Michael A. Gbadegesin

In vitro free radical scavenging and antioxidant properties of ethanol extract of Terminalia glaucescens.

Background: Reactive oxygen species (ROS) are implicated in various pathological conditions. Synthetic antioxidants have adverse health effects, while many medicinal plants have antioxidant components that can prevent the harmful effects of ROS. Objectives: This study quantitatively determined the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant properties of ethanol extract of the stem bark of Terminalia glaucescens (EESTG). Materials and Methods: The objectives were achieved based on in vitro assays. Data were analyzed by Sigma Plot (version 11.0). Results: Using gallic acid as the standard compound, TPC value obtained was 596.57 μg GAE/mg extract. TFC content of EESTG, determined as quercetin equivalent was 129.58 μg QE/mg extract. Furthermore, EESTG significantly (P < 0.001) displayed higher reducing power activity than the standard compounds (ascorbic acid and butylated hydroxytoluene [BHT]). Total antioxidant capacity assay, measured by phosphomolybdate method, was 358.33 ± 5.77 μg butylated hydroxytoluene equivalents [BHTE]/mg extract. β-carotene-linoleate bleaching method affirmed the potency of EESTG because of its significantly (P < 0.001) higher anti-oxidant activity when compared with quercetin and BHT. Based on DPPH assay, EESTG displayed significantly (P < 0.001) higher activity than BHT, while the hydroxyl radical scavenging activities of BHT and quercetin significantly (P < 0.001) exceeded that of the extract, although EESTG still displayed a high level of activity obtained as 83.77% in comparison to 92.80% of the standard compounds. Conclusion: Findings from this study indicate the presence of promisingly potent phytoconstituents in EESTG that have the capability to act as antioxidants and free radical scavengers.

Comparative hepatotoxicity and clastogenicity of sodium arsenite and three petroleum products in experimental Swiss Albino Mice: the modulatory effects of Aloe vera gel.

Petroleum products (PPs) consist of complex chemical mixtures, mainly hydrocarbons. Their composition varies considerably with source and use. Inappropriate manual handling and use of PPs, in countries like Nigeria, results in excessive skin contact with the possibility of hazard to health. There has been inadequate evidence to classify diesel, kerosene and hydraulic oil as human carcinogens and there is limited evidence for their toxicity and carcinogenicity in experimental animals. We compared the hepatotoxicity and clastogenicity of diesel, petrol or hydraulic oil with that of sodium arsenite (Na(2)AsO(2)) in mice. Our findings showed that these PPs are capable of inducing gamma-glutamyl transferase (gammaGT) activity in the serum and liver to levels comparable with that induced by Na(2)AsO(2). Mice treated with individual PPs have elevated mean liver and serum gammaGT at levels that are significantly different from the values observed for the negative control group. Also, the individual PPs alone have micronuclei formation induction activity similar to Na(2)AsO(2). We found that treatment with Aloe vera gel before the PPs significantly reduced mean liver and serum gammaGT, and the mean number of micronuclei scored when compared with groups administered each of the PPs alone, supporting the presence of hepatoprotective components in Aloe vera.

Modulatory role of Acacia honey from north-west Nigeria on sodium arsenite-induced clastogenicity and oxidative stress in male Wistar rats

Effect of Acacia honey from north-west Nigeria on sodium arsenite-induced oxidative damage and clastogenicity in male Wistar rats was investigated. Animals were divided into four groups and were treated daily via oral gavage for one week before they were sacrificed. Brain, liver and blood serum were collected for antioxidant and protein assays. Clastogenicity, in vitro antioxidant activity, vitamins and minerals were also evaluated. From the results, co-administration of Acacia honey with sodium arsenite on the animals increased (P < 0.05) glutathione peroxidase, superoxide dismutase and catalase activities with concomitant decrease in malondialdehyde levels and anti-clastogenic effects relative to the group treated with sodium arsenite only. The honey possesses reducing power, high hydrogen peroxide scavenging activity, good amount of vitamins (A, C and E), flavonoids (5.08 ± 0.92 mg QE/100 g) and phenolics (5.40 ± 0.69 mg GAE/100 g). The minerals present include zinc, iron, sodium, magnesium, potassium and calcium. In conclusion, Acacia honey from Nigeria may mitigate oxidative stress and clastogenicity.

Evaluation of hepatotoxicity and clastogenicity of carbofuran in male Wistar rats

Carbofuran based pesticides have gained wide usage in Nigeria recently. Consequently, animals and human populations are exposed to them in the environment. Information on in vivo toxicity of carbofuran in experimental models is scanty. The present study therefore examined the hepatotoxicity and clastogenic effects of carbofuran in rats. Male Wistar rats were exposed to carbofuran (p.o) at 0-5mg/kg bw for 5weeks. Carbofuran induced significant (p<0.05) increase in the serum activity of gamma-glutamyltransferase when compared with the negative control, but not activity of serum alanine and aspartate aminotransferases. It also significantly (p<0.05) induced micronucleated polychromatic erythrocytes formation in the bone marrow as compared with the control. The level of induction is dose dependent in both cases. In addition, there was significant (p<0.05) higher number of hepatic cells in the cell/mm(2) assay for the group treated with carbofuran. Histopathological analysis of liver samples from the treated groups revealed lesions ranging from general congestion (portal, central venous and sinusoidal), mild periportal cellular infiltration, diffused sinusoidal congestion and hepatic necrosis to severe congestion. Findings from this study suggest that carbofuran has clastogenic and hepatotoxic effects in rats. It therefore may constitute an environmental health risks in individuals so exposed.

