Neuroprotective mechanisms of selenium against arsenic-induced behavioral impairments in rats.

Environmental pollution due to arsenic is associated with several adverse health effects including neurotoxicity in animals and humans. Selenium is a nutritionally essential trace metalloid well documented to elicit compelling pharmacological activities in vitro and in vivo. Report on the influence of selenium on arsenic-mediated behavioral derangement is lacking in literature. Hence, to fill this knowledge gap, rats were either exposed to arsenic per se in drinking water at 60 µg AsO2Na/L or co-administered with inorganic selenium at 0.25 mg/kg or organic selenium diphenyl diselenide (DPDS) at 2.5 mg/kg body weight for 45 successive days. Neurobehavioural data from rats in a new environment using video-tracking software evinced that inorganic and organic forms of selenium significantly (p < 0.05) abrogated arsenic-induced motor and locomotor insufficiencies such as increased negative geotaxis and fecal pellets numbers as well as the diminution in grip strength, body rotation, maximum speed, absolute turn angle and total distance travelled. The augmentation in the behavioral activities in rats co-administered with arsenic and both forms of selenium was substantiated using track and occupancy plots analyses. Selenium mitigated arsenic-induced decreases in glutathione level and acetylcholinesterase activity as well as the increase in oxidative stress and reactive oxygen and nitrogen species. Moreover, selenium diminished inflammatory parameters (myeloperoxidase activity, nitric oxide, tumour necrosis factor alpha and interleukin-1 beta levels), caspase-3 activity and ameliorated histological lesions in the cerebellum, cerebrum and liver of the rats. Collectively, selenium abated arsenic-induced behavioral derangements via anti-inflammation, antioxidant and anti-apoptotic mechanisms in rats.

Selenium abates reproductive dysfunction via attenuation of biometal accumulation, oxido-inflammatory stress and caspase-3 activation in male rats exposed to arsenic.

Frequent exposure to arsenic is well documented to impair reproductive function in humans and animals. Biological significance of inorganic selenium and organoselenium, diphenyl diselenide (DPDS), has been attributed to their pharmacological activities. However, their roles in arsenic-mediated reproductive toxicity is lacking in literature. The present study evaluated the protective effects elicited by selenium and DPDS in arsenic-induced reproductive deficits in rats. Animals were either exposed to arsenic alone in drinking water at 60 µg AsO2Na L-1 or co-treated with selenium at 0.25 mg kg-1 or DPDS at 2.5 mg kg-1 body weight for 45 consecutive days. Results indicated that arsenic-mediated deficits in spermatogenic indices and marker enzymes of testicular function were significantly abrogated in rats co-treated with selenium or DPDS. Additionally, selenium or DPDS co-treatment prevented arsenic-mediated elevation in oxidative stress indices and significantly suppressed arsenic-mediated inflammation evidenced by diminished myeloperoxidase activity, nitric oxide, tumor necrosis factor alpha and interleukin-1 beta levels in hypothalamus, testes and epididymis of the rats. Moreover, selenium or DPDS abrogated arsenic mediated activation of caspase-3 activity and histological lesions in the treated rats. Taken together, selenium or DPDS improved reproductive function in arsenic-exposed rats via suppression of inflammation, oxidative stress and caspase-3 activation in rats.

Chemoprotective effect of Vernonia amygdalina Del. (Astereacea) against 2-acetylaminofluorene-induced hepatotoxicity in rats.

