Ademola Adetokunbo Oyagbemi

Molecular targets of [6]‐gingerol: Its potential roles in cancer chemoprevention

A wide variety of phenolic compounds derived from spices possess potent antioxidant, anti‐inflammatory, antimutagenic, and anticarcinogenic activities. [6]‐gingerol (1‐[4′‐hydroxy‐3′‐methoxyphenyl]‐5‐hydroxy‐3‐decanone) is the major pungent principle of ginger, with numerous pharmacological properties including antioxidant, anti‐inflammation, and antitumor promoting properties. It could decrease inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF‐α) expression through suppression of I‐kappaB alpha (IκBα) phosphorylation, nuclear factor kappa B (NF‐κB) nuclear translocation. Other antiproliferative mechanisms of [6]‐gingerol include the release of Cytochrome c, Caspases activation, and increase in apoptotic protease‐activating factor‐1 (Apaf‐1) as mechanism of apoptosis induction. Taken together, the chemopreventive potentials of [6]‐gingerol present a promising future alternative to therapeutic agents that are expensive, toxic, and might even be carcinogenic.

Lack of reversal of oxidative damage in renal tissues of lead acetate-treated rats

Removal of lead from the environment of man or otherwise, the movement of man from lead‐contaminated areas has been employed as a means of abatement of the toxic effects of lead. Whether toxic effects in already‐exposed individuals subside after lead withdrawal remains unanswered. To understand the reversibility of nephrotoxicity induced by lead acetate, male Wistar rats were orally exposed to 0.25, 0.5, and 1.0 mg/mL of lead acetate for 6 weeks. Activities of glutathione‐s‐transferase, catalase (CAT), superoxide dismutase (SOD) and the concentrations of hydrogen peroxide (H2O2), and malondialdehyde increased significantly (p < 0.05) in a dose‐dependent manner, whereas reduced glutathione (GSH) level and glutathione peroxidase activity were significantly reduced. The pattern of alterations in most of the oxidative stress and antioxidant parameters remained similar in rats from the withdrawal period, although CAT and SOD activities reduced, in contrast to their elevation during the exposure period. Serum creatinine levels were significantly elevated in both exposure and withdrawal experiments whereas serum blood urea nitrogen levels were not significantly different from the control in both exposure and withdrawal periods. The histological damage observed include multifocal areas of inflammation, disseminated tubular necrosis, and fatty infiltration of the kidney tubules both at exposure and withdrawal periods. The results suggest that lead acetate‐induced nephrotoxicity by induction of oxidative stress and disruption of antioxidant. The aforementioned alterations were not reversed in the rats left to recover within the time course of study.

Failure of recovery from lead induced hepatoxicity and disruption of erythrocyte antioxidant defence system in Wistar rats.

Lead acetate (PbA) is one of the major environmental contaminants with grave toxicological consequences both in the developing and developed countries. The liver and erythrocyte antioxidant status and markers of oxidative were assessed. Exposure of rats to PbA led to significant decline (p < 0.05) in hepatic and erythrocyte glutathione peroxidase (GPx), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) content. Similarly, malondialdehyde (MDA) and H(2)O(2) concentrations were significantly (p < 0.05) elevated. Histopathology and immunohistology of liver of rats exposed to PbA showed focal areas of necrosis and COX-2 expression after 6 weeks of PbA withdrawal. Taken together, hepatic and erythrocytes antioxidant defence system failed to recover after withdrawal of the exposed PbA for the period of the study. In conclusion, experimental animals exposed to PbA did not recover from hepatotoxicity and disruption of erythrocyte antioxidant defence system via free radical generation and oxidative stress.

Evaluation of the anti-diabetic properties of Mucuna pruriens seed extract

OBJECTIVE To explore the antidiabetic properties of Mucuna pruriens(M. pruriens). METHODS Diabetes was induced in Wistar rats by single intravenous injection of 120 mg/kg of alloxan monohydrate and different doses of the extract were administered to diabetic rats. The blood glucose level was determined using a glucometer and results were compared with normal and untreated diabetic rats. The acute toxicity was also determined in albino mice. RESULTS Results showed that the administration of 5, 10, 20, 30, 40, 50, and 100 mg/kg of the crude ethanolic extract of M. pruriens seeds to alloxan-induced diabetic rats (plasma glucose > 450 mg/dL) resulted in 18.6%, 24.9%, 30.8%, 41.4%, 49.7%, 53.1% and 55.4% reduction, respectively in blood glucose level of the diabetic rats after 8h of treatment while the administration of glibenclamide (5 mg/kg/day) resulted in 59.7% reduction. Chronic administration of the extract resulted in a significant dose dependent reduction in the blood glucose level (P<0.001). It also showed that the antidiabetic activity of M. pruriens seeds resides in the methanolic and ethanolic fractions of the extract. Acute toxicity studies indicated that the extract was relatively safe at low doses, although some adverse reactions were observed at higher doses (8-32 mg/kg body weight), no death was recorded. Furthermore, oral administration of M. pruriens seed extract also significantly reduced the weight loss associated with diabetes. CONCLUSIONS The study clearly supports the traditional use of M. pruriens for the treatment of diabetes and indicates that the plant could be a good source of potent antidiabetic drug.