Toxicity associated with repeated administration of artemether-lumefantrine in rats.

Chemotherapy remains an important approach in the fight against malaria. Artemether–lumefantrine combination is widely in use due to its effectiveness against Plasmodium falciparum. Misuse in the form of multiple repeated doses of this anti‐malaria drug is rampant in Nigeria. This study was designed to assess the hepatotoxic and clastogenic potential of extreme misuse of artemether–lumefantrine in rats. Graded doses of artemether–lumefantrine (1–5 mg/kg body weight) were administered by oral gavage for 6 weeks, twice daily, for 3 consecutive days per week. Artemether–lumefantrine, at all doses, did not have significant effects on the body and relative liver weight of treated group compared to the negative control group. The mean γ‐glutamyltransferase, alanine, and aspartate aminotransaminase activity in groups of artemether–lumefantrine treated rats were significantly higher (p < 0.05) than that of the negative control group indicating that repeated administration of artemether–lumefantrine may be hepatotoxic. Findings from histological analyses of liver cross‐section support the enzyme pattern of hepatoxicity. In addition, the drug, at all experimental doses, significantly induced (p < 0.05) formation of micronucleated polychromatic erythrocytes in the bone marrow cells of the treated rats compared with the negative control indicating clastogenic potential of the drug when misused.

Protective effect of Juglans nigra on sodium arsenite-induced toxicity in rats

Background: Consumption of arsenic contaminated water has been implicated in metalloid-induced carcinogenesis. Dietary intake of certain plant products with chemoprotective properties may protect against the onset of diseases and promote maintenance of health. Objectives: We investigated the outcome of black walnut Juglans nigra (JN) consumption on sodium arsenite (SA)-induced toxicity in rats. Materials and Methods: Wister albino rats were treated as follows: Control, SA only (positive control) (2.5 mg/kg body weight), JN only (100 mg/kg weight), and JN+SA coadministered. After 5 weeks animals were sacrificed whole blood, femur, liver and testis harvested were assessed for hepatic transaminases and clastogenicity. Histology of the liver, sperm morphology and quality were also assessed. Data were analyzed (ANOVA) and expressed as means ±SD. Results: SA treatment elevated hepatic transaminases level in serum (P < 0.05), induced histological changes in liver: fibroplasia and periportal hepatocytes infiltration by mononuclear cells. These changes were ameliorated by JN (P < 0.05) coadministration. SA induced micronuclei formation (P < 0.05). Again JN decreased (P < 0.05) micronuclei formation by 50%. Sperm count and motility decreased (P < 0.05) in all groups compared to control. Conclusion: JN showed no protection against arsenite effect on sperm quality. Hepatoprotective and anticlastogenic effects were apparent suggesting a chemopreventive potential active against arsenite genotoxicity and chromosomal instability which have implication for metalloid-induced carcinogenesis.

In vitro antioxidant/radical scavenging activities and hepatoprotective roles of ethanolic extract of Cassia occidentalis leaves in sodium arsenite-treated male Wistar rats.

Aims: To investigate in vitro antioxidant/radical scavenging activities and hepatoprotective ability of ethanolic leaf extracts of Cassia occidentalis (COLEX) in male Wistar rats treated with sodium arsenite (NaAsO2). Study Design/Methodologies: Using four different methodologies, the anti-oxidant/free radical scavenging activities of COLEX were determined in comparison with standard antioxidants, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). For the hepatoprotection study, four groups of rats were used. Groups A: Control group given distilled water only; B: Given NaAsO2 at 2.5 mg•kg bw/day (p.o.) for 2 weeks; C: Administered COLEX alone at 200 mg•kg bw a day for 2 weeks (p.o.); D: Pre-treated with COLEX for 2 weeks followed by NaAsO2. The activities of the enzymes aspartate and alanine aminotransferases (AST and ALT), alkaline phosphatase (ALP) and γglutamyl transferase (γGT) were determined in the treated and control animals as indices of hepatotoxicity. Place and Duration of the Study: The animal treatment and analyses were carried out at Department of Biochemistry, University of Ibadan between February and June 2008. Research Article British Journal of Medicine & Medical Research, 3(4): 2141-2156, 2013 2142 Results: At 25, 40 and 50 μg•ml concentrations of the extracts or the antioxidants, the reducing power is of the order BHA > BHT > COLEX. At 50 μg•ml, the percentage inhibitions of peroxidation by COLEX, BHA and BHT were respectively 96.2%, 97.3% and 98.4% while percentage DPPH scavenging effect of COLEX, BHA and BHT were 62.5%, 67.5% and 61.3% respectively. The H2O2 scavenging activities were respectively 53.0%, 85.3% and 97.8% for COLEX, BHA and BHT. Pre-treatment with COLEX before administration of NaAsO2 led to significant (p < 0.05) reduction in the mean liver and serum γGT, and serum ALP and AST activities when compared with group administered only NaAsO2. Conclusion: COLEX exhibited hepatoprotective effects against NaAsO2 toxicity in male rats.

