Effect of Metaswitch® dietary supplement on anthropometric parameters, serum lipids, glucose level, oxidative stress and in vivo antioxidant properties in high fat diet-induced overweight Sprague Dawley rats.

PURPOSE: Obesity and overweight are metabolic disorders associated with oxidative stress, and risk factors for many chronic diseases. We sought to investigate the effects of Metaswitch dietary supplement on weight gain and associated acute metabolic alterations in a high-fat diet-induced overweight rat model. METHODS: Female Sprague Dawley (SD) rats were put into 6 groups. Control groups were fed normal (NCD) or high-fat diet (HFD). Treatment groups on HFD receieved 3 different daily doses of Metaswitch for 3 weeks. Another group on HFD received Slimrite® (phenylpropanolamine), a standard drug. Rats on HFD also received cyproheptadine to stimulate appetite. Food consumption and anthropometric parameters were determined weekly. Serum lipids, glucose level, hepatic lipid peroxidation, and antioxidant activity were used to assess overweight in rats. RESULTS: Food intake remained relatively constant among groups. Rats on HFD had significantly increased body weight compared to rats fed NCD. Metaswitch significantly prevented weight gain; this effect was greater or similar to rats administered Slimrite, but was not dose-dependant. No significant changes occurred in the levels of serum lipids and glucose among the groups. However, serum triglyceride (TG) was significantly increased. The TG/HDL-C ratio revealed significant metabolic alterations which was prevented by Metaswitch. Catalase activity was significantly decreased in the HFD untreated group but was restored in Metaswitch-treated groups. CONCLUSIONS: A 3-week HFD regimen with cyproheptadine supplementation in female SD rats resulted in a significant increase in body weight and acute metabolic alterations. The aforementioned changes were found to have been prevented with the administration of Metaswitch.

Genotoxicity, nitric oxide level modulation and cardio-protective potential of Kalanchoe Integra Var. Crenata (Andr.) Cuf Leaves in murine models.

ETHNOPHARMACOLOGICAL RELEVANCE: Advancement in cancer therapy has improved survival among patients. However, use of anticancer drugs like anthracyclines (e.g., doxorubicin) is not without adverse effects. Notable among adverse effects of doxorubicin (DOX) is cardiotoxicity, which ranges from mild transient blood pressure changes to potentially serious heart failure. Anecdotal reports suggest that Kalanchoe integra (KI) may have cardio-protective potential. AIMS OF THE STUDY: This study sought to determine the cardio-protective potential of KI against doxorubicin-induced cardiotoxicity and also examined any possible genotoxic potential of KI in selected organs. Additionally, the nitric oxide modulatory potential of KI was assessed. MATERIALS AND METHODS: The leaves of KI were collected, air-dried, pulverised and extracted using 70% ethanol. High-performance liquid chromatography (HPLC) fingerprinting was done for KI. Also, the single-cell gel electrophoresis assay (Comet assay) was employed to ascertain the genotoxic potential of KI. In assessment of cardio-protective potential of KI against doxorubicin-induced cardiotoxicity, a total of 42 female Sprague-Dawley rats were put into 7 groups (n = 6). Group I: vehicle control, received normal saline (1 mL/kg p.o) for 30 days. Group II: toxic control, received DOX (20 mg/kg i.p.) once on the 29th day. Group III: KI control, received KI (300 mg/kg p.o) for 30 days. Group IV: vitamin E control, received vitamin E (100 mg/kg p.o) for 30 days. Group V: KI treated-1, received KI (300 mg/kg p.o) for 30 days and DOX (20 mg/kg i.p) on the 29th day. Group VI: KI treated-2, received KI (600 mg/kg p.o) for 30 days and DOX (20 mg/kg i.p) on the 29th day. Group VII: vitamin E treated, received vitamin E (100 mg/kg p.o) for 30 days and DOX (20 mg/kg i.p) on the 29th day. Thirty-six (36) hours after last administration, rats were sacrificed. Blood samples were taken via cardiac puncture to determine levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), lactate dehydrogenase (LDH), enzymatic antioxidants such as glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Nitric oxide level was also determined. Hearts of rats in each group were excised and taken through histopathological examination. RESULTS: In the HPLC fingerprint analysis, 13 peaks were identified, and peak with retention time of 24.0 min had the highest peak area (3.223 x104 mAU). Comet assay showed that the KI extract was non-genotoxic. Pretreatment with KI protected rats against doxorubicin-induced cardiotoxicity as evidenced by the low levels of AST, ALT, ALP, CK and LDH compared with the controls (p < 0.05). SOD, CAT and GPX levels were also high for rats administered KI extracts, further showing that KI protected rats against doxorubicin-induced cardiotoxicity. KI also inhibited nitric oxide levels at 300 mg/kg and 600 mg/kg effective doses. Histological examination revealed that rats pretreated with KI showed no signs of abnormal myocardial fibres (shape, size and configuration). CONCLUSION: Ethanolic (70%) leaf extract of KI showed no genotoxic potential and possessed cardioprotective effects against doxorubicin-induced cardiotoxicity in Sprague-Dawley rats. KI also inhibited nitric oxide production, thus, a potential nitric oxide scavenger.