Ameliorative effects of Cnidoscolus aconitifolius on anaemia and osmotic fragility induced by proteinenergy malnutrition

This study was designed to evaluate the ameliorative effect of dietary supplementation of Cnidoscolus aconitifolius leaf on anaemia and changes in erythrocyte osmotic fragility in protein energy malnourished rats. Protein energy malnutrition has been associated with anaemia and changes in osmotic fragility, deformability and lifespan of erythrocytes. In this study, protein-energy malnutrition induced in weanling male Wister rats by feeding them low protein diet for 3 weeks was associated with significantly reduced (P (RBC), white blood cell count (WBC), platelet counts and mean corpuscular count (MCV). It was also associated with increased erythrocyte osmotic fragility at 0.5- 0.7% NaCl concentration. Upon introduction of recovery diets containing 20% soya protein or 20% C. aconitifolius in place of soya protein or 10% soya proteins with 10% C. aconitifolius or commercial rat feed for 4 weeks, the recovery diet containing 10% soya and 10% C. aconitifolius caused the most significant (P malnourished group. The group fed with 20% C. aconitifolius in place of 20% soya protein also caused the most significant elevation in RBC, PCV and Hb compared with the malnourished group. The effects of diet containing 20% soya protein and commercial feed on PCV, Hb, platelet and all other haematological indices were not significantly different from each other (p

Sodium fluoride induces hypertension and cardiac complications through generation of reactive oxygen species and activation of nuclear factor kappa beta

Human exposure to sodium fluoride through its daily usage is almost inevitable. Cardiovascular and renal dysfunction has been associated with fluoride toxicity. Therefore, this study investigated the mechanism of action of sodium fluoride (NaF) induced hypertension and cardiovascular complications Forty male albino rats of an average of 10 rats per group were used. Group A received clean tap water. Toxicity was induced in Group B to D by administering graded doses of NaF through drinking water ad libitum for 10 days at 150 ppm, 300 ppm, and 600 ppm concentration respectively. Following administration of NaF, there was significant increase in systolic pressure, diastolic pressure and mean arterial pressure. Markers of oxidative stress; malondialdehyde, hydrogen peroxide, advance oxidation protein products, and protein carbonyl were significantly increased in dose‐dependent pattern in the cardiac and renal tissues of rats together with significant decrease in the GST activity in NaF‐treated rats compared to the control. Also serum markers of inflammation, cardiac, and renal damage including myeloperoxidase, xanthine oxidase, blood urea nitrogen, creatinine, Lactate dehydrogenase (LDH), and Creatinine kinase myocardial band (CK‐MB) significantly increased indicating induction of oxidative stress, renal, and cardiac damage after exposure. Histopathology of the kidney and heart revealed aberrations in the histological architecture in NaF‐treated rats. Also, immunohistochemistry showed higher expression of nuclear factor kappa beta (NF‐kB) in the cardiac and renal tissues of rats administered NaF. Combining all, these results indicate NaF‐induced hypertension through generation of reactive oxygen species and activation of renal and cardiac NF‐kB expressions.

Cyclophosphamide-induced hepatotoxicity in wistar rats: The modulatory role of gallic acid as a hepatoprotective and chemopreventive phytochemical

Background: Gallic acid (GA) is an endogenous plant phenol known to have antioxidant, free radical scavenging ability, anti-inflammatory, anti-cancer, and anti-fungal properties. The aim of this study was to assess the protective effect of GA on cyclophosphamide (CPA)-induced hepatotoxicity in male Wistar rats. Methods: Sixty rats were grouped into six groups of 10 rats per group. Group 1 received distilled water. Group 2 received CPA at 200 mg/kg single dose intraperitoneally on day 1. Groups 3 and 4 received a single dose of CPA (200 mg/kg) intraperitoneally on day 1 and then were treated with GA at 60 and 120 mg/kg body weight for 14 days, respectively. Rats in Groups 5 and 6 only received GA at 60 and 120 mg/kg body weight for 14 days, respectively. GA was administered orally. Results: CPA induced hepatic damage as indicated by significant elevation (P < 0.05) in aspartate aminotransferase, organ weight, and evidence by the histological study. CPA also induced hepatic oxidative stress as indicated by significant elevation (P < 0.05) in malondialdehyde content, hydrogen peroxide (H2O2) generation, nitrite level, and the level of glutathione (GSH) peroxidase crashed in the CPA-treated group. GA enhanced the antioxidant defense system as indicated by significant elevation (P < 0.05) in GSH level, catalase activity, and GSH-S-transferase activity. Conclusions: Taken together, the result of this present study shows that GA has a protective effect on CPA-induced hepatotoxicity.

