Genetic and epigenetic modulations in toxicity: The two-sided roles of heavy metals and polycyclic aromatic hydrocarbons from the environment.

This study emphasizes the importance of considering the metabolic and toxicity mechanisms of environmental concern chemicals in real-life exposure scenarios. Furthermore, environmental chemicals may require metabolic activation to become toxic, and competition for binding sites on receptors can affect the severity of toxicity. The multicomplex process of chemical toxicity is reflected in the activation of multiple pathways during toxicity of which AhR activation is major. Real-life exposure to a mixture of concern chemicals is common, and the composition of these chemicals determines the severity of toxicity. Nutritional essential elements can mitigate the toxicity of toxic heavy metals, while the types and ratio of composition of PAH can either increase or decrease toxicity. The epigenetic mechanisms of heavy metals and PAH toxicity involves either down-regulation or up-regulation of some non-coding RNAs (ncRNAs) whereas specific small RNAs (sRNAs) may have dual role depending on the tissue and circumstance of expression. Similarly, decrease DNA methylation and histone modification are major players in heavy metals and PAH mediated toxicity and FLT1 hypermethylation is a major process in PAH induced carcinogenesis. Overall, this review provides the understanding of the metabolism of environmental concern chemicals, emphasizing the importance of considering mixed compositions and real-life exposure scenarios in assessing their potential effects on human health and diseases development as well as the dual mechanism of toxicity via genetic or epigenetic axis.

Low Dose of Nickel and Benzo [a] Anthracene in Rat-Diet, Induce Apoptosis, Fibrosis, and Initiate Carcinogenesis in Liver via NF-Æ˜ß Pathway.

Environmental contaminants such as polycyclic aromatic hydrocarbon (PAH) and heavy metals are major contaminants of food such as fish thus serving as source of exposure to human. This study was designed to evaluate the carcinogenic risk and other risks associated with long-term consumption of environmentally relevant dose of nickel and benzo [a] anthracene in rats. Thirty-six (36) male rats weighing between 80 and 100 g were assigned into 6 groups of 6 animals each; normal, nickel-, and benzo [a] anthracene-exposed groups for 12 and 24 weeks, respectively. Micronucleus and comet analyses were done in the blood, liver, and bone marrow. Liver function, redox, and inflammatory markers (AST, ALT, GGT, SOD, GSH, MDA, protein carbonyl, protein thiol, total protein, IL-10, 1L-1ß, TNF-α, TGF-ß NF-Ƙß, and 8-oxodeoxyguansine) were analysed by standard methods. Immuno-histochemical quantification of Bax, Bcl2, and Erk 1/2 as well as mRNA expression of cyclin D1 was done in liver. From the results, weight gain was observed in varying degrees throughout the exposure period. The polychromatic erythrocytes/normochromatic erythrocytes ratio > 0.2 indicates no cytotoxic effects on the bone marrow. Percentage-MnPCE in blood significantly (p < 0.05) increased throughout exposure duration. Percentage tail DNA in blood was significantly (< 0.05) increased at weeks 20 and 24 in the exposed groups and in liver at weeks 12 (16.22 ± 0.47) and 24 (17.00 ± 0.36) of nickel-exposed rats. The aspartate amino transferase (AST):alanine amino transferase (ALT) ratio indicated fatty liver disease in the benzo [a] anthracene (0.90) and acute liver injury in the nickel (> 10 times greater than the upper limits of the reference group) exposed groups during the first 12 weeks. Observation from the histological and cytological data of the liver revealed the presence of inflammation, fibrosis, and high nuclear/cytoplasmic ratio, respectively, in the nickel and benzo [a] anthracene groups. Only benzo [a] anthracene induced liver oxidative stress with significant (p < 0.05) decrease in SOD (0.64 ± 0.02) activity and increase in protein carbonyl (7.60 ± 0.80 × 10-5) and MDA (57.10 ± 6.64) concentration after 24 weeks. Benzo [a] anthracene up-regulated the cyclin D1 expression and significantly (p < 0.05) increased the levels of the cytokines. Nickel and benzo [a] anthracene significantly (p < 0.05) increased the Bax (183.45 ± 6.50 and 199.76 ± 10.04) and Erk 1/2 (108.25 ± 6.41 and 136.74 ± 4.22) levels when compared with the control (37.43 ± 22.22 and 60.37 ± 17.86), respectively. Overall result showed that the toxic effects of nickel and benzo [a] anthracene might involve fibrosis, cirrhosis, apoptosis, and inflammation of the liver. As clearly demonstrated in this study, benzo [a] anthracene after the 24 weeks of exposure stimulates carcinogenic process by suppressing the liver antioxidant capacity, altering apoptotic, cell proliferation, and differentiation pathways.