Contrasting Hygiene-Related Gastrointestinal Infections and Stress-Related Diseases at a Primary Health Care Facility within a Sub-Saharan African City: Before and during the COVID-19 Pandemic.

BACKGROUND: With the advent of the COVID-19 pandemic caused by SARS-CoV-2, protocols such as social distancing and upscaling of hygiene practices were implemented to limit the spread of the disease. Meanwhile, along with COVID-19 came stress due to restrictions on movement, trade and transport, and closure of schools, among others. AIM: This study compared the prevalence of hygiene-related gastrointestinal infections and stress-related diseases before (March 2019-February 2020) and during (March 2020-February 2021) the COVID-19 pandemic. METHODOLOGY: This was a retrospective single-center review of deidentified patient data from the Korle Bu Polyclinic, Accra, Ghana. RESULTS: Comparing the pre-COVID-19 era to the COVID-19 era, there was a statistically nonsignificant change in the number of cases and prevalence of gastroenteritis and enteric fever (p = 0.084 and 0.081, respectively), although for gastroenteritis, the prevalence was higher for the pre-COVID-19 era compared to during COVID-19 by 1.8 per 1000 cases, while that of enteric fever was higher during the COVID-19 era compared to the pre-COVID-19 era by 1.0 per 1000 cases. Of the stress-related diseases, statistically significant increases in the prevalence of anxiety disorders (p = 0.028), insomnia (p = 0.001), and headache (p = 0.010), were noted, with 2.3, 5.5, and 2.4 per 1000 cases, respectively. There were more female cases than male cases recorded for depression (p = 0.001), headache (p = 0.010), and hypertension (p = 0.001) during the pandemic, and these were statistically significant. CONCLUSION: During the pandemic, a significant increase in the prevalence of stress-related diseases was observed. However, a statistically nonsignificant change was recorded for gastrointestinal infections, with females reporting more of these disorders. Consequently, it is important to strengthen the capacity for managing stress-related conditions alongside diseases that cause pandemics when they arise.

Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha.

INTRODUCTION: Major depressive disorder is often associated with suicidal tendencies, and this condition accentuates the need for rapid-acting antidepressants. We previously reported that Alkaloids (ALK) from Trichilia monadelpha possess antidepressant action in acute animal models of depression and that this effect is mediated through the monoamine and L-arginine-NO-cGMP pathways. This study investigated the possible rapid-onset antidepressant effect of ALK from T. monadelpha and its connection with the glycine/NMDA receptor pathway. METHODS: The onset of ALK action from T. monadelpha was evaluated using the Open Space Swim Test (OSST), a chronic model of depression. The modified forced swimming and tail suspension tests were used to assess the effect of the ALK on the glycine/NMDA receptor pathway. The Instutute of Cancer Research (ICR) mice were treated with either ALK (30-300 mg/kg, orally [PO]), imipramine (3-30 mg/kg, PO), fluoxetine (3-30 mg/kg, PO), or saline. To identify the role of glycine/NMDA receptor pathway in the effect of ALK, we pretreated mice with a partial agonist of the glycine/NMDA receptor, D-cycloserine (2.5 mg/kg, intraperitoneally [IP]), and an agonist of glycine/NMDA receptor, D-serine (600 mg/kg, IP), before ALK administration. RESULTS: ALK reversed immobility in mice after the second day of drug treatment in the OSST. In contrast, there was a delay in the effects induced by fluoxetine and imipramine. ALK also increased mean swimming and climbing scores in mice. ALK was more efficacious than imipramine and fluoxetine in reducing immobility and increasing distance traveled. It is noteworthy that ALK was less potent than fluoxetine and imipramine. D-cycloserine potentiated mobility observed in the ALK- and fluoxetine-treated mice. In contrast, D-serine decreased mobility in the ALK-treated mice. CONCLUSION: The study results suggest that ALK from T. monadelpha exhibits rapid antidepressant action in mice, and the glycine/NMDA receptor pathway possibly mediates the observed effect.

Toxicity, mutagenicity and trace metal constituent of Termitomyces schimperi (Pat.) R. Heim (Lyophyllaceae) and kaolin, a recipe used traditionally in cancer management in Cote d'Ivoire.

