Sodium metavanadate induced cognitive decline, behavioral impairments, oxidative stress and down regulation of myelin basic protein in mice hippocampus: Ameliorative roles of β‐spinasterol, and stigmasterol

Abstract

IntroductionExposures to toxic levels of vanadium and soluble vanadium compounds cause behavioral impairments and neurodegeneration via free radical production. Consequently, natural antioxidant sources have been explored for effective and cheap remedy following toxicity. Grewia carpinifolia has been shown to improve behavioral impairments in vanadium‐induced neurotoxicity, however, the active compounds implicated remains unknown. Therefore, this study was conducted to investigate ameliorative effects of bioactive compounds from G. carpinifolia on memory and behavioral impairments in vanadium‐induced neurotoxicity.MethodsSixty BALB/c mice were equally divided into five groups (A–E). A (control); administered distilled water, B (standard); administered α‐tocopherol (500 mg/kg) every 72 hr orally with daily dose of sodium metavanadate (3 mg/kg) intraperitoneally, test groups C, and D; received single oral dose of 100 μg β‐spinasterol or stigmasterol (bioactive compounds from G. carpinifolia), respectively, along with sodium metavanadate and the model group E, received sodium metavanadate only for seven consecutive days. Memory, locomotion and muscular strength were accessed using Morris water maze, Open field and hanging wire tests. In vivo antioxidant and neuroprotective activities were evaluated by measuring catalase, superoxide dismutase, MDA, H2O2, and myelin basic protein (MBP) expression in the hippocampus.ResultsIn Morris water maze, stigmasterol significantly (p ≤ 0.05) decreased escape latency and increased swimming time in target quadrant (28.01 ± 0.02; 98.24 ± 17.38 s), respectively, better than α‐tocopherol (52.43 ± 13.25; 80.32 ± 15.21) and β‐spinasterol (42.09 ± 14.27; 70.91 ± 19.24) in sodium metavanadate‐induced memory loss (112.31 ± 9.35; 42.35 ± 11.05). β‐Spinasterol and stigmasterol significantly increased exploration and latency in open field and hanging wire tests respectively. Stigmasterol also increased activities of antioxidant enzymes, decreased oxidative stress markers and lipid peroxidation in mice hippocampal homogenates, and increased MBP expression.ConclusionsThe findings of this study indicate a potential for stigmasterol, a bioactive compound from G. carpinifolia in improving cognitive decline, motor coordination, and ameliorating oxidative stress in vanadium‐induced neurotoxicity.

Protective Effects of Dietary Antioxidants against Vanadium-Induced Toxicity: A Review

“…Although limited in number, there are studies evaluating the effects of phytosterols on vanadium-induced toxicity, as described below. The oral administration of stigmasterol and β-sitosterol significantly attenuated neurobehavioral impairments such as deficits in exploration, learning and 7 Oxidative Medicine and Cellular Longevity memory disabilities, and decreased motor coordination, which were induced by sodium metavanadate in mice [106,107]. Additionally, in these studies, the two sterols mentioned above exerted an inhibitory effect on hydrogen peroxide generation and lipid peroxidation and improved the activities of superoxide dismutase and catalase in brain tissue of vanadium-exposed mice.…”

“…Additionally, in these studies, the two sterols mentioned above exerted an inhibitory effect on hydrogen peroxide generation and lipid peroxidation and improved the activities of superoxide dismutase and catalase in brain tissue of vanadium-exposed mice. Therefore, the authors proposed that the neuroprotective effects of stigmasterol and β-sitosterol could be associated with reduced levels of oxidative stress [106,107]. The exact mechanism of the antioxidant activity of phytosterols is not well understood.…”

Pharmacological effects of medicinal components of Atractylodes lancea (Thunb.) DC.

“…More precisely, stigmasterol could reduce escape latency and prolong swimming time in Morris water maze. Also, stigmasterol could promote activities of antioxidant enzymes, and inhibit oxidative stress markers as well as lipid peroxidation in mice hippocampal homogenates [ 69 ]. A recent study showed that stigmasterol could protect mice from LPS-induced fever response.…”

Peripheral axonopathy in sciatic nerve of adult Wistar rats following exposure to vanadium

“…13 In addition, vanadium has been shown to have effects on the nervous system, where it has been established to cross the blood-brain barrier, [14][15][16] bioaccumulate in brain tissue 16 and exert (acute and chronic) neuropathologies and behavioural deficits. [17][18][19][20][21][22][23][24] Much like the brain, the peripheral nervous system is characterised by highly peroxidizable fatty acids tissue, low levels of antioxidants and high aerobic metabolism. 25 These features put together, render this system highly susceptible to oxidative stress.…”

“…Some of the vanadium‐induced pathologies reported on various organ systems include: the lungs, liver, spleen, and testes, haematological and biochemical alterations and the kidneys . In addition, vanadium has been shown to have effects on the nervous system, where it has been established to cross the blood‐brain barrier, bioaccumulate in brain tissue and exert (acute and chronic) neuropathologies and behavioural deficits …”