Evaluation of long-term effects of nickel and benzo [a] anthracene contaminated diets in rats' kidney; mimicking human exposure from food.

OBJECTIVES: Accumulative effects of heavy metals and polycyclic aromatic hydrocarbon could result in various toxicities. This study evaluated the effects of long-term exposure to low doses of nickel and benzo [a] anthracene on the kidney of rats, simulating human exposure through food. METHODS: Thirty-six (36) Male rats weighing between 80-100 g were assigned into six groups of 6 animals each; Group A (normal), Group B1 and B2 (fed nickel contaminated feed for 12 and 24 weeks), Group C1 and C2 (fed benzo [a] anthracene contaminated feed for 12 and 24 weeks). Blood and kidney of the rats were harvested after animal sacrifice. Serum creatinine and urea concentration and renal Superoxide Dismutase (SOD) activity, GSH, MDA, protein carbonyl, and total protein concentration by spectrophotometric methods. While the concentration of 8-oxodeoxyguanosine in kidney was determined by ELISA method and protein carbonyl by colorimetric method. Renal histological analysis was done with H and E staining. Statistical analysis was performed with Statistical Package for Social Sciences (SPSS) and statistical significance was accepted 95 percent confidence level. RESULT: From the results, urea concentration increased significantly (P<0.05) in the nickel exposed group after 24 weeks exposure whereas creatinine concentration increased significantly (P<0.05) after 12 weeks of exposure when compared with the control. Comparison of the serum urea and creatinine level of the benzo [a] anthracene exposed group with the control showed no significant (P>0.05) difference. Histological observations indicate glomerular atrophy and widened capsular space haemorrhagic areas, visceral and parietal layer of the Bowman's capsule, the proximal convoluted tubule in the nickel exposed group while the kidney of benzo (a) anthracene exposed rats showed deviation in the histo-architecture of the renal parenchyma as evidenced by glomerular atrophy and widened Bowman's capsular space and focal haemorrhagic areas. Protein thiol level and Superoxide dismutase activity was significantly (P<0.05) depleted in the benzo [a] anthracene exposed groups. The levels of total protein, protein carbonyl, and 8-oxodeoxyguanosine were significantly (P<0.05) elevated in the nickel and benzo [a] anthracene exposed groups. CONCLUSION: This study demonstrated the oxidative stress causing effects of benzo [a] anthracene and nickel in the kidney. It also shows that consistent exposure to low doses of the contaminants for a lifetime might result in renal oxidative stress with consequential loss of renal function.

Ginger mitigated the health risks associated with arsenic-contamination of rats feed via inflammatory and apoptosis regulation.

Millions of people around the world are inadvertently exposed to arsenic through drinking water and food. However, food spices possess antioxidants and anti-inflammatory potentials. Therefore, this study evaluated the protective potentials of Zingiber officinale (ginger) against the toxic effects of arsenic in male Wistar rats. Thirty-six Wistar rats were assigned into 6 groups (n = 6); group A1 and A2 (control), group B1 and B2 were fed with arsenic-contaminated feed (3.45x10-3 mg/kg), group C1 and C2 were feed with arsenic-contaminated feed (3.45x10-3 mg) supplemented with ginger respectively for 12 and 24 weeks. The blood, bone marrow, and liver of rats were harvested and prepared for various analyses. Micronucleus and Comet analysis were performed for the genotoxicity assessment every 4 weeks. Activities of AST, ALT, GGT, and SOD, and the concentration of GSH, MDA, protein carbonyl, protein thiol, and total protein, were measured by spectrophotometric methods. Quantification of IL-10, 1 L-1ß, TNF-α, TGF-ß NF-Ƙß, and 8-oxodeoxyguanosine was done by ELISA method while Bax, Bcl2, and Erk 1/2 were quantified by immuno-histochemical staining. mRNA expression of cyclin D1 was quantified using qRT-PCR. Statistical analysis was performed with SPSS and statistical significance was accepted when p<0.05. Result showed significant (p<0.05) decrease in the haemoglobin concentration, red blood cell, lymphocyte counts, tail DNA and MnPCE of rats fed arsenic-contaminated feed compared with control. The supplementation with ginger significantly reduced serum activities of AST and GGT (p<0.05). Ginger supplementation also lowered the arsenic indued increases in liver MDA, protein carbonyl and 8-OXdG levels. Ginger restores to near normal the histological changes due to arsenic exposure. In the arsenic-exposed group, liver IL-10, IL-1ß and TNF-α decreased significantly (p<0.05) at week 24 whereas, NF-Æ˜ß and TGF-ß increased significantly (p 0.05) at weeks 12 and 24 and TNF-α, Bcl2 at week 24. mRNA expression of cyclin D1 was significantly (p<0.05) downregulated in the arsenic and ginger-supplemented groups. This study showed that long-term consumption of arsenic resulted in immunosuppression, anaemia and activated anti-apoptotic process that was mitigated due to ginger supplementation.