ETHNOPHARMACOLOGICAL RELEVANCE: Some local communities in Cote d'Ivoire use the mushroom Termitomyces schimperi combined with kaolin (TSK) to manage various cancers in patients. However, there is a paucity of data on toxicity, mutagenicity and trace metal constituent of TSK. AIM OF THE STUDY: We sought to investigate the acute and sub-chronic toxicities, mutagenic potential, and trace metal constituents of TSK. MATERIALS AND METHODS: To assess acute toxicity, single doses (1000, 3000 and 5000 mg/kg) of aqueous extract of TSK were administrated per os to Sprague Dawley (SD) rats on Day 1. The rats were then monitored for 13 consecutive days. Sub-chronic toxicity was evaluated by daily administration of 200 and 500 mg/kg of the extract per os for 90 consecutive days. SD rats used as control received distilled water. Signs of toxicity, changes in body weight and mortality were monitored. After the aforementioned monitoring processes, rats were sacrificed and blood collected for full blood count and biochemistry analysis. Animal organs were also collected for histopathological examination. The mutagenic potential of the aqueous extract of TSK (10000 µg/mL) on TA98 Salmonella typhimurium was estimated. Additionally, energy-dispersive X-ray fluorescence (ED-XRF) method was employed to determine trace metal constituents of TSK. RESULTS: Single-dose administration of 5000 mg/kg of TSK did not cause any death in the SD rats; thus, LD50 was above 5000 mg/kg. Administration of 1000 and 3000 mg/kg of the aqueous extract of TSK did not cause any significant change in behaviour and body weight of SD rats during the 14-day monitoring period. However, the mean corpuscular volume and the mean corpuscular haemoglobin concentration increased significantly (p < 0.01) among rats administered 1000 and 3000 mg/kg of TSK. There was a significant increase (p < 0.0001) in alanine transaminase levels in rats administered 1000 and 3000 mg/kg of TSK extract compared with control. Conversely, there was a significant decrease (p=0.0122) in serum creatine level among rats administered 1000 and 3000 mg/kg of TSK extract compared with control. After 14 days, there were minimal changes with isolated organs of TSK-treated and control rats. Furthermore, 90-day treatment with extract of TSK caused no significant change in parameters assessed. TSK induced frameshift gene mutation in S. typhimurium before (p < 0.05) and after metabolic activation (p < 0.001). Elemental analysis of TSK revealed the presence of toxic (aluminium) or potentially toxic (silver, rabidium, titanium and zirconium) elements. CONCLUSIONS: The aqueous extract of TSK showed no toxicity (acute and sub-chronic) at doses tested. These findings are consistent with the absence of heavy metals (i.e., cadmium) and potentially toxic elements (i.e., uranium) in TSK samples analysed. TSK showed some level of mutagenic potential. Further mutagenic and chronic toxicity studies on TSK are required.

Ethanolic extract of Nymphaea lotus L. (Nymphaeaceae) leaves exhibits in vitro antioxidant, in vivo anti-inflammatory and cytotoxic activities on Jurkat and MCF-7 cancer cell lines.

BACKGROUND: Nymphaea lotus L. (N. lotus) is an aquatic plant with anecdotal reports suggesting its use in the traditional management of cancer. However, there is a paucity of data on the antioxidant, anti-inflammatory and cytotoxic properties of N. lotus in relation to its phytochemical and elemental contents. This study aimed at determining the antioxidant, anti-inflammatory and cytotoxic properties of the hydro-ethanolic extract of N. lotus leaves (NLE), and its phenolic, flavonoid and elemental constituents. METHODS: The antioxidant property of NLE was determined using total phenolic and flavonoid, DPPH radical scavenging, lipid peroxidation and reducing power assays. The anti-inflammatory activity of NLE (100-250-500 mg/kg), diclofenac and hydrocortisone (positive controls) were determined by paw oedema and skin prick tests in Sprague Dawley rats. Also, the erythrocyte sedimentation rate (ESR) was determined by Westergren method. The macro/micro-elements content was determined by the XRF method. The cytotoxic property of NLE was determined by the MTT assay, on two cancer cell lines (MCF-7 and Jurkat) and compared to a normal cell line (Chang liver). Inhibitory concentrations were determined as IC50 values (±SEM). RESULTS: The extract had appreciable levels of phenolic and flavonoids compounds and was two-fold more potent in scavenging DPPH radicals than Butylated hydroxytoluene (BHT). However, NLE was three- and six-fold less potent than ascorbic acid and BHT, respectively, in reducing Fe3+ to Fe2+. The extract was six-fold more potent than gallic acid in inhibiting lipid peroxidation. The extract caused a dose-dependent decrease in rat paw oedema sizes, comparable to diclofenac, and a significant decrease in wheel diameters and ESR. The elemental analysis revealed relevant concentrations of Mg2+, P2+, S2+, K2+, Mn+, Fe+, Cu+, Zn+ and Cd+. The extract exhibited cytotoxic activity on both MCF-7 (IC50 = 155.00 µg/ml) and Jurkat (IC50 = 87.29 µg/ml), with higher selectivity for Jurkat cell line. Interestingly, the extract showed low cytotoxicity to the normal Chang liver cell line (IC50 = 204.20 µg/ml). CONCLUSION: N. lotus leaves extract exhibited high antioxidant, anti-inflammatory and cancer-cell-specific cytotoxic properties. These aforementioned activities could be attributed to its phenolic, flavonoid and elemental constituents.