Inhibitory Effects of Sodium Arsenite and Acacia Honey on Acetylcholinesterase in Rats

This study was conducted to investigate the effect of sodium arsenite and Acacia honey on acetylcholinesterase (AChE) activity and electrolytes in the brain and serum of Wistar rats. Male Wistar albino rats in four groups of five rats each were treated with distilled water, sodium arsenite (5 mg/kg body weight), Acacia honey (20% v/v), and sodium arsenite and Acacia honey, daily for one week. The sodium arsenite and Acacia honey significantly (P < 0.05) decreased AChE activity in the brain with the combined treatment being more potent. Furthermore, sodium arsenite and Acacia honey significantly (P < 0.05) decreased AChE activity in the serum. Strong correlation was observed between the sodium and calcium ion levels with acetylcholinesterase activity in the brain and serum. The gas chromatography mass spectrometry analysis of Acacia honey revealed the presence of a number of bioactive compounds such as phenolics, sugar derivatives, and fatty acids. These findings suggest that sodium arsenite and/or Acacia honey modulates acetylcholinesterase activities which may be explored in the management of Alzheimers diseases but this might be counteracted by the hepatotoxicity induced by arsenics.

Methanol extract of Adansonia digitata leaf protects against sodium arsenite-induced toxicities in male wistar rats

Background: Human and animal population exposure to arsenic through the consumption of arsenic contaminated water is rampant in many parts of the world. Protective agents of medicinal plants origin could provide maximum protection against toxicities of various kinds. Objective: The protective role of orally administered methanol extract of the leaves of Adansonia digitata (MELAD) on sodium arsenite (SA) - induced clastogenicity and hepatotoxicity in male Wistar rats was evaluated. Materials and Methods: Thirty male Wistar rats divided into six Groups (1–6) of five animals each were used for the study. Group 1 (negative control) received distilled water and normal diet only, Groups 2–6 received the extract (at 250 or 500 mg/kg body weight) and/or SA at 2.5 mg/kg body weight. Results: There was statistically significant (P < 0.05) increase in the number of micronucleated polychromatic erythrocytes and lipid peroxidation in the SA group as compared with the negative control and treated groups. Administration of the extract reduced the effects of SA on the above parameters. Activities of serum alanine and aspartate aminotransferases did not show statistically significant effects; however, the histological analyses revealed periportal cellular infiltration by mononuclear cells, whereas the MELAD treated groups show mild cellular infiltration and mild portal congestion. Conclusions: MELAD protect against SA-induced toxicities in rats, and it may offer protection in circumstances of co-exposure and cases of arsenicosis.

Isoniazid Induced Toxicities and Idiosyncratic Responses in Male Albino Wistar Rats

Isoniazid (INH) is an anti-tuberculosis drug administered over a long period. Upon metabolism in the liver, INH generates nitrogen-centered radicals, reacting with cellular macromolecules, and induces toxic and transformational changes in cells and tissues. Here we examined the side effects of long-term (chronic) administration of isoniazid (2.5 and 5mg/kg) once daily for 30, 60 and 90 days consecutively: on hepatic transaminases, histological changes in hepatocytes and induction of micronuclei in the bone marrow and possible genotoxicity in E. coli PQ37. In addition, blood glucose was monitored during the various treatment period. Biochemical analysis of hepatic transaminases (I³ -glutamyl-, alanine amino-, aspartate aminotransferases and alkaline phosphatase) in INH treated group was significantly (p 0.05) in GST in both treatment groups at day 60. There was also a significant increase ( p <0.05) in the activity of superoxide dismutase activity. Micronucleus analysis further revealed an induction of micronucleated polychromatic erythrocytes (mPCEs), which was significant ( p <0.05) for both treatment doses at days 30, 60 and 90 respectively. In addition, INH genotoxicity assessed by UMU chromotest indicated that the 5mg/kg dosage has an induction ratio above the genotoxicity threshold of 1.5 suggesting genotoxicity in E.coli PQ37. Taken together, INH treatment at both doses (2.5 and 5mg/kg body weight) was hepatotoxic and induced nephrotoxic damages, in addition to mutagenic effect which is more pronounced at 2.5mg/kg dose, thereby suggesting dose-dependent cellular and genetic toxicity.