Heavy metal concentrations in four fish species from the Lagos lagoon and their human health implications.

Background: Lagos lagoon is constantly being polluted from industrial and human activities. Fishes from Lagos lagoon contribute significant percentages of fish consumption in the Lagos metropolises. Therefore, this study evaluated heavy metal concentrations in tissues of four fish species (Sarotherodon melanotheron, Chrysichthys nigrodigitatus, C. gariepinus, and Ethmalosa fimbriata) from Lagos lagoons and their human health implication. Concentrations of heavy metals and potential health hazard to consumers were evaluated with reference to Estimated Daily Intake (EDI), Target Hazard Quotient (THQ) and Cancer Risk (CR). Results: Concentration of the heavy metals in the fish tissues was below the maximum permissible limit in fish. Similarly, the. EDI of the heavy metals in all the tissues was below the recommended allowance whereas, the. THQ estimated for the heavy metals in the tissues of the fish were less than 1. Consumption of arsenic, nickel, and cadmium in the fish might however pose carcinogenic risk. Conclusions: Although, the measured heavy metal concentration were within permissible limits for human consumption, the calculated health risk values indicated that Arsenic, cadmium and nickel might pose significant health risks to consumers. Therefore, biomonitoring of heavy metal accumulation in tissues of fishes must be put into consideration by regulatory authority.

Polycyclic aromatic hydrocarbons distribution in fish tissues and human health risk assessment on consumption of four fish species collected from Lagos Lagoon, Nigeria.

Lagos Lagoon is a very popular lagoon in Lagos state that receives effluents from neighboring industries. These effluents tend to increase the level of contaminants in the lagoon, thereby creating more stressors for aquatic animals. Determination of polycyclic aromatic hydrocarbons (PAHs) in four commonly consumed fish species from the lagoon and the prediction of possible health risks associated with their consumption were performed in this study. Various levels of PAH were detected in the fish tissues with the highest total concentration of PAH in Sarothoredon melanotheron. High concentrations of benzo(a)pyrene were noticed in Sarothoredon melanotheron and Ethmalosa fimbriata, and their values were above the guideline value of 0.002 µg/g. The dietary daily intake (DDI) value in S. melanotheron 82.00 ×10-5 µg/g/day was highest. Carcinogenic toxic equivalents (TEQ) showed that consumption of S. melanotheron had higher potential to pose carcinogenic risks, while the excess cancer risk (ECR) index for the PAHs in all the assessed fish species was beyond threshold values indicating potential carcinogenic risk from their consumption. No significant association was found between the concentration of PAHs and the size of the fish. Target hazard quotient (THQ) results suggested absence of potential non-carcinogenic risk if individual PAH in the fish are consumed frequently. The study however established possible carcinogenic human health risk from consumption of the fish obtained from Lagos Lagoon. The study recommends monitoring of contamination and consumption of fish from harvest sites within the study region.

Potential inhibitory properties of structurally modified quercetin/isohamnetin glucosides against SARS-CoV-2 Mpro; molecular docking and dynamics simulation strategies.

