Phenytoin-induced Toxicity in the Postnatal Developing Cerebellum of Wistar Rats, Effect of Calotropis procera on Histomorphometric Parameters

Imosemi, I. O.; Osinubi, AA

doi:10.4067/s0717-95022011000200004

Cited by 8 publications

(8 citation statements)

References 26 publications

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“…Calotropis procera leaf extract has been reported to posses antioxidant activity by increasing the glutathione levels and decreasing the rate at which lipid peroxidation occurred in the developing cerebellum (Imosemi et al, 2010), preventing delayed maturation of cells of the cerebellar cortex and depletion of Purkinje cells of the developing cerebellum in phenytoin-induced oxidative stress (Imosemi & Osinubi, 2011). And that the antioxidant property of Calotropis procera was comparable to standard antioxidants, vitamins C and E.…”

Section: Introductionmentioning

confidence: 78%

The Role of Antioxidants in Cerebellar Development: A Review of Literature

Imosemi¹

2013

Int. J. Morphol.

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SUMMARY: Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reacting oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction, and that the embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk. ROS can oxidize molecular targets such as DNA, protein, lipid in a process called oxidative stress resulting in cellular dysfunction and in utero death or teratogenicity. This review, consisting of literature search of journals and chapters in books aims at highlighting the importance of the cerebellum in controlling various motor activities in the body, as well as substances affecting cerebellar development with a view of providing an insight to the role antioxidants play in cerebellar development. It is interesting to note that the developing brain (especially the cerebellum, cerebrum and hippocampus) is highly vulnerable to the deleterious effects of ROS. Studies have shown that exposure to oxidants in the first trimester is associated with an increased risk of major congenital anomalies, as most vital organs in the body develop and some become functional within this period in offspring. Antioxidants may prevent oxidative damage in degenerative diseases including ageing, cardiovascular diseases, cancer, Alzheimer's disease, stroke and Parkinson's disease as such play a critical role in wellness and health maintenance. INTRODUCTIONThe consumption of some drugs and chemical substances at various doses could cause malformations in certain developing body organs especially when used during critical periods of development. Such malformations could reflect in the gross and microscopic appearances of affected organs in the mature organisms (Moore & Persaud, 1998). The critical stages of development at which such malformations occur in mammals correspond to the pre-natal and early postnatal lives. In the former circumstance, these substances when consumed by the mother, affect the embryos or foetus only if they cross the blood placental barrier. In the latter circumstance, the substances need to have been administered directly to the neonates or suckled in the breast milk in early post-natal life for them to affect development (Moore & Persaud).The cerebellum is a highly organized structure in which the Purkinje cells (Pc) are the sole output of the cerebellar cortex (Altman, 1969(Altman, , 1972a(Altman, , 1972b(Altman, , 1972c, and it is one of the first structure of the brain to differentiate, however, it achieves its mature configuration many months after birth (Wang & Zoghbi, 2001;Bouet et al., 2005). For this reason, the cerebellum is especially vulnerable to developmental irregularities on exposure to oxidants which generate free radicals resulting in oxidative stress (Wang & Zoghbi;Kern & Jones, 2006). Oxidative stress occurs due to an imbalance in pro-oxidant and antioxidant levels. Scientific evidence sugg...

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Section: Introductionmentioning

confidence: 78%

The Role of Antioxidants in Cerebellar Development: A Review of Literature

Imosemi¹

2013

Int. J. Morphol.

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“…They help in guiding migrating immature neurones; extending through the intermediate zone to the pial region, they form the scaffold for Purkinje and other cells moving from the ventricular zone to their proper positions during embryogenesis [ 37 ]. Disorganization of the Bergmann glial cells, therefore, disrupted the migration of the young neurones [ 38 ], as has been observed in the delayed migration of the external granular cells [ 39 – 41 ]. It has been suggested that Bergmann glial fibres may be responsible for directing the geometrical organization of the cerebellar constituents [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…The thickness of EGL increases for approximately 10 days, then reduces, with the molecular layer replacing it. At postnatal day 21, it is expected for the EGL to have virtually disappeared, with molecular layer extending from the Purkinje cell layer to the pial surface [ 39 , 58 , 59 ]. This reduced radial migration of external granular cells through the molecular layer is a component of impaired cerebellar development [ 60 , 61 ] resulting in hypercellular molecular layer [ 59 ], and this could cause abnormalities of movement and balancing in kola nut-treated rats.…”

