Calcium Supplementation Ameliorates Cerebellar Oxidative Stress in Lactational Aluminum-induced Neurotoxicity in Rats.

Introduction: The neurotoxic effects of aluminum exposure during the critical period of neurodevelopment have been well documented. This study investigated the known protective effects of calcium supplementation on the cerebellum of juvenile Wistar rats following aluminum-induced neurotoxicity during lactation. Methods: Four groups of juvenile rats were exposed via lactation to distilled water (control group), aluminum (40 mg/kg/d), calcium supplement (50 mg/kg/d), and a combination of both aluminum and calcium from postnatal day 4 to day 28. The cerebella of the animals were excised to access the levels of antioxidant enzymes (superoxide dismutase [SOD], glutathione peroxidase [GPx]), lipid peroxidation (malondialdehyde), histomorphological alterations (hematoxylin and eosin staining), Nissl profile (cresyl fast violet staining), and glial activation (glial fibrillary acidic protein immunohistochemistry). Results: Lactational aluminum significantly decreased the activities of superoxide dismutase and glutathione peroxidase while exacerbating lipid peroxidation and reactive astrocyte in cerebellar lysates. Lactational calcium supplementation normalized the activities of SOD and GPx, thereby preventing excessive lipid peroxidation and glial activation. Despite no apparent changes in the general histology of the cerebellum, aluminum-induced chromatolysis changes in the Purkinje cell layer, which was counteracted by the antioxidant propensities of calcium supplementation. Conclusion: These findings support that calcium supplementation significantly protects the cerebellum against aluminum-induced oxidative stress, chromatolysis, and neuroinflammation.

Lead acetate- induced neurodegenerative changes in the dorsolateral prefrontal cortex of mice: the role of Vitexin.

This study was aimed at investigating the neuroprotective effect of Vitexin against lead (Pb) induced neurodegenerative changes in the dorsolateral prefrontal cortex (DLPFC) and working memory in mice. Thirty-two adolescent male albino mice were divided into four groups (n=8). Control group received 0.2 mL of normal saline; Pb group received 100 mg/kg of Pb acetate for 14 days, Vitexin group received 1mg/kg of Vitexin for 14 days, and Pb+Vitexin group received 100 mg/kg of Pb acetate and 1 mgkg of Vitexin for 14 days. Barnes maze test and novel object recognition test were done to ascertain working memory. Histoarchitectural assessment of DLPFC was done with haematoxylin and eosin (H&E), cresyl fast violet and congo red stains. Furthermore, cell count and other morphometric measurements were done. There was significant decline in working memory in the Pb group, but a combination of Pb+Vitexin improved the working memory. Vitexin significantly reduced neuronal death and chromatolysis caused by Pb. Amyloid aggregation was not observed in any of the groups. This study has shown that concurrent administration of Vitexin and Pb will significantly reduce neurodegeneration and improve working memory. However, Pb treatment or Pb+Vitexin treatment does not have any effect on intercellular distance, neuronal length and the cross-sectional area of neurons in layer III of DLPFC.

Kolaviron protects against cognitive deficits and cortico-hippocampal perturbations associated with maternal deprivation in rats.

Prolonged separation of pups from their mother in early postnatal period can interfere with normal growth and development, resulting in different behavioral changes similar to features of schizophrenia in man. This study explored the cytoprotective action of kolaviron, a biflavonoid, on the prefrontal cortex and hippocampus of maternally deprived Wistar rats. Eight months old female rats were time-mated, and after delivery their pups were randomly assigned into four groups; group A received 0.5 ml of normal saline, group B received kolaviron orally (200 mg/kg/bw) on postnatal days (PND) 21-35, group C were maternally deprived on PND 9 for 24 hours, while group D were also maternally deprived on PND 9 for 24 hours, and then received kolaviron orally (200 mg/kg/bw) on PND 21-35. Behavioral studies (open field test, Morris water test, and Y-maze test) were conducted after the experiment prior to sacrifice. Some of the rats were anesthetized with ketamine and perfusion-fixed with 0.1 M phosphate buffered saline and 4% paraformaldehyde, while others were sacrificed by cervical dislocation for enzyme studies. The hippocampus and prefrontal cortex were excised from the brain and processed for tissue histology, histochemistry, and enzymatic analysis. Results revealed behavioral deficits, oxidative stress, degenerative changes, and astrocytosis in the prefrontal cortex and hippocampus of maternally deprived rats, but intervention with kolaviron caused significant improvement in neurobehavior, morphology, and neurochemistry in these brain areas. We concluded that kolaviron could protect the brain against neurological consequences of nutritional and environmental insults arising from maternal separation in early postnatal period.