Concerned organizations and individuals are fully engaged in seeking appropriate measures towards managing Severe Acute Respiratory Syndrome Coronavirus 2 (SAR-CoV-2) infection because of the unprecedented economic and health impact. SAR-CoV-2 Main protease (SARS-CoV-2 Mpro) is unique to the survival and viability of the virus. Therefore, inhibition of Mpro can block the viral propagation. Thirty (30) derivatives were built by changing the glucosides in the Meta and para position of quercetin and isohamnetin. Molecular docking analysis was used for the screening of the compounds. Dynamics simulation was performed to assess the stability of the best pose docked complex. Molecular mechanics binding free energy calculation was done by Molecular Mechanics/Poisson-Boltzmann Surface Area (MMPBSA). Overall analysis showed that the compounds are allosteric inhibitors of SARS-CoV-2 Mpro. Dynamic simulation analysis established the stability of Mpro-ISM-1, Mpro-ISD-3, Mpro-IST-2, Mpro-QM-2, and Mpro-QD-6 complexes with a maximum of 7 hydrogen bonds involved in their interaction. The MMPBSA binding free energies for ISM-1, ISD-3, IST-2, QM-2, and QD-6 were -92.47 ± 9.06, -222.27 ± 32.5, 180.72 ± 47.92, 156.46 ± 49.88 and -93.52 ± 48.75 kcal/mol respectively. All the compounds showed good pharmacokinetic properties, while only ISM-1 inhibits hERG and might be cardio-toxic. Observations in this study established that the glucoside position indeed influenced the affinity for SARS-CoV-2 Mpro. The study also suggested the potentials of ISD-3, QM-2 and QD-6 as potent inhibitors of the main protease, further experimental and clinical studies are however necessary to validate and establish the need for further drug development processes. Therefore, future studies will be on the chemical synthesis of the compounds and investigation of the in-vitro inhibition of SARS-CoV-2.

Health risk assessment and heavy metal accumulation in fish species (Clarias gariepinus and Sarotherodon melanotheron) from industrially polluted Ogun and Eleyele Rivers, Nigeria.

Ogun and Eleyele Rivers are in the Western part of Nigeria with a potential risk of heavy metal pollution because of many industrial wastes channeling through their courses. Therefore, in this study, the concentration of heavy metals and the possible human health risk of consuming Clarias gariepinus and Sarotherodon melanotheron collected from industrially polluted Ogun and Eleyele Rivers in Nigeria were evaluated. The concentration of arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), manganese (Mn), nickel (Ni), and lead (Pb) in tissues (gill, muscle, and liver) of fish was measured using Atomic Absorption Spectroscopy (AAS) and compared with the maximum permissible. The Estimated Daily Intake (EDI), Targeted Hazard Quotient (THQ), and Carcinogenic Risk (CR) of the metals were estimated for the determination of human health risk. Probabilistic predictions of the health risk were performed with Oracle Crystal Ball software. Results of this study showed that the dry weight concentrations of the metals in the gills, liver, and muscle of the two fish species from the two sites were well below the permissible limits set by the joint FAO/WHO Expert Committee. Only the EDI for arsenic in gills of C. gariepinus obtained from the Ogun River exceeded the set limit. The THQ was >1 for As in the gills and liver of C. gariepinus and S. melanotheron obtained from the Ogun river suggesting non-carcinogenic risk to the consumers. The carcinogenic risk above 10-6 obtained for As, Cd, and Ni in the tissues of the two fish species suggested cancer risk to the consumers of fish from the two rivers. Consequent to our observation, consumption of fish from the study site presents some public health concerns. Therefore, this study advises routine heavy metal monitoring of fish along these rivers to implement regulatory standards by the government environmental health management agencies.

Effect of Methanolic Leaf Extract of Talinum triangulare (Jacq). Willd. on Biochemical Parameters in Diet induced Dyslipidemia Wistar Rats.