Natural products possessing antioxidant properties play a very crucial role in ameliorating deleterious effects of reactive oxygen species. This study investigated the chemoprotective properties of methanolic extract of Vernonia amygdalina (MEVA) in an experimental model of hepatic oxidative damage induced by 2-acetylaminofluorene (2-AAF). Rats were divided into six groups. Groups 1 and 2 received saline and dimethyl sulfoxide, respectively, and served as controls. Group 3 received MEVA at a dose of 250 mg/kg, while groups 5 and 6 were pretreated for 14 days with MEVA at 250 mg/kg and 500 mg/kg doses before coadministration with 2-AAF at 100 mg/kg for another 7 days. 2-AAF was administered to group 4 for the last 7 days. Animals were killed 24 h after the last administration of 2-AAF. 2-AAF significantly (p < 0.05) induced marked hepatic damage as revealed by increased activities of serum enzymes such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transferase and bilirubin concentration. 2-AAF also elicited decrease in the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione-S-transferase, and glutathione peroxidase, depletion of reduced glutathione, and increase in malondialdehyde levels. The activities of glucose-6-phosphatase and 5'-nucleotidase were also depleted. MEVA at 250 mg/kg and 500 mg/kg significantly (p < 0.05) ameliorated the oxidative damage, functional impairments, and histopathological changes associated with 2-AAF toxicity by reducing the activities of serum enzymes, upregulating the antioxidant defense enzymes and glutathione with decrease in malondialdehyde level. In this study, the revealed ameliorative and hepatoprotective effects of MEVA against 2-AAF-induced toxicity may be due to its antioxidant and free-radical scavenging activities, thus suggesting its usefulness as a possible chemoprophylactic agent.

An inventory of plants commonly used in the treatment of some disease conditions in Ogbomoso, South West, Nigeria.

ETHNOPHARMACOLOGICAL RELEVANCE: This study was designed to take an inventory of medicinal plants, recipes and methods commonly used traditionally to treat some cardiovascular and inflammatory diseases in five local government areas in Ogbomoso, Oyo State, Nigeria. MATERIAL AND METHODS: First-hand field survey through semi-structured questionnaire was employed in the 5 months study. RESULTS: A total of 101 plant species (medicinal plants (80.90%), spices (17.5%) and vegetables (1.53%)) belonging to 51 different families were mentioned for the treatment of various types of cardiovascular and inflammatory diseases. The survey revealed that 51.5% of the plants mentioned are used for the management of inflammatory diseases, 34.7% for the treatment of cardiovascular diseases and 11.9% of the plants are used for the treatment of both diseases. Euphorbiaceae (7.9%) are the most frequently used families of plants for the treatment of the various types of diseases mentioned, followed by Caesalpiaceae, (4.9%), Apocynoceae (4.9%) and Poaceae (4.9%). Fifty-nine recipes are usually prepared for the treatment of the six types of inflammatory diseases while twenty-three recipes are reportedly used for the treatment of the four types of cardiovascular diseases mentioned in this study. The recipes covered in the survey were mostly prepared from leaves (37.6%) and roots (23.8%) decoction or infusions. Medications are mostly administered orally with few numbers of the recipes showing side effect. CONCLUSION: The study has documented indigenous plants in Ogbomoso as a potential source for the development of new drugs for the treatment of cardiovascular and inflammatory diseases.

Ethnobotanical survey of medicinal plants used in the treatment of malaria in Ogbomoso, Southwest Nigeria.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria infection is the second largest killer disease after HIV in Nigeria. Failure of the orthodox medications due to drug adulteration, high cost of procurement of antimalarial drugs and inconvenience experienced in the use of high dosage of the new antimalarial drug combination therapy has turned the attention of the people in the world towards the use of local herbs. MATERIALS AND METHODS: An ethnobotanical survey of medicinal plants used by the indigenous people of Ogbomoso for the treatment of malaria infection was conducted. Investigations were carried out on the names of plants, their parts (leaf, stem or root) used, method of preparing herbal antimalarial remedies, likely side effect and how it is administered were recorded through the use of a structured questionnaire. RESULTS: The results of the survey revealed that 40 plant species from 32 plant families were mostly used for treating malaria infection in Ogbomoso. Twenty-three different antimalarial recipes were mentioned in the survey. The Asteraceae and Anacardinceae were the most represented plant families followed by Malvaceae, Solanaceae, Annonaceae, Poaceae, Rutaceae and Meliaceae. The leaf and the stem bark have been the most frequently used plant parts while concoction and decoction were the most common method of preparation. Treatment regimens of malaria generally included drinking, bathing and steam inhalation of the aqueous herbal preparations for 5-7 days or until symptoms of malaria disappear. About 53% of the plants mentioned in the survey had side effect. CONCLUSIONS: Hence, the need for documentation of these plants for further investigation becomes necessary.