The Protective Effect of Kolaviron on Molecular, Cellular, and Behavioral Characterization of Cerebellum in the Rat Model of Demyelinating Diseases.

INTRODUCTION: This study aimed at assessing the protective mechanisms of Kolaviron (KV) on the cerebellum in a rat model of demyelination. METHODS: Twenty-eight male Wistar rats were used in the present study. They were randomly divided into 4 groups of 7 rats. Group A (control) received corn oil (0.5 mL/kg/d); group B received 0.2% Cuprizone (CPZ); group C was treated with 200 mg/kg/d of KV, and group D received 0.2% CPZ and 200 mg/kg/d KV for 6 weeks. CPZ powder was mixed with the regular diet while KV was dissolved in corn oil and administered orally. A behavioral test was conducted at the termination of the experiment. Thereafter, the animals were sacrificed and their brains were removed with the excision of the cerebellum. A part of the cerebelli underwent tissue processing with a series of 5 µm thick sections cut from paraffin blocks for histological and immunohistochemical assessment. Besides, the remaining cerebellar tissues were homogenized for the spectrophotometric assays of Oxidative Stress (OS) parameters. RESULTS: The current research findings revealed minimal weight gain following CPZ treatment, but significant weight increase in KV-treated rats. CPZ treatment was associated with a reduction in the number of the line crossed, rearing frequency, rearing duration, center square entry, and center square duration; however, it increased the freezing time, i.e. significantly reversed in the KV-treated animals. Oxidative markers, such as Superoxide Dismutase (SOD) and GPx were reduced in CPZ-treated rats with elevated MDA levels. However, these data were significantly reversed by the co-administration of CPZ and KV. At the tissue level, the cerebellar cortex was characterized by poorly defined layers, cryptic granules, as well as chromatolysis and pyknotic Purkinje cells with the evidence of hypertrophic astrogliosis. CONCLUSION: CPZ treatment significantly depressed locomotor and exploratory activities. Furthermore, it increased OS and cerebellar toxicity. However, KV intervention significantly enhanced behavioral functions and ameliorated CPZ-induced cerebellar degeneration. Moreover, it considerably regulated OS markers in the cerebellum of the rat model of demyelinating diseases.

Ameliorative effects of Moringa on cuprizone-induced memory decline in rat model of multiple sclerosis.

Cuprizone is a neurotoxin with copper-chelating ability used in animal model of multiple sclerosis in which oxidative stress has been documented as one of the cascade in the pathogenesis. Moringa oleifera is a phytomedicinal plant with antioxidant and neuroprotective properties. This study aimed at evaluating the ameliorative capability of M. oleifera in cuprizone-induced behavioral and histopathological alterations in the prefrontal cortex and hippocampus of Wistar rats. Four groups of rats were treated with normal saline, cuprizone, M. oleifera and a combination of M. oleifera and cuprizone, for five weeks. The rats were subjected to Morris water maze and Y-maze to assess long and short-term memory respectively. The animals were sacrificed, and brain tissues were removed for histochemical and enzyme lysate immunosorbent assay for catalase, superoxide dismutase, and nitric oxide. Cuprizone significantly induced oxidative and nitrosative stress coupled with memory decline and cortico-hippocampal neuronal deficits; however, administration of M. oleifera significantly reversed the neuropathological deficits induced by cuprizone.

