Protective effect of cholecalciferol against cobalt-induced neurotoxicity in rats: ZO-1/iFABP, ChAT/AchE and antioxidant pathways as potential therapeutic targets.

Cobalt (Co) toxicity has been reported to produce central nervous system and gastrointestinal abnormalities. This study assessed the therapeutic effect of cholecalciferol (Cho) supplementation against damages caused by sub-acute (14-day) cobalt chloride (CoCl2) exposure in the brain and intestines. Thirty-five male Wistar rats were divided equally into five groups: Group I (control) received no treatment; Group II received oral CoCl2 (100 mg/kg) only; Groups III, IV, and V received 1000, 3000 and 6000 IU/kg of cholecalciferol, respectively by oral gavage, and concurrently with CoCl2. Cobalt-treated rats showed neuronal vacuolation and presence of pyknotic nuclei in the cerebral cortex and hippocampus, depletion of Purkinje cells in the cerebellum, as well as inflammation and congestion in the intestinal mucosa. Cobalt also increased brain and intestinal hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentrations, while simultaneously reducing glutathione (GSH) content, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities. Further, CoCl2 induced increases in brain acetylcholinesterase (AchE) activity and serum zonulin (ZO-1) levels. Conversely, Cho administration suppressed CoCl2-induced damages in the brain and intestines by reducing lipid peroxidation and increasing the activities of antioxidant enzymes. Remarkably, Cho produced stimulation of brain choline acetyltransferase (ChAT) and suppression of AchE activity, along with dose-dependent reduction in serum levels of ZO-1, intestinal fatty acid-binding protein (iFABP) and nitric oxide. In conclusion, the protective role of cholecalciferol against cobalt-induced toxicity occurred via modulation of cholinergic, intestinal permeability and antioxidant pathways. The results may prove significant in the context of the role of gut-brain connections in neuroprotection.

Amelioration of Aflatoxin B1-induced gastrointestinal injuries by Eucalyptus oil in rats.

Background Eucalyptus oil (EO), derived from Eucalyptus species, possesses vast remedial and healing properties, although its gut health-promoting properties have not been well investigated. In this study, we investigated the chemical composition of a commercial EO formulation and its potential role in protecting against aflatoxin B1 (AfB1)-induced gastrointestinal damage in rats. Methods Male Wistar rats were divided into six groups with eight rats each. Control rats were administered with the vehicle (1% Tween 80) for 14 days, while another group was exposed to two oral doses of AFB1 on days 12 and 14. Two other groups were pre-treated with oral doses of EO (50 and 100 mg/kg b.w.) for 14 consecutive days, along with two oral doses of AfB1 (5 mg/kg b.w.) on days 12 and 14. The remaining two groups were treated with EO alone at the two doses for 14 days. At the end of the experiment, blood samples, stomach and intestinal tissues were collected for measurement of oxidative stress and antioxidant parameters and light microscopic examination. Results Gas chromatography-mass spectrometry analysis revealed Eucalyptol (1, 8-cineole) as the main constituent (67.48%) of the oil. AfB1 administration induced oxidative and inflammatory disturbances, indicated by significantly (p<0.05) increased serum nitric oxide level and myeloperoxidase activity; increased tissue contents of hydrogen peroxide, malondialdehyde and protein carbonyls, accompanied with corresponding histological alterations. AfB1 also induced significant (p<0.05) reductions in glutathione peroxidase and superoxide dismutase (SOD) activities. Treatment with EO produced significant improvements in the biochemical parameters as well as the appearance of the gastric and intestinal mucosa. EO alone, at the two doses tested did not produce any significant changes in the parameters investigated. Conclusion The findings from this study showed that EO demonstrated protective activity against Aflatoxin-induced toxicity in stomach and intestinal tissues and may thus find application in treatment of gastrointestinal disorders.

Neuroprotection by luteolin and gallic acid against cobalt chloride-induced behavioural, morphological and neurochemical alterations in Wistar rats.

Cobalt (Co) intoxication arising from occupational exposures and ion release from metal implants has been associated with neurological alterations such as cognitive decline, incoordination and depression. The present study evaluated the mechanisms of neuro-protection exerted by Luteolin (Lut; 100 mg/kg) and Gallic acid (GA; 120 mg/kg) in Wistar rats exposed to cobalt chloride (CoCl2) at 150 mg/kg for 7 consecutive days. Results indicate that CoCl2 induced neuro-behavioural deficits specifically by decreasing exploratory activities of CoCl2-exposed rats, increased anxiety, as well as significant reduction in hanging latency. Co-treatment with Lut or GA, however, restored these parameters to values near those of normal controls. Moreover, Lut and GA prevented CoCl2-induced increases in hydrogen peroxide (H2O2), malondialdehyde (MDA) and nitric oxide (NO) in the brain, while also restoring the activities of acetylcholinesterase, glutathione S-transferase (GST) and superoxide dismutase (SOD). In addition, Lut and GA produced significant reversal of CoCl2-induced elevation in levels of serum Interleukin 1 beta (IL-1ß) and Tumor necrosis factor (TNFα). Meanwhile, immunohistochemistry revealed increased astrocytic expression of glial fibrillary acidic protein (GFAP), with intense calbindin (CB) D-28k staining and pronounced dendrites in the Purkinje cells. In contrast, the CoCl2 group was characterized by decreased number of neurons expressing CB and dendritic loss. Taken together, mechanisms of luteolin and/or gallic acid protection against Co toxicity involved restoration of Ca2+ homeostasis, acetylcholinesterase and antioxidant enzyme activities, as well as inhibition of lipid peroxidation in the brain.

