation of profuse lipofuscin deposits. Frequently, Purkinje cells appeared as dark ischemic neurones, with focally damaged cellular membrane and features of disintegration. Swollen Bergmann's astrocytes were seen among damaged Purkinje cells or at the site of their loss. The general pattern of submicroscopic alterations of Purkinje cell perikarya suggested severe disorders in several intercellular biochemical extents, including inhibition of oxidative phosphorylation and abnormal protein synthesis, both of which could lead to lethal damage. Ultrastructural abnormalities within dendrites were characterized by damage to elements of smooth endoplasmic reticulum, which was considerably enlarged, with formation of large vacuolar structures situated deep in the dendroplasm. Mitochondrial lesions and alterations in cytoskeletal elements--disintegration of microtubules or even their complete loss--were also observed. The general pattern of abnormalities within the organelles and cytoskeletal elements of dendritic processes in Purkinje cells in the VPA chronic experimental model imply that there are disturbances in detoxication processes. Furthermore these changes were irreversible, as they were maintained after drug withdrawal.
journal_name
Int J Exp Patholjournal_title
International journal of experimental pathologyauthors
Sobaniec-Lotowska MEdoi
10.1046/j.1365-2613.2001.00206.xsubject
Has Abstractpub_date
2001-12-01 00:00:00pages
337-48issue
6eissn
0959-9673issn
1365-2613pii
206journal_volume
82pub_type
杂志文章abstract::While the origin of tumours, whether from one cell or many, has been a source of fascination for experimental oncologists for some time, in recent years there has been a veritable explosion of information about the clonal architecture of tumours and their antecedents, stimulated, in the main, by the ready accessibilit...
journal_title:International journal of experimental pathology
pub_type: 杂志文章,评审
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abstract::Nonalcoholic steatohepatitis (NASH) is one of the life-threatening hepatic diseases; however, its pathogenesis is still unknown. To evaluate the causative role of hyperlipidaemia and high-fat diet, we compared C57BL/6 mice with inherited hyperlipidaemic model mice (LDLR(-/-)mice and ApoE(-/-) mice) fed a normal or a h...
journal_title:International journal of experimental pathology
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journal_title:International journal of experimental pathology
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journal_title:International journal of experimental pathology
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journal_title:International journal of experimental pathology
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journal_title:International journal of experimental pathology
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journal_title:International journal of experimental pathology
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journal_title:International journal of experimental pathology
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journal_title:International journal of experimental pathology
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journal_title:International journal of experimental pathology
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journal_title:International journal of experimental pathology
pub_type: 杂志文章
doi:
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journal_title:International journal of experimental pathology
pub_type: 杂志文章
doi:
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journal_title:International journal of experimental pathology
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journal_title:International journal of experimental pathology
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journal_title:International journal of experimental pathology
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journal_title:International journal of experimental pathology
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