Cobalt chloride toxicity elicited hypertension and cardiac complication via induction of oxidative stress and upregulation of COX-2/Bax signaling pathway.

Cobalt is a ferromagnetic metal with extensive industrial and biological applications. To assess the toxic effects of, and mechanisms involved in cobalt chloride (CoCl2)-induced cardio-renal dysfunctions. Male Wistar rats were exposed orally, daily through drinking water to 0 ppm (control), 150 ppm, 300 ppm, and 600 ppm of CoCl2, respectively. Following exposure, results revealed significant ( p < 0.05) rise in markers of oxidative stress, but decreased activities of catalase, glutathione peroxidase, glutathione-S-transferase, and reduced glutathione content in cardiac and renal tissues. There were significant increases in systolic, diastolic, and mean arterial blood pressure at the 300- and 600-ppm level of CoCl2-exposed rats relative to the control. Prolongation of QT and QTc intervals was observed in CoCl2 alone treated rats. Also, there were significant increases in the heart rates, and reduction in P wave, and PR duration of rats administered CoCl2. Histopathology of the kidney revealed peritubular and periglomerular inflammation, focal glomerular necrosis following CoCl2 exposure. Further, cyclooxygenase-2 and B-cell associated protein X expressions were upregulated in the cardiac and renal tissues of CoCl2-exposed rats relative to the control. Combining all, results from this study implicated oxidative stress, inflammation, and apoptosis as pathologic mechanisms in CoCl2-induced hypertension and cardiovascular complications of rats.

Gallic acid protects against cyclophosphamide-induced toxicity in testis and epididymis of rats.

The protective role of gallic acid (GA) on reproductive toxicity induced by cyclophosphamide (CPA), an antineoplastic drug, was investigated in male Wistar rats. Sixty rats were grouped into 10 rats per group. Group 1 (control) received distilled water. Rats in groups 2 and 3 received GA alone at 60 and 120 mg kg(-1) for 14 consecutive days, respectively. Group 4 received a single intraperitoneal dose of CPA at 200 mg kg(-1) on day 1. Groups 5 and 6 received a single dose of CPA (200 mg kg(-1) ) intraperitoneally on day 1 followed by treatment with GA at 60 and 120 mg kg(-1) for 14 consecutive days, respectively. In testes and epididymis of the treated rats, CPA administration resulted in significant elevation (P < 0.05) in malondialdehyde (MDA), nitrite and hydrogen peroxide levels. There was a significant decrease in the activities of superoxide dismutase and glutathione-S-transferase. Furthermore, there were significant reductions in plasma luteinising hormone (LH), follicle stimulation hormone (FSH) and testosterone levels, which were accompanied by significant decrease in sperm motility and viability in CPA-treated rats. Histological examination revealed marked testicular and epididymal atrophy in CPA alone treated rats and these aberrations were reversed by GA. In conclusion, GA has capacity to protect against reproductive toxicity induced by cyclophosphamide.

The ethnobotanical, phytochemical and mineral analyses of phragmanthera incana (klotzsch), a species of mistletoe growing on three plant hosts in South-Western Nigeria.

Mistletoe is collected wildly on various plants and Phragmanthera incana is noted to grow on different plant hosts. This study was designed to carry out the ethnobotanical survey, phytochemical and mineral analyses of Phragmanthera incana, a species of mistletoe growing on three plant hosts namely Cocoa (Theobroma cacao), Kolanut (Cola nitida) and Bush mango (Irvingia gabonensis). Mistletoe samples were identified at the Forestry Research Institute of Nigeria Herbarium. Phragmanthera incana was screened for its phytochemical constituents and mineral cations along its hosts following standard methods and to confirm if the mistletoe species is host specific. The powdered samples of the mistletoe species (Phragmanthera incana) was used for both the phytochemical screening and the cation mineral analysis. The uses and the harvesting methods of mistletoe were also reviewed extensively in this paper.

Anti-inflammatory and analgesic activity of a cucurbitacin isolated from Lagenaria breviflora Roberty fruit.