OBJECTIVE: To investigate the effect of methanolic leaf extract of Talinum triangulare on hematological parameters, enzymatic and non-enzymatic antioxidant status, and serum lipid in Wistar rats fed standard laboratory, or 2% cholesterol-enrich diet. MATERIAL AND METHODS: Wistar rats (180-210g) divided into six groups of six animals (males) each were fed 2% cholesterol-enriched diet and orally treated with 0.9% saline or extract of Talinum triangulare (250, 500, and 1000 mg/kg per body weight) daily for eight weeks. Lipid profile, lipid peroxidation (MDA), hematological parameters, and their functional indices and serum antioxidant enzymes (catalase, glutathione -S-transferase, and superoxide dismutase) activities and glutathione status were assessed in normal and diet-induced hypercholesterolemic extract treated rats and compared with the rats treated with 100 mg/kg per bwt standard drug gemfibrozil. RESULTS: A significant (P < 0.05) increase in lipid profile (total glyceride, total cholestrol, low-density lipoprotein, and very low-density lipoprotein), MDA and reduction (P < 0.05) in enzymatic and nonenzymatic antioxidant status coupled with alterations in hematological parameters was observed in the serum of hypercholesterolemic rats when compared with animals on a normal diet. Coadministration of methanolic leaf extracts of Talinum triangulare or gemfibrozil significantly (P < 0.05) restored the elevated serum lipid profile, MDA, and the deranged hematological parameters to near normal. The extract also protected against hypercholesterolemic-induced diminished enzymatic and nonenzymatic antioxidant status. The activities of the plant extract are dose (250, 500, and 1000 mg/kg) dependent and it compared favorably with the standard drug gemfibrozil. CONCLUSION: The present study suggested that the extract of Talinum triangulare might protect against hypercholesterolemic-induced altered lipid profiles, oxidative stress, and also improve the status of antioxidant defense system and hematopoiesis. SUMMARY: Elevated lipid profile (total glyceride, total cholestrol, low-density lipoprotein, and very low-density lipoprotein), lipid peroxidation (MDA), and reduced enzymatic and nonenzymatic antioxidant status coupled with alterations in hematological parameters was observed in the serum of hypercholesterolemic rats when compared with animals on a normal dietCoadministration of methanolic leaf extracts of Talinum triangulare significantly (P < 0.05) restored the elevated serum lipid profile, MDA, and the deranged hematological parameters to near normal.The extract also protected against hypercholesterolemic-induced diminished enzymatic and bnonenzymatic antioxidant status.The activities of the plant extract was dose-dependent and it compared favorably with the standard drug gemfibrozil. Abbreviations used: Lipid peroxidation (MDA), (catalase (CAT), glutathione-S-transferase (GST), superoxide dismutase (SOD), glutathione (GSH), Thrombocytes indices (PLT), Red blood cell (RBC), Packed cell volume (PVC), Mean corpuscular hemoglobin(MCH), Mean corpuscular hemoglobin concentration (MCHC), Total glyceride (TG), Very low density lipoprotein (VLDL), Total cholesterol (TC), Low density lipoprotein (LDL), High density lipoprotein (HDL) and 3-Hydroxy-3-methyl-glutaryl-CoA reductase(HMG-CoA).

Inhibition of In Vivo Growth of Plasmodium berghei by Launaea taraxacifolia and Amaranthus viridis in Mice.

Launaea taraxacifolia and Amaranthus viridis used by people of Western Africa in the treatment of malaria and related symptoms were assessed for their antiplasmodial value against the chloroquine sensitive strain of Plasmodium berghei. Crude extracts (200 mg/kg) and chloroquine (5 mg/kg) were administered to different groups of Swiss mice. The percentage of parasitemia, survival time, and haematological parameters were determined. Both extracts significantly (p < 0.05) inhibited parasitemia and improved survival time in infected mice. The crude extracts prevented loss of some haematological parameters. A. viridis had a distinct effect on the packed cell volume. The extract was able to protect the liver from some of the damage. This study however showed that the methanolic extracts of A. viridis and L. taraxacifolia possess antiplasmodial activity. The results of this study can be used as a basis for further phytochemical investigations in the search for new and locally affordable antimalarial agents.

Sub-chronic Administration of Methanolic Whole Fruit Extract of Lagenaria breviflora (Benth.) Roberty Induces Mild Toxicity in Rats.

BACKGROUND: The effect of the methanolic whole fruit extract from Lagenaria breviflora on vital organs and antioxidant enzymes was investigated in this study. MATERIALS AND METHODS: L. breviflora (250, 500 and 1000 mg/kg/b.w.t./day/rat) was fed orally with the cannula to male albino rats for 28 days. At the end of the treatment, the rats were sacrificed and the effect of the extract on histology of the liver, heart, lipid peroxidation, tissue and serum antioxidant enzymes (superoxide dismutase, catalase, glutathione-s-transferase, glutathione peroxidase) activities, glutathione, myocardial marker enzymes (creatine kinase [CK], lactate dehydrogenase [LDH], alanine transaminase [ALT], and aspartate transaminase [AST]) in serum, and heart homogenate were assessed. RESULTS: The extract demonstrated mild organ doses dependent (500 and 1000 mg/kg) pathological alterations in the architectural section of the liver and heart. At 250 mg/kg/b.w.t., the extract caused a significant (P < 0.05) increase in the level of thiobarbituric reacting acids substance and antioxidant enzyme activities, but causes (P < 0.05) decrease in serum and tissue antioxidant capacity at 500 and 1000 mg/kg/b.w.t., respectively. Also on these two doses, a significant (P < 0.05) increase in serum activity of CK, LDH, ALT, and AST and concomitantly decrease (P < 0.05) in heart homogenate were also observed. CONCLUSION: The results suggested that the Fruit of L. breviflora may contain phytotoxic Substances(s) which may be hepatotoxic, cardiotoxic or able to induce oxidative stress at high concentration. Hence, the consumption of the plant should be taken with caution. SUMMARY: Methanolic whole fruit extract from Lagenaria breviflora demonstrate dose dependent mild toxicity on vital organs (Heart and liver) and anti-oxidant enzymes. The fruit of Lagenaria breviflora may contain Phyto-toxic substance (s) which may be hepatotoxic, Cardio-toxic or able to induce oxidative stress at high concentration. Hence, the consumption of the plant should be taken with caution.