Repeated oral administration of Febi super bitters correlated with some tissue toxicity in male Wistar rat.

This study investigated the toxic implication of Febi Super Bitters in Male Wistar rats because of upsurge in its usage for therapeutic reasons. Eighteen rats, with an average weight of 86.2 +/- 4.43 g, were randomly distributed into three equal groups of six rats per group. The rats were acclimatized for 14 days and 0.308 and 0.462 mL kg(-1) b.wt. of Febi super bitters were administered daily to groups B and C, respectively for 56 days, while group A received distilled water. The toxicity of the herbal bitter was assessed by determining the activities of Lactate Dehydrogenate (LDH), Alkaline Phosphatase (ALP) and Acid Phosphatase (ACP) in the liver, kidney, small intestine, heart, brain, lungs, spleen, serum and histological studies on the organs. The activities of LDH were significantly reduced (p < 0.05) in the liver, small intestine and lung, while it increased significantly (p < 0.05) in the brain and serum. ALP activities decreased significantly (p < 0.05) in the liver, kidney, small intestine and heart but increased (p < 0.05) in brain, spleen and serum. ACP activities in the liver and kidney were decreased (p<0.05) and increased significantly (p < 0.05) in the spleen and serum. Increases were significantly recorded in serum total bilirubin, unconjugated bilirubin, total protein and globulin, while reductions were recorded in the conjugated bilirubin and A/G (p < 0.05). Histoarchitecture of the lungs, spleen and small intestine revealed marked cellular distortions. In the light of these findings, the habitual consumption of Febi super bitters is not recommended as it has underlined toxicity in some vital internal organs.

Immunomodulatory activities of Yoyo bitters: recommended dose precipitated inflammatory responses in male Wistar rats.

This study investigated the immunomodulatory capabilities of the sub-chronic administration of Yoyo bitters in male Wistar rats. Eighteen rats weighing 86.2 +/- 4.43 g were randomly picked into three equal groups. The rats were acclimatized for 14 days, after which 0.308 and 0.462 mL kg(-1) b.wt. of Yoyo bitters were administered once daily to groups B and C respectively for 56 days, while group A received distilled water. The feed intake, body weight, blood glucose, interleukin 2 (IL-2), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha), haematological parameters, serum lipid profile and uric acid, liver reduced glutathione and malodialdehyde were determined. The feed intake, body weight and blood glucose concentrations were reduced (p < 0.05) at the doses. No changes were recorded in the concentration of serum IL-2 (p > 0.05), but IL-6 decreased (p < 0.05) in group B and increased (p < 0.05) in group C, while TNF-alpha were increased (p < 0.05) dose dependent. The haematological parameters were decreased at all the doses (p < 0.05), except the ESR, WBC and lymphocytes that were increased (p < 0.05) and platelets in group C (p < 0.05). The serum total cholesterol, TAG, LDL-C and atherogenic index were decreased (p < 0.05) and HDL-C increased (p < 0.05) in group B only. Serum uric acid was reduced (p < 0.05) in group B, but increased in group C with the concentration of liver MDA (p < 0.05). The study, therefore, established that a dose lower than the manufacturer's recommended dose presented the desired immunomodulatory activities and the habitual use of Yoyo bitters at the adult recommended dose calls for caution.

Modulatory effect of methanolic extract of Vernonia amygdalina (MEVA) on tert-butyl hydroperoxide-induced erythrocyte haemolysis.