BACKGROUND: In this study, the bioactive compound in Lagenaria breviflora Roberty responsible for its anti-inflammatory and analgesic activities was isolated and chemically characterized. METHOD: Compounds in the whole fruit, bark, pulp and seed of L. breviflora were partitioned utilizing their various polarity in n-hexane, ethyl acetate, chloroform and ethanol. The fractions of the extract obtained were tested for their bioactivities. The fraction with the most consistent anti-inflammatory and analgesic activities was further purified using accelerated gradient chromatography (AGC) and open column chromatography. Elution of compounds in this fraction was monitored through the different chromatography methods using thin layer chromatography (TLC). The pure compound isolated from the chromatography methods was taken for chemical characterization and elucidation of the structure. RESULTS: Ethyl acetate fraction of the whole fruit exhibited the most consistent anti-inflammatory and analgesic activities out of the 16 fractions obtained. Purification of this fraction with AGC yielded 7 subfractions composing of eluents with similar Rf values on the TLC plate. One of the sub-fractions yielded a compound which was further purified using the open column chromatography method. Eluent obtained from this sub-fraction was renamed YO1. CONCLUSION: From the result of mass spectroscopy and nuclear magnetic resonance spectroscopy of the compound, the structure of YO1 was determined as a cucurbitacin with 10á-cucurbit-5-ene skeleton (9â-methyl-19-norlanosta 5-ene) backbone structure, with six carbon atoms attached to double bonds and one hydroxyl group.

Pharmacological reactivity of isolated guinea pig ileum to ethanol leaf extracts of Amaranthus caudatus and Solanum melongena.

The pharmacological reactivity of guinea pig ileum to ethanol leaf extract of Amaranthus caudatus and Solanum melongena were determined in vitro. Parameters evaluated include the threshold value and the concentration ratio (CR). The potency of the plant extracts as expressed by EC50, the Emax (maximum response) and its corresponding concentration were determined from the concentration response curve in the absence or presence of 2X10-7 M atropine or 2X10-7 M mepyramine. The study showed that the extract of Amaranthus caudatus or Solanum melongena produced a dose-dependent contraction of the smooth muscle of the guinea pig ileum with threshold values at 80 or 100mg/ml respectively. 2X10-7 M atropine or 2X10-7 M mepyramine individually caused a right shift on the cumulative concentration-response curve for each plant extract. The potencies of the plant extracts were significantly decreased, and the concentration producing Emax was significantly increased in the presence of the antagonists. The ileal contraction produced by A. caudatus was more sensitive to mepyramine antagonism. The EC50 (373.80±51.56mg/ml) and the concentration producing Emax (855.00±75.00mg/ml) for A. caudatus extract increased significantly to 849.00±29.16 mg/ml and 875.00±25 respectively in the presence of atropine, indicating that the extract interacted with muscarinic receptors. The mean EC50 and the concentration eliciting the Emax for S. melongena extract increased significantly from 288.91±32.46mg/ml and 600.00±22.00mg/ml to 385.21±19.20mg/ml and 800±0.00 mg/ml respectively in the presence of mepyramine thus indicating stimulation of the histaminergic H1 receptors of the gastrointestinal tract. Taken together, this study demonstrated that A. caudatus predominantly stimulates muscarinic receptors to produce contraction of the gastrointestinal smooth muscle, while S. melongena predominantly stimulates histaminergic H1 receptors.

Anti-ulcerogenic and in vitro antioxidant activities of Lagenaria breviflora (LB) whole fruit ethanolic extract in laboratory animals.

BACKGROUND: The present study was undertaken to evaluate the anti-ulcer and antioxidant activities of the ethanol extract of Lagenaria breviflora (EELB) whole fruit in laboratory rats. METHODS: The anti-ulcer property of the ethanolic extract of the whole fruit of Lagenaria breviflora (LB) was assessed using the cold-restraint stress-induced (CRU) gastric ulcer, pyloric ligation-induced (PL) gastric ulcer, aspirin-induced (ASP) gastric ulcer and alcohol-induced (AL) gastric ulcer models. The scavenging activity of the LB extract was examined with 1, 1-diphenyl-2-picryl-hydrazyl (DPPH), Nitric oxide, Hydroxyl radical and Superoxide anion scavenging models. RESULTS: EELB (50, 100, 150 and 200 mg/kg, b.w.) protected against the CRU gastric ulcer dose dependently. Similarly, 150 mg/kg b.w. of the LB extract protected against the PL gastric ulcer, ASP gastric ulcer and AL gastric ulcer and was comparable to omeprazole (10 mg/kg b.w.) or Suscralfate (500 mg/kg b.w.), respectively. The in vitro antioxidant activity of LB was demonstrated by its ability to quench free radicals generated by nitric oxide and superoxide anion with a concomitant scavenging potential against DPPH-induced radical formation. CONCLUSION: Taken together, the study showed that the whole fruit extract possess potent anti-ulcer and antioxidant activities.