Hepatoprotective Potential of Some Local Medicinal Plants against 2-Acetylaminoflourene-Induced Damage in Rat.

The in vivo micronucleus assay was used to examine the anticlastogenic effects of crude extracts of Bridelia ferruginea, Vernonia amygdalina, Tridax procumbens, Ocimum gratissimum, and Lawsonia inermis in Wistar albino rats. Extracts of doses of 100 mg/kg body weight were given to rats in five groups for seven consecutive days followed by a single dose of 2-AAF (0.5 mmol/kg body weight). The rats were sacrificed after 24 hours and their bone marrow smears were prepared on glass slides stained with Giemsa. The micronucleated polychromatic erythrocyte cells (mPCEs) were thereafter recorded. The hepatoprotective effects of the plant extracts against 2-AAF-induced liver toxicity in rats were evaluated by monitoring the levels of alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and histopathological analysis. The results of the 2-AAF-induced liver toxicity experiments showed that rats treated with the plant extracts (100 mg/kg) showed a significant decrease in mPCEs as compared with the positive control. The rats treated with the plant extracts did not show any significant change in the concentration of ALP and GGT in comparison with the negative control group whereas the 2-AAF group showed a significant increase (P < 0.05) in these parameters. Some of the leaf extracts also showed protective effects against histopathological alterations. This study suggests that the leaf extracts have hepatoprotective potential, thereby justifying their ethnopharmacological uses.

Protective effects of Vernonia amygdalina against sodium arsenite-induced genotoxicity in rat.

OBJECTIVES: Contamination of the environment with arsenic (As) from both human and natural sources is known as a global problem. This study investigated the chemoprotective potential of Vernonia amygdalina leave extract against sodium arsenite-induced genotoxicity and hepatotoxicity. MATERIALS AND METHODS: Genotoxic effects were evaluated in the rat bone marrow using micronuclei. The gamma glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) activities were assayed in rat serum. RESULTS: Pre-treatment with extract of V. amygdalina at doses 5 mg/kg and 10 mg/kg significantly decreased the frequency of micronucleated polychromatic erythrocytes (PCEs). The GGT and ALP activities were elevated more than fourfold, in the liver of rats treated with sodium arsenite, while it was reduced almost to half when the sodium arsenit-treated rats were fed fresh V. amgdalina leave extracts The phytochemical constituents of V. amygdalina assayed in this study may be responsible for high radical scavenging of the DPPH free radical observed. CONCLUSION: The present results indicate that V. amygdalina extract is capable of suppressing the chromosomal aberration induced by sodium arsenite in rat. Thus, V. amygdalina may be a potent chemoprotective agent against the toxicity of sodium arsenite in rats.

Antibacterial activity and in vitro cytotoxicity of extracts and fractions of Parkia biglobosa (Jacq.) Benth. stem bark and Ageratum conyzoides Linn. leaves.