Kolaviron protects the brain in cuprizone-induced model of experimental multiple sclerosis via enhancement of intrinsic antioxidant mechanisms: Possible therapeutic applications?

Multiple sclerosis is a demyelinating condition of the central nervous system which commonly affects young adults. Kolaviron, a biflavonoid isolate of Garcinia kola, has been used in experimental studies which explored its anti-oxidative, anti-inflammatory and anti-genotoxic properties. This work was aimed at unraveling the possible ameliorative effect of kolaviron on cuprizone-induced demyelination in the prefrontal cortices of Wistar rats. A total of 28 adult male Wistar rats were divided into four groups A-D. Group A received corn oil (Control), group B received 0.2% Cuprizone, group C received kolaviron (200 mg/kg bw), while group D rats were treated concomitantly with both kolaviron and cuprizone. All groups were treated for 42 days, after which behavioral, histological, immunohistochemical and biochemical analyses were carried out on the prefrontal cortices. Cuprizone significantly down-regulated the level of superoxide dismutase, exacerbated lipid peroxidation and, reduced spatial memory. Cuprizone also induced peripheral and central chromatolysis alongside with atrophied astrocytes in the prefrontal cortex. These alterations were significantly prevented in kolaviron-treated rats, as kolaviron sustained the integrity of neuronal and non-neuronal cells. The activity of kolaviron observed in this study was due to its intrinsic antioxidant properties, which enabled it to combat oxidative damage induced by cuprizone, thereby making kolaviron a potential tool in neurodegeneration therapy of demyelination origin.

Moringa oleifera phytochemicals protect the brain against experimental nicotine-induced neurobehavioral disturbances and cerebellar degeneration.

Nicotine is a neuro-stimulant that has been implicated in the pathophysiology of many brain diseases. The need to prevent or alleviate the resulting dysfunction is therefore paramount, which has also given way to the use of medicinal plants in the management of brain conditions. This study was designed to determine the histomorphological and neurobehavioural changes in the cerebellum of Wistar rats following nicotine insult and how such injuries respond to Moringa intervention. Twenty-four adult male Wistar rats were divided into 4 groups. Group A and B were orally treated with normal saline and Moringa oleifera respectively for twenty-eight days; Group C was treated with nicotine while group D was treated orally with Moringa oleifera and intraperitoneally with nicotine for twenty-eight days. Animals were subjected to the open field test on the last day of treatment. 24 h after last day treatment, the animals were anesthetized and perfusion fixation was carried out. The cerebellum was excised and post-fixed in 4% paraformaldehyde and thereafter put through routine histological procedures. Results revealed cytoarchitectural distortion and extreme chromatolysis in neuronal cells of the cerebellar cortical layers in the nicotine-treated group. The Purkinje cells of the cerebellum of animals in this group were degenerated. There were also reduced locomotor activities in the group. Moringa was able to prevent the chromatolysis, distortion of the cerebellar cortical cells and neurobehavioural deficit. Our result suggests that Moringa oleifera could prevent nicotine-induced cerebellar injury in Wistar rats, with the possibility of ameliorating the clinical features presented in associated cerebellar pathology.

Prenatal Exposure to Gestational Nicotine before Neurulation is Detrimental to Neurodevelopment of Wistar Rats' Offspring.

BACKGROUND AND AIM: This study aimed to determine the effect of gestational nicotine exposure before neurodevelopment on the morphology and histology of the prefrontal cortex (PFC) in rats. METHODOLOGY: Adult female Wistar rats were time-mated and grouped into three categories: (a) control-given 0.1 mL of normal saline, (b) low-dose nicotine-given 6.88 mg/ kg/d/0.05 mL, and (c) high-dose nicotine-given 13.76 mg/kg/d/0.1 mL in two divided doses. Treatment was given intraperitoneally from gestational days 2 to 6. On postnatal day 15 (P15), the pups were separated from their mothers, anaesthetised and sacrificed, followed by intracardial perfusion with 4% paraformaldehyde. PFC was excised from the brain and processed for tissue histology, histochemistry, and morphology of brain cells. RESULTS: Gestational nicotine exposure during the first week of gestation in rats significantly reduced birth weights in nicotine-treated groups compared with control; it, however, accelerated body weights, altered neuronal morphology, and elevated astrocytic count significantly, while oligodendroglial count was slightly increased in the PFC of juvenile rats examined at P15. CONCLUSION: These alterations revealed that gestational nicotine exposure before the commencement of the cellular processes involved in brain development negatively affects neurodevelopment, and this could result in neurological dysfunctions in later life.