Effect of Cellgevity® Supplement on Selected Rat Liver Cytochrome P450 Enzyme Activity and Pharmacokinetic Parameters of Carbamazepine.

BACKGROUND: There is considerable evidence that many patients concurrently administer dietary supplements with conventional drugs, creating a risk for potential drug-supplement interaction. The aim of this study was to determine the effect of Cellgevity® supplement on selected rat liver cytochrome P450 (CYP) enzymes. Also, based on our previous finding, we sought to determine the effect of Cellgevity® on the pharmacokinetics of carbamazepine, a CYP3A4 substrate. METHODS: Male Sprague-Dawley (SD) rats were randomly put into 5 groups and administered either distilled water (negative control), Cellgevity® (3 separate doses), or phenobarbital (positive control), per os. Modulation of liver CYP enzyme activity was evaluated after 30 days of treatment, using probe substrates, spectroscopic, and high-performance liquid chromatographic methods. In the pharmacokinetic study, 12 SD rats were put into 2 groups and administered carbamazepine plus normal saline (group 1) or carbamazepine plus Cellgevity® (group 2), per os, both over a period of 14 days. Blood samples from rats in the same group were collected after treatment. Serum samples were prepared and pooled together at each specific sampling time point. Levels of carbamazepine were determined using a fluorescence polarization immunoassay. RESULTS: Activities of rat liver CYP1A1/2, CYP2C9, and CYP2D6 were significantly increased by Cellgevity® after 30-day treatment. Pharmacokinetic parameters for rats administered carbamazepine with Cellgevity® vis-a-vis carbamazepine with normal saline were as follows: C max; 20 µmol/L vs 11 µmol/L, AUC0⟶24; 347 µmol h/L vs 170 µmol h/L, K e; 0.28 h-1 vs 0.41 h-1, and t 1/2; 2.3 h vs 1.7 h, respectively. CONCLUSIONS: Cellgevity® increased the activity of rat CYP1A1/2, CYP2C9, and CYP2D6 enzymes and was found to alter the pharmacokinetics of carbamazepine in rats.

Ethnomedicinal survey and mutagenic studies of plants used in Accra metropolis, Ghana.

ETHNOPHARMACOLOGICAL RELEVANCE: Majority of people living in Ghana and many other developing countries rely on traditional medicinal plants for their primary healthcare. These plants are used either alone or in combination to manage a wide range of ailments. However, most of these plants have not been investigated for their mutagenic effects. AIM OF THE STUDY: This study, therefore aimed at evaluating the mutagenic activity of the most frequently used medicinal plants amongst Ghanaians living within the Accra metropolis, Ghana. MATERIALS AND METHODS: Validated questionnaires were administered to 53 herbalists and herbal medicines dealers in the Makola, Madina and Nima communities. Plants that were identified as being frequently used were investigated for their mutagenicity using the Ames test. RESULTS: A total of 110 medicinal plants belonging to 53 families were identified as most frequently used plants in the study sites. These are used to treat various ailments including gastric ulcer, fever, malaria, male impotence, diabetes, typhoid, high blood pressure and candidiasis. Thirteen samples (52%) showed moderate to high mutagenicity in the TA 100 bacterial strain before and after metabolism with rat liver enzyme. CONCLUSIONS: The study showed that over half of the frequently used medicinal plants showed moderate to high mutagenicity before and after metabolism at the concentration of a 100 µg/mL. This may have implications for the safety of those who use them to manage diseases. These findings will suggest the need for an in-depth study of the mutagenic potentials of plants commonly used by indigenous people and more especially for those exhibiting high mutagenicity in this study.

Serum Iron Levels and Copper-to-Zinc Ratio in Sickle Cell Disease.

Background and Objectives: Altered copper and zinc homeostasis may influence the antioxidant defense system and consequently lead to oxidative stress and associated complications in sickle cell disease (SCD) patients. Iron levels have been reported to increase in sickle cell patients due to frequent blood transfusion, chronic intravenous haemolysis and increased absorption of iron from the gastrointestinal tract. These elevated levels of iron may also lead to extensive oxidative damage. The current study evaluated serum levels of iron, copper and zinc in SCD patients and "healthy" controls. Materials and Methods: The study was a cross-sectional one, comprising 90 SCD patients with Haemoglobin SS and Haemoglobin SC genotypes and 50 HbAA "healthy" controls. Serum levels of iron, copper and zinc were measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd, VIC, Australia). Copper and zinc ratios were calculated and analyzed. Results: Serum levels of iron and copper were significantly elevated in the SCD patients, compared to their "healthy" counterparts (p < 0.001). These levels were further increased in patients with haemoglobin SS in vaso-occlusive crises (HbSS VOCs). Serum zinc levels were, however, significantly lower in the SCD patients, particularly during vaso-occlusion. The copper-to-zinc ratio was also found to be significantly higher in the SCD patients. Conclusion: Elevated copper-to-zinc ratio may be a biomarker of sickle cell oxidative stress and associated complications. The ratio may also be informative for the management of sickle cell oxidative burden. The significantly lower levels of zinc in the SCD patients may warrant zinc supplementation.

