Vanadium administration ameliorates cortical structural and functional changes in juvenile hydrocephalic mice.

Vanadium is a prevalent neurotoxic transition metal with therapeutic potentials in some neurological conditions. Hydrocephalus poses a major clinical burden in neurological practice in Africa. Its primary treatment (shunting) has complications, including infection and blockage; alternative drug-based therapies are therefore necessary. This study investigates the function and cytoarchitecture of motor and cerebellar cortices in juvenile hydrocephalic mice following treatment with varying doses of vanadium. Fifty juvenile mice were allocated into five groups (n = 10 each): controls, hydrocephalus-only, low- (0.15 mg/kg), moderate- (0.3 mg/kg), and high- (3.0 mg/kg) dose vanadium groups. Hydrocephalus was induced by the intracisternal injection of kaolin and sodium metavanadate administered by intraperitoneal injection 72hourly for 28 days. Neurobehavioral tests: open field, hanging wire, and pole tests, were carried out to assess locomotion, muscular strength, and motor coordination, respectively. The cerebral motor and the cerebellar cortices were processed for cresyl violet staining and immunohistochemistry for neurons (NeuN) and astrocytes (glial fibrillary acidic protein). Hydrocephalic mice exhibited body weight loss and behavioral deficits. Horizontal and vertical movements and latency to fall from hanging wire were significantly reduced, while latency to turn and descend the pole were prolonged in hydrocephalic mice, suggesting impaired motor ability; this was improved in vanadium-treated mice. Increased neuronal count, pyknotic cells, neurodegeneration and reactive astrogliosis were observed in the hydrocephalic mice. These were mostly mitigated in the vanadium-treated mice, except in the high-dose group where astrogliosis persisted. These results demonstrate a neuroprotective potential of vanadium administration in hydrocephalus. The molecular basis of these effects needs further exploration.

Leaf extract of Anacardium occidentale ameliorates biomarkers of neuroinflammation, memory loss, and neurobehavioral deficit in N(ω)-nitro-L-arginine methyl ester (L-NAME) treated rats.

PURPOSE: Anacardium occidentale commonly known as Cashew is a plant that is widely used in African traditional medicine. It is endowed with phytochemical constituents that are responsible for its medicinal properties. METHODS: Twenty-five male Wistar rats were grouped as follows: Control (Group A), Group B (L-NAME 40 mg/kg), Group C (100 mg/kg Anacardium occidentale extract plus 40 mg/kg L-NAME), Group D (200 mg/kg extract plus 40 mg/kg L-NAME) and Group E (10 mg/kg of Lisinopril plus 40 mg/kg L-NAME). The animals were treated with oral administration of either the extracts or Lisnopril daily for 4 weeks. Neuro-behavioural tests such as the Morris Water Maze and Hanging Wire Grip tests were carried out to evaluate memory/spatial learning and muscular strength, respectively. Makers of oxidative stress, antioxidant enzymes and immunohistochemical staining of Glial Fibrillary Acidic Protein and Ionised Calcium Binding Adaptor molecule 1 were assessed. RESULTS: L-NAME administration caused significant increases in biomarkers of oxidative stress, decreased antioxidant status, acetylcholinesterase activity, altered neuro-behavioural changes, astrocytosis, and microgliosis. However, Anacardium occidentale reversed exaggerated oxidative stress biomarkers and improved neuro-behavioural changes. CONCLUSIONS: Combining all, Anacardium occidentale enhanced brain antioxidant defence status, improved memory and muscular strength, thus, suggesting the neuroprotective properties of Anacardium occidentale.