Kolaviron Protects the Prefrontal Cortex and Hippocampus against Histomorphological and Neurobehavioural Changes in Cuprizone Model of Multiple Sclerosis.

BACKGROUND: This study explored the efficacy of kolaviron-a biflavonoid complex isolated from the seeds of Garcinia kola-in protecting against cuprizone (CPZ)-induced demyelination in both the prefrontal cortex and the hippocampus of Wistar rats. METHODOLOGY: Thirty rats were treated to receive 0.5 mL phosphate-buffered saline (group A, control), 0.5 mL corn oil (group B), 0.2% CPZ (group C), for 6 weeks, 0.2% CPZ for 3 weeks and then 200 mg/kg of Kv for 3 weeks (group D), or 200 mg/kg of Kv for 3 weeks followed by 0.2% CPZ for 3 weeks (group E). Rats were assessed for exploratory functions and anxiety-like behaviour before being euthanised and perfused transcardially with 4% paraformaldehyde. Prefrontal and hippocampal thin sections were stained in hematoxylin and eosin and cresyl fast violet stains. RESULTS: CPZ-induced demyelination resulted in behavioural impairment as seen by reduced exploratory activities, rearing behaviour, stretch attend posture, center square entry, and anxiogenic characteristics. Degenerative changes including pyknosis, karyorrhexis, neuronal hypertrophy, and reduced Nissl integrity were also seen. Animals treated with Kv showed significant improvement in behavioural outcomes and a comparatively normal cytoarchitectural profile. CONCLUSION: Kv provides protective roles against CPZ-induced neurotoxicity through prevention of ribosomal protein degradation.

Moringa oleifera impairs the morphology and functions of the kidney in adult Wistar rats / Moringa oleifera altera la morfología y funciones del riñón en ratas Wistar adultas

We tested the hypothesis that Moringa oleifera impairs the morphology and functions of the kidney in rats. Twenty-four adult male Wistar rats were employed in the study. Rats of Control Group I received physiological saline while rats of Groups II ­ IV received 250, 500 and 750 mg/kg bodyweight of methanolic extract of Moringa oleifera respectively for twenty one days. No behavioral anomalies were observed in rats of Groups I ­ IV. Rats of Control Group I gained statistically significant increased bodyweight while rats of Groups II ­ IV experienced non-significant decreased bodyweight during experimental procedure. (P0.05). No statistical significant differences (P0.05) were observed in the analyses of the relative weights of kidneys of rats of Groups I ­ IV. Histological examinations showed normal cyto-architecture of the kidneys of rats of Group I while the Capsular spaces of the kidneys of rats of Groups II ­ IV appeared wider than those of Group I. Statistical analyses showed significant higher levels (P0.05) of Alanine and Aspartate Transaminases, and serum urea in rats of Groups II ­ IV in a non- dose-dependent manner when compared to rats of Group I. Our findings are consistent with the stated hypothesis.