In Vitro Antioxidant Potential and Effect of a Glutathione-Enhancer Dietary Supplement on Selected Rat Liver Cytochrome P450 Enzyme Activity.

BACKGROUND: There is considerable evidence that many people take dietary supplements including those of herbal origin as an alternative therapy to improve their health. One such supplement, with an amalgam of constituents, is CellGevity®. However, the effect of this dietary supplement on drug-metabolizing enzymes is poorly understood, as it has not been studied extensively. Therefore, we investigated the effect of CellGevity dietary supplement on selected rat liver microsomal cytochrome P450 (CYP) enzymes, the most common drug-metabolizing enzymes. We also determined the total antioxidant potential of this dietary supplement in vitro. METHODS: To determine the antioxidant potential of CellGevity dietary supplement, 2,2-diphenyl-2-picryl-hydrazyl (DPPH), total phenolic, and flavonoid assays were used after initial preparation of a solution form of the supplement (low dose, LD; 4 mg/kg and high dose, HD; 8 mg/kg). Rats received oral administration of these doses of the supplement for 7 days, after which the effect of the supplement on selected liver CYP enzymes was assessed using probe substrates and spectroscopic and high-performance liquid chromatographic methods. Rats which received daily administration of 80 mg/kg of phenobarbitone and distilled water served as positive and negative controls, respectively. RESULTS: The IC50 value of the supplement 0.34 ± 0.07 mg/ml compared to 0.076 ± 0.03 mg/ml of the BHT (positive control). The total phenolic content of the supplement at a concentration of 2.5 mg/ml was 34.97 g gallic acid equivalent (GAE)/100 g while its total flavonoid content at a concentration of 2.5 mg/ml was 6 g quercetin equivalent (QE)/100 g. The supplement significantly inhibited rat CYP2B1/2B2 (LDT 92.4%; HDT 100%), CYP3A4 (LDT 81.2%; HDT 71.7%), and CYP2C9 (LDT 21.7%; HDT 28.5%) while it had no significant inhibitory effect on CYPs 1A1/1A2, CYP1A2, and CYP2D6. CONCLUSION: CellGevity dietary supplement possesses moderate antioxidant activity in vitro and has an inhibitory effect on selected rat liver CYP enzymes, suggesting its potential interaction with drugs metabolized by CYP enzymes.

Antidepressant Potentials of Components from Trichilia monadelpha (Thonn.) J.J. de Wilde in Murine Models.

Trichilia monadelpha is a common medicinal plant used traditionally in treating central nervous system conditions such as epilepsy, depression, pain, and psychosis. In this study, the antidepressant-like effect of crude extracts of the stem bark of T. monadelpha was investigated using two classical murine models, forced swimming test (FST) and tail suspension test (TST). The extracts, petroleum ether, ethyl acetate, and hydroethanolic extracts (30-300 mg/kg, p.o.), standard drug (imipramine; fluoxetine, 3-30 mg/kg, p.o.), and saline (vehicle) were given to mice one hour prior to the acute study. In a separate experiment the components (flavonoids, saponins, alkaloids, tannins, and terpenoids; 30-300 mg/kg, p.o.) from the most efficacious extract fraction were screened to ascertain which components possessed the antidepressant effect. All the extracts and components significantly induced a decline in immobility in the FST and TST, indicative of an antidepressant-like activity. The extracts and some components showed increase in swimming and climbing in the FST as well as a significant enhancement in swinging and/or curling scores in the TST, suggesting a possible involvement of monoaminergic and/or opioidergic activity. This study reveals the antidepressant-like potential of the stem bark extracts and components of T. monadelpha.

Hematological changes and nitric oxide levels accompanying high-dose artemether-lumefantrine administration in male guinea pigs: Effect of unsweetened natural cocoa powder.