Ameliorative effects of the aqueous extract of Khaya anthotheca (Welw.) C.DC (Meliaceae) in vanadium induced anxiety, memory loss and pathologies in the brain and ovary of mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanical enquiries have revealed that Khaya anthotheca (Welw.) C.DC (Meliaceae) has anxiolytic properties and is used to alleviate vaginal dryness in postmenopausal women in Cameroon. The aim of this study was to evaluate the ameliorative effects of the aqueous extract of K. anthotheca in vanadium induced anxiety, memory loss and pathologies in the brain and ovary of mice. MATERIAL AND METHODS: Forty neonatal female mice were used in this study. All animals received vanadium (3 mg/kg BW/72 h, by lactation and i.p.) for 20 weeks except the Control group. At 16 weeks old, mice were divided into 5 groups (n = 8): Control group received distilled water; V-group received vanadium (V) (3 mg/kg BW every 72 h i.p.), V + Vit E group received vitamin E (500 mg/kg BW/72 h) and vanadium (V) (3 mg/kg BW/72 h i.p, simultaneously). V + KA 125 and V + KA 250 groups received K. anthotheca extract at the doses of 125 and 250 mg/kg BW/day respectively and vanadium (V) (3 mg/kg BW/72 h i.p, simultaneously).The treatment was done per os at 10 mL/kg of volume of administration for 4 weeks. To evalute anxiolytic effects and spatial working memory improved by the extract in mice, the elevated open space test and Y maze test were used respectively. After sacrifice, brains were harvested and pathologies were assessed using cresyl violet stainning and immunohistochemistry (GFAP, Iba-1 and MBP), while pathologies in the ovaries were assessed using immunohistochemistry (Collagen type 1) and H&E stainning. RESULTS: Results in the three sessions of elevated open space test showed that vanadium exposure resulted in a significant (p < 0.05; p < 0.01) increase of the latency of first entry in the slopes and a significant (p < 0.05; p < 0.01; p < 0.001) decrease of the time spent and number of entries in the slopes however, Khaya anthotheca treatment induced a significant (p < 0.05; p < 0.01) decrease of the latency of first entry in the slopes and a significant (p < 0.05; p < 0.01) increase of the time spent and number of entries in the slopes. In the Y maze test, vanadium exposure resulted in a significant decrease (p < 0.01) in the percentage of correct alternation, K. anthotheca extract at the dose of 250 mg/kg BW however induced a significant (p < 0.05) increase of this percentage of correct spontaneous alternation. In the brain, degeneration induced by vanadium exposure was marked by an increase of GFAP-immunoreactive cells, microgliosis and demyelination. The treatment with Khaya anthotheca extract at the dose of 250 mg/kg BW resulted in the preservation of cellular integrity in the same anatomical regions with reduced astroglial and microglial activation and prevented demyelination. In addition, vanadium exposure decreased Collagen type 1 expression in the ovaries and induced a deterioration of tertiary follicle. Khaya anthotheca treatment at the dose of 250 mg/kg BW induced an increase of expression of Collagen type 1 and alleviated deterioration of the microarchitecture of tertiary follicle induced by vanadium. CONCLUSION: These effects induced by K. anthotheca extract could justify the traditional use of this plant in Cameroonian traditional medicine to manage anxiety. Therefore, to minimise vanadium induced toxicity, the plant should be given more emphasis as a candidate in developing a modern phytodrug.

Kolaviron and Garcinia kola attenuate doxorubicin-induced cardiotoxicity in Wistar rats.

Background The Garcinia kola seeds have been reported for its antibacterial, antioxidant, antidiabetic and also for its chemoprevention property. The use of doxorubicin as an anticancer drug has been accompanied with avalanche of side effects including cardiotoxicity. The aim of this study was to investigate the cardioprotective effect of Kolaviron and Garcinia kola and their mechanisms of action. Methods Sixty male rats (Wistar strain) were used in this study. They were divided into 6 groups (A-F) each containing 10 animals. Group A was the control. Rats in Groups B, C, D, E and F were treated with doxorubicin at the dosage of 15 mg/kg body weight i.p. Prior to this treatment, rats in groups C, D, E and F were pre-treated orally with Kolaviron at the dosage of 100 mg/kg and 200 mg/kg, and Garcinia kola 100 mg/kg and 200 mg/kg for 7 days, respectively. Results The results show that doxorubicin caused a significant increase in heart rate and prolonged QT, reduced antioxidant status, increased oxidative stress, inflammation and markers of cardiac damage which were reversed by pre-treatment with Kolaviron and Garcinia kola. Conclusions Overall, pre-treatment with Kolaviron or Garcinia kola caused reversal of cardiac damage, ECG alteration and oxidative stress by increasing the activity of antioxidant enzymes and reducing the markers of inflammation on doxorubicin-induced cardiotoxicity.