Many species of plants in African countries are widely used in the rural communities where there is little or no access to modern medicine. However, the safety and effectiveness of these medicinal plants are poorly evaluated. The stem bark of Parkia biglobosa Jacq. and leaves of Ageratum conyzoides Linn. were investigated for their antibacterial and cytotoxic activities. The plant materials were extracted with 95% ethanol, and fractionated with petroleum ether, chloroform and ethyl acetate. The antibacterial effects of the extracts and fractions of the plant materials were assayed on the bacterial cultures of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin Resistant Staphylococcus aureus (MRSA) and Clostridium perfringes. Ethanol extracts of P. biglobosa and A. conyzoides were screened for cytotoxicity using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. Two cancer cell lines (SK-MES 1 and SK-LU 1) and one normal cell line (human skin fibroblast cell line, FS5) were used for the screening of the extracts and the fractions obtained. The ethanolic extracts and fractions of P. biglobosa and A. conyzoides showed the best activity against E. coli, S. aureus and MRSA. All fractions of A. conyzoides leaves have no activity against P. aeruginosa. Human lung cancer cell lines (SK-LU 1 and SK-MES 1) and human skin fibroblast cell line (FS5 cells) were treated with various concentrations (3.9µg/ml-2mg/ml) of the extracts and fractions for 24h. SK-MES 1 cells are more susceptible to treatment with the plant fractions. All the fractions of A. conyzoides leaves and the petroleum ether fraction of P. biglobosa were cytotoxic to SK-MES 1 cells, which to some extent may support their traditional inclusion in herbal preparations for treatment of cancer. The overall results provided evidence that the studied plant extracts might be potential sources of new antibacterial and anticancer drug.

Ethnopharmacological survey and in vitro evaluation of wound-healing plants used in South-western Nigeria.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional healers in Nigeria employ a range of plant preparations as wound healing agents. Despite the use of local plants in wound healing, there is only scant literature on the wound healing properties of these plants to support the continued therapeutic application of these herbal remedies. AIM OF THE STUDY: To document plants commonly used to treat wounds in South-western Nigeria and to test the scientific basis of such claims using relevant in vitro tests. MATERIALS AND METHODS: Structured questionnaires were used to determine which plant preparations are in common use, via interviews with Yoruba traditional healers. Aqueous and ethanolic extracts of the nine most common plants cited by the healers were collected, identified and tested using relevant in vitro wound healing assays. Minimum inhibitory concentrations (MIC) were determined against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis. Antioxidant activity was measured by DPPH assay and fibroblast proliferation determined by neutral red assay. RESULTS: A total of 20 traditional healers from South-western Nigeria were involved in the study. Thirty-six plant species were recorded with their local names and parts used in the traditional wound healing preparations. Ethanolic extracts of nine species most frequently cited by the healers exhibited strong antioxidant activities (3.8-31.3 µg/ml) comparable to ascorbic acid (7.3 µg/ml). Crude extracts of the selected plants also inhibited the growth of bacteria with MIC values 0.3-7.6 mg/ml. Ethanol extracts of Bridelia ferruginea Benth. (1-30 µg/ml) and Parkia biglobosa Jacq. (15-30 µg/ml) influenced the proliferation of dermal fibroblasts significantly (p<0.05). Extracts from the remaining seven plants either had no effect on fibroblast proliferation or were cytotoxic. CONCLUSION: Traditional use of many wound-healing plants from Nigeria can be rationalised by activity determined in relevant in vitro investigations of ethanol and aqueous extracts. These results support the traditional selection of these plants in South-western Nigeria for wound healing.

Antibacterial, antioxidant and fibroblast growth stimulation activity of crude extracts of Bridelia ferruginea leaf, a wound-healing plant of Nigeria.

AIM OF THE STUDY: Determination of pharmacological activity relevant to wound healing of Bridelia ferruginea leaf, a traditional medicine used to treat wounds in rural Nigeria. MATERIALS AND METHODS: Aqueous and ethanolic leaf extracts were tested against bacterial species of relevance to wound infections: Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa. The ethanolic extracts were assessed for their ability to stimulate the growth of human dermal fibroblasts (FS5) and protect against damage induced by hydrogen peroxide. Antioxidant activity was also assessed using the DPPH assay. RESULTS: Both aqueous and ethanolic extracts had weak antibacterial activity (MIC>470 µg/ml). A significant effect (p<0.001) on the growth of FS5 fibroblasts was observed only at a concentration of 5 µg/ml (28% increase), above which the extracts appeared toxic to the cells. The ethanolic extract offered the highest protection against H(2)O(2) damage to FS5 cells, comparable with catalase (82% at 250 µg/ml). The DPPH assay revealed antioxidant activity of the ethanolic leaf extract with IC(50) 12.5±0.3 µg/ml comparable to l-ascorbic acid (7.3±0.1 µg/ml). CONCLUSION: The antibacterial, modest fibroblast stimulation activity and relatively strong antioxidant activity lend some support to the topical use of Bridelia ferruginea leaf for wound-healing in the traditional medicine of South-western Nigeria.