Section: Discussionmentioning

confidence: 99%

Kola nut from Cola nitida vent. Schott administered to pregnant rats induces histological alterations in pups’ cerebellum

et al. 2021

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Kola nut (from Cola nitida) is popular in Nigeria and West Africa and is commonly consumed by pregnant women during the first trimester to alleviate morning sickness and dizziness. There is, however, a dearth of information on its effects on the developing brain. This study, therefore, investigated the potential effects of kola nut on the structure of the developing neonatal and juvenile cerebellum in the rat. Pregnant Wistar rats were administered water (as control) or crude (aqueous) kola nut extract at 400, 600, and 800 mg/kg body weight orally, from pregnancy to day 21 after birth. On postnatal days 1, 7, 14, 21 and 28, the pups were weighed, anaesthetised, sacrificed and perfused with neutral buffered formalin. Their brains were dissected out, weighed and the cerebellum preserved in 10% buffered formalin. Paraffin sections of the cerebellum were stained with haematoxylin and eosin for cerebellar cytoarchitecture, cresyl violet stain for Purkinje cell count, Glial Fibrillary Acidic Protein (GFAP) immunohistochemistry (IHC) for estimation of gliosis, and B-cell lymphoma 2 (Bcl-2) IHC for apoptosis induction. The kola nut-treated rats exhibited initial reduction in body and brain weights, persistent external granular layer, increased molecular layer thickness, and loss of Bergmann glia. Their Purkinje cells showed reduction in density, loss of dendrites and multiple layering, and their white matter showed neurodegeneration (spongiosis) and GFAP and Bcl-2 over-expression, with evidence of reactive astrogliosis. This study, therefore, demonstrates that kola nut, administered repeatedly at certain doses to pregnant dams, could disrupt normal postnatal cerebellar development in their pups. The findings suggest potential deleterious effects of excessive kola nut consumption on human brain and thus warrant further studies to understand the wider implications for human brain development.

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“…Ding et al (2013) reported a decreased thickness of the cerebellar EGL on postnatal days 10 and 13 rats treated with arsenic. The thicker EGL observed in the arsenic-treated pups on day 14 may be due to delayed differentiation of the EGL because the EGL is a highly metabolic layer which disappears in humans at approximately two years of age and in mouse, at about days 20 (Hatten and Heintz, 1995;Altman and Bayer, 1985;Imosemi and Osinubi, 2011;Butts et al, 2014). The external granular layer (EGL) consists of highly metabolic cells whose differentiations result in the synthesis of the outer stellate, basket, Golgi type II and granule cells of the cerebellar cortex.…”

Section: Discussionmentioning

confidence: 99%

“…The nervous system, in which the cerebellum is an important part of, is one of the earliest systems to develop embryologically but completes its developmental process postnatally (Hill et al, 2018), and as a result, it is highly prone to any form of injury in prenatal and postnatal life. The cerebellum lies in the posterior cranial fossa of the cranial cavity and functions in the control of smooth and skilful movements, balance, and higher cognitive and emotional functions (Hall et al, 1995;Imosemi and Osinubi, 2011;Hashimoto and Hibi, 2012;Buckner, 2013;Balaei et al, 2017). The cerebellum is highly susceptible to oxidative stress during prenatal and perinatal periods (Lopez, et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Aquoeus Extracts of Daucus Carota (Linn) Protected the Postnatal Developing Cerebellum of Wistar Rats Against Arsenic-Induced Oxidative Stress

Imosemi¹

2021

NJPS

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The neuroprotective effects of the aqueous extract of Daucus carota (Dc) tuber against arsenic-induced oxidative damage on the developing cerebellum of Wistar rats were studied. Twenty-five pregnant rats (110-200g) were divided into five groups (n=5) – control received distilled water; Arsenic (As); Dc (200mg/kg); Dc (200mg/kg) +As; Vitamin C (Vc) (100mg/kg) +As. The pregnant rats in all the groups were treated orally from the first day of pregnancy to postnatal day 21. The Dc extract and Vc were administered one hour before the administration of As. Body weight of the pups on days 1, 7, 14, 21 and 28 were recorded, while neurobehavioural (forelimb grip strength and negative geotaxis) tests were done on day 21 pups. The rats were sacrificed and cerebellar tissues were collected for oxidative stress, histological (H and E), and immunohistochemical studies. Decreased forelimb grip strength, increased lipid peroxidation and decreased glutathione, glutathione peroxidase, catalase and superoxide dismutase was observed in the As group compared with the control and other treated groups. Histologically, the cerebellar cortex of the As pups showed persistent external granular layer (EGL) on postnatal day 21, reduced thickness of the molecular layer (ML) on postnatal day 28, pyknotic and depleted Purkinje cells compared with the control and other treated rats. Immunohistochemical evaluations of the cerebellar cortex showed astroliosis in the As-treated group on day 21 pups compared with the control and other treated groups. Aqueous extracts of Daucus carota and Vitamin C reversed the toxicity caused by arsenic. From the results of the study, arsenic-induced oxidative stress with morphological alterations in the perinatal developing rat cerebellum. Extracts of Daucus carota exhibited antioxidant activity as such may be a potential neuroprotective agent.

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Phenytoin-induced Toxicity in the Postnatal Developing Cerebellum of Wistar Rats, Effect of Calotropis procera on Histomorphometric Parameters

Cited by 8 publications

References 26 publications

The Role of Antioxidants in Cerebellar Development: A Review of Literature

The Role of Antioxidants in Cerebellar Development: A Review of Literature

Kola nut from Cola nitida vent. Schott administered to pregnant rats induces histological alterations in pups’ cerebellum

Aquoeus Extracts of Daucus Carota (Linn) Protected the Postnatal Developing Cerebellum of Wistar Rats Against Arsenic-Induced Oxidative Stress

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