BACKGROUND: Unsweetened natural cocoa powder (UNCP), prepared after removal of the cocoa butter, is a common beverage in Ghana. It possesses antimalarial prophylactic property and has a beneficial effect on blood components. AIM: The aim of this study was to determine whether regular dietary supplement of UNCP mitigates high-dose (HD) artemether-lumefantrine (A-L)-induced hematological disorders and to determine the effect on nitric oxide (NO) levels. MATERIALS AND METHODS: Adult male guinea pigs (300 g - 350 g) were randomly divided into 5 groups of 6 guinea pigs each. Among the 5 groups, 3 groups were treated with UNCP (300, 900, and 1500 mg/kg body weight) for 14 days. A-L (75 mg/kg) was administered from the 12th to 14th day. One of the remaining 2 groups received distilled water only, i.e., vehicle control group (VCG) while the other received 75 mg/kg A-L only, i.e., negative control group (NCG). Blood samples from all groups were obtained by cardiac puncture (day 15) followed by hematological and NO analysis. RESULTS: A-L reduced white blood cells (WBC) by 31.87%, lymphocyte count by 45.99%, hemoglobin by 11.72%, hematocrit by 18.56%, and platelet count by 33.08% in the NCG. Administration of various doses of UNCP increased WBC and lymphocyte count (P > 0.05) compared to the NCG. UNCP and A-L combination caused an increase in NO levels when compared to the VCG. CONCLUSION: Regular consumption of UNCP by guinea pigs increases plasma NO and restores some hematological disorders induced by a 3-day HD A-L administration.

Long-term continuous administration of a hydro-ethanolic extract of Synedrella nodiflora (L) Gaertn in male Sprague-Dawley rats: biochemical, haematological and histopathological changes.

BACKGROUND: Conflicting reports about the toxicity of Synedrella nodiflora (L) Gaertn (family Asteraceae), a plant traditionally used in Ghana for the management of epilepsy, abound in literature. The present study evaluates the effect of a 90-day continuous oral administration of a hydro-ethanolic whole plant extract of Synedrella nodiflora (SNE) in male Sprague-Dawley rats. METHODS: The toxicological evaluation of the extract (100, 300 and 1000 mgkg-1) was focused on haematological, serum biochemical parameters and histopathological changes of some isolated organs. RESULTS: The extract produced no mortality in the rats treated during the study period. Only SNE 100 mgkg-1 produced significant decrease in white blood cell and neutrophil counts and an increase in albumin, globulin, total bilirubin, total protein and potassium levels. The higher doses (SNE 300 and 1000 mgkg-1) had no significant effect on all the haematological and biochemical parameters measured. Histopathological assessment of the liver, kidney and heart revealed no abnormalities in rats treated with the extracts. Only the SNE 1000 mgkg-1 produced distortions of the branching arrangements of the myocardial fibres and a congested vessel which indicates a healed infarction. CONCLUSIONS: The findings suggest hydro-ethanolic extract of Synedrella nodiflora (L) Gaertn generally has a low toxicity profile following a 90-day continuous oral administration in male Sprague-Dawley rats under the present laboratory conditions. However patients with renal or cardiac problems should use the plant with caution. FUNDING: Jointly supported by the International Foundation for Science, Stockholm, Sweden, through a grant (# F/5191-1) to Dr. Patrick Amoateng and the Office of Research, Innovation and Development (ORID), University of Ghana, Accra, Ghana, grant awarded to Dr. Patrick Amoateng (reference number: URF/6/ILG-002/2012-2013).

Macro- and Microelemental Composition and Toxicity of Unsweetened Natural Cocoa Powder in Sprague-Dawley Rats.

Unsweetened natural cocoa powder (UNCP) is a pulverized high-grade powder of compressed solid blocks which remains after extraction. Little scientific data is available concerning its safety despite the presence of potential toxic elements. Elemental composition in UNCP was analyzed with ED-XRF spectroscopy. Single oral high dose toxicity study was conducted on adult male Sprague-Dawley rats (150 g) by the limit test method. One group received water and the test group 2000 mg/kg UNCP. All animals were observed for 14 days and then euthanized for haematological, biochemical, and histopathological examinations. Thirty-eight (38) elements were found in UNCP. There was an increase in HDL cholesterol (p < 0.05), reduction in LDL cholesterol (p > 0.05), alkaline phosphatase (p < 0.05), and creatinine levels, and slight increase in urea levels (p > 0.05). Haematological changes were not significant. Histopathological analysis showed no toxic effect on the heart, liver, kidney, lungs, testis, and spleen. Intestinal erosion was observed in the test group. UNCP appears to be relatively safe when taken as a single oral high dose of 2000 mg/kg b.w.t. in rats. Caution should however be exercised at high doses due to the high elemental content of copper and high possibility of intestinal lining erosion.

A dietary strategy for the management of artemether-lumefantrine-induced cardiovascular and renal toxicity.