Se puso a prueba la hipótesis que Moringa oleifera altera la morfología y función del riñón en ratas. Fueron utilizadas 24 ratas Wistar macho adultas. El grupo control recibió suero fisiológico mientras que los Grupos II a IV recibieron 250, 500 y 750 mg/kg peso corporal del extracto metanólico de Moringa oleifera respectivamente, durante 21 días. No se observaron anomalías en el comportamiento en ratas de los Grupos I - IV. En las ratas del grupo de control se registró un aumento de peso corporal estadísticamente significativo, mientras que las ratas de los grupos II - IV experimentaron una disminución no significativa de peso corporal durante el procedimiento experimental (P0,05). No se observaron diferencias estadísticamente significativas (P0,05) en el análisis de los pesos relativos en riñones de las ratas de los grupos I - IV. Los exámenes histológicos mostraron citoarquitectura normal de los riñones de las ratas del grupo I, mientras que en ratas de los grupos II ­ IV los espacios capsulares de los riñones aparecían más amplios que los del Grupo I. Los análisis estadísticos mostraron niveles superiores significativos ( P 0,05 ) de la alanina y aspartato aminotransferasa, y de urea en suero en ratas de los Grupos II - IV no dependiente de la dosis, en comparación con las ratas del Grupo I. Estos resultados coinciden con la hipótesis planteada.

Liver enzymes derangement and the influence of diet in animals given oral albendazole.

BACKGROUND: Albendazole is used as an anthelmintic in the treatment of some parasitic infections. This study determined how the effects of albendazole on liver enzymes are influenced by diet. MATERIALS AND METHOD: Thirty adult male Wistar rats of mean weight 304.12 ± 11.34 g were randomly grouped into five: Group A: Control, was given rat pellets and water only; Group B received 15 mg/kg/d of albendazole while fasting; Group C received 15 mg/kg/d of albendazole with fatty meal; Group D received 15 mg/kg/d of albendazole with normal diet (rat pellets); and, Group E received 30 mg/kg/d of albendazole with normal diet (rat pellets); they were given orally for 3 consecutive days. The animals were sacrificed thereafter and blood samples obtained for quantitative study of the serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). RESULTS: Significant elevation in the serum levels of the transaminases especially in animals which were on their normal diet (rat pellets), while ALP was either reduced or increased based on dietary factors. CONCLUSIONS: Oral administration of albendazole before meal or with a fatty diet could help limit severe elevation of liver enzymes associated with its use, while still ensuring optimal efficacy.

Effects of combined leaf extract of Vernonia amygdalina and Azadirachta indica on hepatic morphology and hepatotoxicity markers in streptozotocin-induced diabetic rats.

OBJECTIVES: In this work, we studied liver morphology, markers of hepatic oxidative stress and some liver enzymes in diabetic rats treated with the combined leaf extract (CLE) of Vernonia amygdalina (bitter leaf) and Azadirachta indica (neem). METHODS: Diabetes was induced in fasted male Wistar rats with intraperitoneal injection of streptozotocin (STZ). Oral CLE (500 mg/kg body weight) and metformin (150 mg/kg body weight) were administered to different groups of diabetic rats for eight weeks. Blood glucose and change in body weight were estimated weekly. All animals were sacrificed under anaesthesia after eight weeks. Hepatic sections were stained with periodic acid-Schiff. Liver samples were homogenized and assayed for contents of malondialdehyde (MDA) and glutathione peroxidase (GPx), while the plasma was assayed for contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). RESULTS: Metformin and CLE treatment produced normoglycaemia in the diabetic rats in the course of the treatment period. Significant increases in body weight were observed in the treatment groups compared with the diabetic control rats (P<0.05). In the control and treatment groups, light microscopic study showed intact hepatic histology. Plasma ALT and AST were not significantly different from the control values in the CLE-treated rats. In addition, from week four onwards, blood glucose concentrations in the CLE-treated rats were not different from the normal control (P>0.05). Besides, hepatic MDA (P<0.05) significantly decreased in the CLE-treated rats compared with the normal control. CONCLUSION: These findings suggest that CLE ameliorates hyperglycemia and hepatic oxidative stress when administered to diabetic rats as a chronic regimen, and there was no morphologic or biochemical evidence of liver damage at the dose tested.

Effects of combined leaf extract of Vernonia amygdalina and Azadirachta indica on hepatic morphology and hepatotoxicity markers in streptozotocin-induced diabetic rats / 中西医结合学报

In this work, we studied liver morphology, markers of hepatic oxidative stress and some liver enzymes in diabetic rats treated with the combined leaf extract (CLE) of Vernonia amygdalina (bitter leaf) and Azadirachta indica (neem).