Reactive oxygen species (ROS) have been implicated in the aetiology of several pathological and degenerative diseases. The protective effect of natural products possessing antioxidant properties has played a crucial role in ameliorating these deleterious effects. This study investigated the chemoprotective properties of the methanolic extract of Vernonia amygdalina (MEVA) in an experimental model of tert-butyl hydroperoxide (t-BHP)-induced human erythrocyte lysis in vitro. Haemolysis was induced by incubating erythrocytes with t-BHP (2 and 3 mM) in vitro. Samples of erythrocyte suspensions were removed at different intervals over a 6-h period, and the degree of haemolysis was measured. The anti-haemolytic effect of MEVA at 25-150 µg ml(-1) concentrations on the samples were assessed and compared with Triton X-100. Administration of t-BHP at 2- and 3-mM concentrations significantly (p < 0.05) induced erythrocyte lysis by 37.5% and 31.4%, respectively. The addition of MEVA, however, reduced t-BHP-induced erythrocyte lysis significantly (p < 0.05) by 39.3%, 48.4%, 67.3% and 73.4% at 25, 50, 100 and 150 µg ml(-1) concentrations, respectively. MEVA likewise protected against t-BHP-induced lipid peroxidation significantly (p < 0.05) at 100 and 150 µg ml(-1) by the fourth hour and non-significantly (p > 0.05) at all concentrations by the sixth hour. The reduced glutathione level was, however, increased with the administration of t-BHP, while a delayed addition of MEVA had no protective effect on the t-BHP-induced cell lysis. These findings therefore suggest that MEVA may have protective antioxidant properties, making it suitable for incorporation into food and drug products.

Protection against 2- acetyl aminofluorene-induced toxicity in mice by garlic (Allium sativum), bitter kola (Garcina kola seed) and honey.

The effects of honey (Hoc) and aqueous suspensions of garlic (Allium sativum) (Ga) and bitter kola (Garcina kola seed) (Bi) on the toxicities induced by 2-acetylaminofluorene (2-AAF) a model carcinogen, were investigated in mice. The animals were dosed for seven consecutive days with Ho, Ga and Bi as dietary supplements. They were then challenged with a single intraperitoneal (i.p.) dose of 2-AAF at 50 mg/kg bd. wt on the seventh day. The degree of clastogenicity was assessed using the mouse micronucleus assay while liver damage was monitored by measuring the level of gamma glutamyltransferase (gamma-GT) in serum and liver homogenates respectively. The results revealed that 2-AAF induced micronuclei formation in the polychromatic erythrocytes (PCEs) of the bone marrow by about five fold in comparison to the PCEs formed in control mice. Ho, Ga, and Bi also induced micronucleus formation on their own. However. feeding of any of Ho, Ga or Bi and the administration (i.p) of 2-AAF reduced significantly, the ability of 2-AAF to induce micronuclei formation in the order Ho>Ga>Bi. Furthermore, 2-AAF induced gamma-GT activity in the serum and liver homogenate by about two and a half and three folds respectively. A combination of 2-AAF and any of Ga or Bi or Ho significantly decreased 2-AAF-induced activity of gamma-GT in the order Ho>Bi>Ga (serum) and Bi>Ga=Ho (liver). These findings suggest that honey, garlic and bitter kola protect against 2-AAF-induced gamma-GTactivity and micronuleated PCEs formation.

Anticlastogenic effects of Hibiscus sabdariffa fruits against sodium arsenite-induced micronuclei formation in erythrocytes in mouse bone marrow.

An in vivo micronucleus assay using albino mice was used to examine the anticlastogenic effects of a crude aqueous extract of Hibiscus sabdariffa fruits in bone marrow cells of mice. Various doses of freshly prepared crude extract of Hibiscus sabdariffa (50, 100 and 150 mg/kg b.w.) were given by gavaging to male laboratory bred Swiss albino mice for 7 days as a dietary supplement followed by a single dose of sodium arsenite (2.5 mg/kg b.w.) After 24 h, the animals were killed and bone marrow smears were prepared and stained in Giemsa. The results show that sodium arsenite effectively induced micronuclei in polychromatic erythrocytes (PCEs). Administration of a crude extract of Hibiscus sabdariffa led to a significant reduction of micronuclei in PCEs. The results also show that a combination of Hibiscus sabdariffa and sodium arsenite reduced significantly the frequencies of micronucleated PCEs induced by sodium arsenite.