Alterations in blood pressure, antioxidant status and caspase 8 expression in cobalt chloride-induced cardio-renal dysfunction are reversed by Ocimum gratissimum and gallic acid in Wistar rats.

The protective abilities of the chloroform extract of Ocimum gratissimum (COG) and gallic acid against cobalt chloride (CoCl2) - induced cardiac and renal toxicity were evaluated. Rats were exposed to CoCl2 (350ppm) for 7 days, either alone, or in combination with COG (100 and 200mg/kg) or gallic acid (120mg/kg). CoCl2 given alone, caused significant increases (p<0.05) in oxidative stress parameters (hydrogen peroxide, H2O2 and malondialdehyde, MDA) and increased expression of the apoptotic initiator caspase 8 in the heart and kidneys. There was significant reduction (p<0.05) in reduced glutathione (GSH) in cardiac and renal tissues; reduction in superoxide dismutase (SOD) activity in the kidneys and adaptive increases in Glutathione S-transferase (GST) and catalase (CAT). CoCl2 also produced significant reduction (p<0.05) in systolic (SBP), diastolic (DBP) and mean arterial (MAP) blood pressures. Oral COG and gallic acid treatment significantly reduced (p<0.05) the levels of H2O2 and MDA; with reduced expression of caspase 8 and restoration of GSH levels, GPx, SOD and CAT activities, howbeit, to varying degrees in the heart and kidneys. COG (200mg/kg) was most effective in restoring the blood pressures in the rats to near control levels. CoCl2-induced histopathological lesions including myocardial infarction and inflammation and renal tubular necrosis and inflammation were effectively ameliorated by the treatments administered. This study provides evidence for the protective roles of O. gratissimum and gallic acid by modulation of CoCl2-induced alterations in blood pressure, antioxidant status and pro-apoptotic caspase 8 in Wistar rats.

Gallic acid protects against cyclophosphamide-induced toxicity in testis and epididymis of rats.

The protective role of gallic acid (GA) on reproductive toxicity induced by cyclophosphamide (CPA), an antineoplastic drug, was investigated in male Wistar rats. Sixty rats were grouped into 10 rats per group. Group 1 (control) received distilled water. Rats in groups 2 and 3 received GA alone at 60 and 120 mg kg(-1) for 14 consecutive days, respectively. Group 4 received a single intraperitoneal dose of CPA at 200 mg kg(-1) on day 1. Groups 5 and 6 received a single dose of CPA (200 mg kg(-1) ) intraperitoneally on day 1 followed by treatment with GA at 60 and 120 mg kg(-1) for 14 consecutive days, respectively. In testes and epididymis of the treated rats, CPA administration resulted in significant elevation (P < 0.05) in malondialdehyde (MDA), nitrite and hydrogen peroxide levels. There was a significant decrease in the activities of superoxide dismutase and glutathione-S-transferase. Furthermore, there were significant reductions in plasma luteinising hormone (LH), follicle stimulation hormone (FSH) and testosterone levels, which were accompanied by significant decrease in sperm motility and viability in CPA-treated rats. Histological examination revealed marked testicular and epididymal atrophy in CPA alone treated rats and these aberrations were reversed by GA. In conclusion, GA has capacity to protect against reproductive toxicity induced by cyclophosphamide.

Hematological and serum biochemical indices of West African dwarf goats with foreign body rumen impaction.

Hematological and biochemical parameters were determined in 82 West African Dwarf goats with foreign body rumen impaction (FBR) and 40 normal WAD goats without foreign body rumen impaction (WFBR) in order to evaluate their influence on the etio-pathogenesis of rumen impaction. The mean PCV (26.22%), RBC (9.03 X 106/µL), Hb (8.38g/dl) and MCHC (32.20g/dl) were significantly lower in FBR than in WFBR. The values obtained for serum sodium, potassium, calcium and magnesium in FBR goats were not significantly different from that of WFBR goats. Mean values of serum total protein (4.02gm/dl), phosphorus (3.38mg/dl), glucose (29.33gm/dl), zinc (0.72mmol/L) and copper (0.49mmol/L) in FBR goats were significantly lower than in WFBR goats. The results suggest that foreign body rumen impaction in WAD goats is influenced by some hematological (PCV, RBC, Hb, MCHC) and serum biochemical (total protein, phosphorus, glucose, zinc, copper) parameters and can be used as a basis for formulating preventive measures.