BACKGROUND: Unsweetened natural cocoa has antimalarial properties. Unsweetened natural cocoa powder (UNCP), obtained as a result of the removal of cocoa butter from a cocoa bean protects against malaria episodes. Cocoa powder, which is prepared after removal of the cocoa butter, contains about 1.9 % theobromine and 0.21 % caffeine. Concomitant consumption of cocoa and artemether/lumefantrine (A/L) is a common practice in Ghana, West Africa. This study seeks to determine the elemental composition of UNCP and its protective effect on the heart and kidney against (A/L) administration. METHODS: Energy dispersive x-ray fluorescence spectroscopy was used to detect the quality and quantity of the elemental composition in UNCP. Thereafter, 30 nonmalarious male guinea pigs were divided into five groups of six animals each. One group was administered with 75 mg/kg body weight A/L only and another group distilled water (control group). The rest received 300 mg/kg, 900 mg/kg and 1500 mg/kg body weight UNCP for 14 days orally and A/L for the last 3 days (ie day 11 to day 14). Biochemical and histopathological examinations were carried out after euthanisation of the animals. RESULTS: A total of thirty-eight (38) micro and macro elements were detected with the ED-XRF. Macro elements like sodium (Na), magnesium (Mg), aluminium (Al), phosphorus (P), chlorine (Cl), potassium (K), calcium (Ca), manganese (Mn) and iron (Fe) and micro elements like chromium (Cr), copper (Cu), zinc (Zn), arsenic (As), and lead (Pb) were identified and evaluated. Biochemical analysis revealed increases in HDL levels (p>0.05) while there were decreases in LDL levels (p>0.05), creatine kinase and AST levels (P<0.05) in animals that received UNCP compared to A/L only administered group. Urea levels reduced significantly by 53 % (p<0.05) in group that received 1500 mg/kg UNCP. Histopathological examinations of the heart and kidney buttressed the protective effects of cocoa administration. CONCLUSION: The percentage of recommended daily allowance of UNCP for chromium is 3750 % for men and 5250 % for women while % RDA for copper corresponds to 103.6 % in both sexes. UNCP proved to possess cardioprotective and renoprotective potential during artemether-lumefantrine administration.

Unsweetened Natural Cocoa Powder Has the Potential to Attenuate High Dose Artemether-Lumefantrine-Induced Hepatotoxicity in Non-Malarious Guinea Pigs.

Objective. This study investigated the elemental composition of unsweetened natural cocoa powder (UNCP), its effect on nitric oxide, and its hepatoprotective potential during simultaneous administration with high-dose artemether/lumefantrine (A/L). Method. Macro- and microelements in UNCP were analyzed with EDXRF spectroscopy. Thirty (30) male guinea-pigs were then divided into five groups. For groups 3 (low-dose), 4 (medium-dose), and 5 (high-dose), the animals received oral UNCP prophylactically for 14 days. Group 1 received distilled water (14 days) and group 2 A/L for the last 3 days (days 12 to 14). After euthanisation, biochemical and histopathological examinations were carried out in all groups. Results. Phytochemical analysis of UNCP showed the presence of saponins, flavonoids, tannins, and cardiac glycosides. Thirty-eight (38) macro- and microelements were found. UNCP produced significant decreases in ALT, ALP, GGT, and AST levels. A significant increase in total protein levels was observed during A/L+UNCP administration in comparison to 75 mg/kg A/L group. Histopathological examinations buttressed the protective effects of cocoa administration. UNCP administration increased nitric oxide levels 149.71% (P < 0.05) compared to controls. Conclusion. UNCP increases nitric oxide levels and has hepatoprotective potential during A/L administration. A high level of copper was observed which may be detrimental during high daily consumptions of UNCP.

Antibacterial and antispasmodic activities of a dichloromethane fraction of an ethanol extract of stem bark of Piliostigma reticulatum.

OBJECTIVES: This study presents the antispasmodic and antibacterial properties of an ethanol extract and fractions the of stem bark of Piliostigma reticulatum. MATERIALS AND METHODS: The antispasmodic effects of the extract and its fractions were performed on isolated rabbit duodenum. The antibacterial properties were determined as minimal inhibitory and bactericidal concentration of the extract and fractions of P. reticulatum on susceptible and resistant strains of Escherichia coli, Vibrio cholerae, Staphylococcus aureus, Shigella dysenteriae and Salmonella tiphymurium. RESULTS: The ethanol extract of P. reticulatum and fractions (except for heptane) produced concentration-dependent relaxant effects on isolated duodenum preparations. The IC50 of the extract and dichloromethane, ethyl acetate, butanol and aqueous fractions are 0.88452, 0.2453, 0.2909, 0.3946 and 0.3231 mg/ml respectively. The extract was found to significantly antagonize acetylcholine-induced contraction. The susceptible strains E. coli and V. cholerae were the most inhibited by the dichloromethane fraction at 60 mg/mL, as shown by their diameter of inhibition of 13.2 ± 0.76 and 13.3 ± 0.67 mm respectively. Conversely, the dichloromethane fraction, the most active antibacterial fraction, did not inhibit the resistant strains S. dysenteriae and S. tiphymurium. CONCLUSION: The results showed that P. reticulatum stem bark possesses spasmolytic and antibacterial properties and this may contribute to its traditional medicinal use for the treatment of diarrhea.

Phytotherapy of experimental depression: Kalanchoe integra Var. Crenata (Andr.) Cuf Leaf Extract.