Toxicological evaluations of methanolic extract of Moringa oleifera leaves in liver and kidney of male Wistar rats

Abstract Background: This study was conducted to investigate toxicological effects associated with prolonged consumption of Moringa oleifera leaves as a beverage. Methods: Thirty rats were used in this study. They were grouped into five groups of six rats. Rats in group I received 2 mL/kg body weight (b.w.) of corn oil (vehicle). Animals in groups II, III, IV and V received 50, 100, 200 and 400 mg/kg b.w. of methanolic extract of M. oleifera (MEMO) for 8 weeks. Serum collected was analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin, blood urea nitrogen (BUN) and creatinine. Results: There was a significant (p<0.05) increase in serum total protein and globulin in a dose-dependent manner. Rats that received MEMO at 200 and 400 mg/kg b.w. showed a significant (p<0.05) increase in serum ALT, AST, BUN and creatinine which pointed to hepatic and kidney damage. All experimental animals that received MEMO had a significant (p<0.05) increase in body weight in a dose-dependent manner. Conclusions: This study therefore confirms for the first time that chronic administration of M. oleifera leaves might predispose to hepatic and kidney damage.

Evaluation of the analgesic, anti-inflammatory, anti-oxidant, phytochemical and toxicological properties of the methanolic leaf extract of commercially processed Moringa oleifera in some laboratory animals

Abstract Background: Moringa oleifera Lam (Moringaceae) is a highly valued plant, distributed in many countries of the tropics and subtropics. It has an impressive range of medicinal uses with high nutritional value. Methods: The commercially processed M. oleifera was extracted using methanol as its solvent. Phytochemical analysis as well as the anti-oxidant properties of this supplement were also investigated. Acute toxicity was carried out in fasted mice. Carrageenan and histamine tests were used to assess anti-inflammatory effects in rats, while analgesic activities were assessed using the acetic acid-induced writhing test and formalin-induced paw lick test in mice. In the anti-oxidant tests, 1,1-diphenyl-2-picrylhydrazyl, ferrous reducing activity power, 2,21-azinobis-(3-ethylbenthialozine)-6-sulphonic acid and total polyphenolic (TPP) assays were deployed at concentrations of 10 mg/mL and 20 mg/mL. Results: The phytochemical analysis showed that the extract contained flavonoids, terpenoids, glycosides, tannins and saponins. In the acetic acid-induced writhing test, the extract significantly reduced the number of writhes at 100 and 200 mg/kg but not so much at 50 mg/kg. In the formalin-induced paw lick test, the effect was similar to that of the acetic writhing test. The analgesic effects were comparable to that of indomethacin used at 10 mg/kg. In the anti-inflammatory test, the extract reduced the formation of oedema especially at a dose of 200 mg/kg. In the anti-oxidant test, the extract was found to possess a free radical-scavenging property and is concentration related. Conclusions: The use of this extract for medicinal and nutritional purposes may have thus been justified; however, caution must be exercised in its use to prevent the toxic effect.

Hepatoprotective and in vivo antioxidant activities of ethanolic extract of whole fruit of Lagenaria breviflora

Abstract Background: This study was designed to investigate the hepatoprotective and in vivo antioxidant effects of the ethanol extract of whole fruit of Lagenaria breviflora (LB) in experimental animals. Methods: Forty nine Wistar albino rats were divided into seven groups of seven. Group I served as the control group; rats in Group II were given i.p. carbon tetrachloride (CCL4) (1.5 mL/kg) alone; Groups III–VI received different concentrations of plant extract (100, 250 and 500 mg/kg) with CCL4 and Group VII received kolaviron (KV) at 200 mg/kg as a reference hepatoprotective agent. Results: There was a significant (p<0.05) increase in malondialdehyde (MDA) and hydrogen peroxide (H202) generation in the serum of CCL4 treated rats (Group II) while the serum glutathione (GSH) level decreased significantly. Pretreatment with LB extract led to a significant (p<0.05) increase in serum GSH and a significant (p<0.05) reduction in MDA and H2O2generation. The activities of marker enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin, creatinine and blood urea nitrogen (BUN) increased (p<0.05) significantly in CCL4 treated rats (Group II). Conclusions: The present study suggested that treatment with LB extract enhances the recovery from CCL4 induced hepatic damage and oxidative stress via its antioxidant and hepatoprotective properties.