CONTEXT: Kalanchoe sp. have been used since 1921 for central nervous system (CNS) disorders such as psychosis and depression. It is known to possess CNS depressant effects. AIMS: To investigate the antidepressant properties of the aqueous leaf extract of Kalanchoe integra. SETTINGS AND DESIGN: The study was carried out at the Kwame Nkrumah University of Science and Technology between 6 a.m. and 3 p.m. MATERIALS AND METHODS: ICR mice were subjected to the forced swimming test (FST) and tail suspension test (TST) after they had received extract (30-300 mg/kg), fluoxetine (3-30 mg/kg), desipramine (3-30 mg/kg) orally, or water (as vehicle). In a separate experiment, mice were pre-treated with reserpine (1 mg/kg), α-methyl paratyrosine (AMPT; 400 mg/kg), both reserpine (1 mg/kg) and AMPT (200 mg/kg) concomitantly, or p-chlorophenylalanine (pCPA; 200 mg/kg) to ascertain the role of the noradrenergic and serotoninergic systems in the mode of action of the extract. STATISTICAL ANALYSIS USED: Means were analyzed by analysis of variance (ANOVA) followed by Newman-Keuls' post hoc test. P < 0.05 was considered significant. RESULTS: In both FST and TST, the extract induced a decline in immobility, indicative of antidepressant-like effect. This diminution in immobility was reversed by pCPA, but not by reserpine and/or AMPT. The extract increased the swimming and climbing scores in the FST, suggestive of possible interaction with serotoninergic and noradrenergic systems. In the TST, the extract produced increases in both curling and swinging scores, suggestive of opioidergic monoaminergic activity, respectively. CONCLUSIONS: The present study has demonstrated the antidepressant potential of the aqueous leaf extract of K. integra is mediated possibly by a complex interplay between serotoninergic, opioidergic, and noradrenergic systems.

Toxicological assessment of polyhexamethylene biguanide for water treatment.

Polyhexamethylene biguanide (PHMB) is an antiseptic with antiviral and antibacterial properties used in a variety of products including wound care dressings, contact lens cleaning solutions, perioperative cleansing products, and swimming pool cleaners. There are regulatory concerns with regard to its safety in humans for water treatment. We decided to assess the safety of this chemical in Sprague-Dawley rats. PHMB was administered in a single dose by gavage via a stomach tube as per the manufacturer's instruction within a dose range of 2 mg/kg to 40 mg/kg. Subchronic toxicity studies were also conducted at doses of 2 mg/kg, 8 mg/kg and 32 mg/kg body weight and hematological, biochemical and histopathological findings of the major organs were assessed. Administration of a dose of 25.6 mg/kg, i.e. 1.6 mL of 0.4% PHMB solution (equivalent to 6.4x10(3) mg/L of 0.1% solution) resulted in 50% mortality. Histopathological analysis in the acute toxicity studies showed that no histopathological lesions were observed in the heart and kidney samples but 30% of the animals had mild hydropic changes in zone 1 of their liver samples, while at a dosage of 32 mg/kg in the subchronic toxicity studies, 50% of the animals showed either mild hepatocyte cytolysis with or without lymphocyte infiltration and feathery degeneration. Lymphocyte infiltration was, for the first time, observed in one heart sample, whereas one kidney sample showed mild tubular damage. The acute studies showed that the median lethal dose (LD50) is 25.6 mg/kg (LC50 of 1.6 mL of 0.4% PHMB. Subchronic toxicological studies also revealed few deleterious effects on the internal organs examined, as seen from the results of the biochemical parameters evaluated. These results have implications for the use of PHMB to make water potable.

A preliminary safety evaluation of polyhexamethylene guanidine hydrochloride.

Polyhexamethylene guanidine hydrochloride (PHMGH) is used worldwide as an antimicrobial agent with broad spectra of activity and also for treating pool water. This non-GLP preliminary study aims at investigating in a subchronic toxicity study possible effects at supra-optimal doses of this biocide. Both acute and subchronic toxicity studies were conducted. LD(50) for PHMGH was estimated to be 600 mg/kg (ie LC(50) 2 ml of 7.5% solution) when administered as a single dose by gavage via a stomach tube in accordance with the expected route of administration. The acute studies showed that the median lethal dose (LD(50)) of 600 mg/kg was accompanied by signs of neurotoxicity. Haematological and biochemical parameters of subchronic toxicity studies were non-significant. Subchronic doses of 0.006 mg/kg, 0.012 mg/kg and 0.036 mg/kg were administered. 20% of the animals at a dose of 0.006 mg/kg and 0.036 mg/kg showed mild degrees of hydropic changes in proximal tubules while 10% of animals at all the doses had their liver tissues showing local areas of mild pericentral hepatocytes degeneration. PHMGH did not produce any major organ defect with regard to the kidney, heart, and liver. The LD(50) was much higher than the recommended dosage by a factor of about 50,000. The recommended residual concentration is far less than the median lethal dose using rats as test subjects. These results could serve as a basis for investigating the full toxicological profile if it is to be used for the treatment of raw water to make it potable.