Anti-nociceptive and anti-inflammatory properties of the ethanolic extract of Lagenaria breviflora whole fruit in rat and mice.

The present study was conducted to evaluate the anti-nociceptive and anti-inflammatory properties of an ethanol extract of whole fruit of Lagenaria breviflora (LB) in rat and mice. Analgesic activity was measured by hot plate, formalin-induced paw licking, and acetic acid-induced abdominal writhing tests, while anti-inflammatory activity was determined by inhibition of carrageenan-induced paw oedema. Extract-treated animals exhibited significantly (P<0.05) higher pain threshold, lower number of licking of paws in response to formalin-induced irritation and writhing movements in response to acetic acid-induced writhing movement. There was significant (P<0.05) inhibition of carrageenan-induced paw oedema in rats pre-treated with the extract (50, 100, 200mg/kg) by 6.4%, 27.5%, 55.9% respectively. Analgesic effect of the extract (50, 100, 200mg/kg) in hot plate test was observable within 30 minutes of administration with maximum effect obtainable 90 minutes post-administration. Also, the effect of the extract (50, 100 and 200mg/kg) was dose dependent in both the early (88.17±6.21, 80.33±3.49 and 72.33±5.16) and late (72.50±3.95, 53.83±3.96 and 35.83±3.78) phases of formalin-induced paw licking, and in acetic acid-induced writhing with inhibition of 26.8%, 48.1% and 58.1% respectively. Its effect was comparable especially at 200mg/kg body weight to those of diclofenac, indomethacin and ibuprofen. It could be suggested from the findings of this experiment that the extract may be mediating its action as a central analgesic agent but the peripheral analgesic effect was preponderant based on its outcome from the pain models.

Hepatocellular carcinoma and the underlying mechanisms.

The incidence of hepatocellular carcinoma is increasing worldwide as well as the associated risk factors, some of which include exposure to aflatoxin B1, Hepatitis B (HBV) virus and hepatitis C (HCV) virus. Mutation of tumour suppressor gene p53 at codon 249(ser) at exon 7 has been found to contribute significantly to replication of damaged DNA and subsequent tumour progression. The x gene of HBV (HBx) is the most common open reading frame integrated into the host genome in hepatocellular carcinoma and the integrated HBx is frequently mutated in hepatocellular carcinoma. Mutant HBx proteins still retain their ability to bind to p53 thereby attenuating DNA repair and p53-mediated apoptosis.

Capsaicin: a novel chemopreventive molecule and its underlying molecular mechanisms of action.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the a principal pungent ingredient of hot red and chili peppers that belong to the plant genus Capsicum (Solanaceae). Capsaicin is a cancer-suppressing agent. It blocks the translocation of nuclear factor kappa B (NF-kB), activator protein 1 (AP-1), and signal transducer and activator of transcription (STAT3) signaling pathway that are required for carcinogenesis. The anti-inflammatory potential of capsaicin is attributed to its inhibitory effect on inducible COX-2 mRNA expression. Cytochrome P4502E1 mediates the activation of xenobiotics such as vinyl carbamate and dimethyl nitrosamine to their toxic metabolites. This metabolic activation of xenobiotics by Cytochrome P4502E1 has been shown to be inhibited by capsaicin. Capsaicin also generates reactive oxygen species in cells with resultant induction of apoptosis and cell cycle arrest, which is beneficial for cancer chemoprevention. Therefore, the use of capsaicin as a chemopreventive agent is of immense benefit for cancer chemoprevention. The search strategy included printed journals, pubmed, and medline, using the terms 'capsaicin' and 'anticancer' citations, relevant to anticancer properties of capsaicin.

Antidiabetic and haematinic effects of Parquetina nigrescens on alloxan induced type-1 diabetes and normocytic normochromic anaemia in Wistar rats.

BACKGROUND: The plant, Parquetina nigrescens is used in folklore medicine to treat diabetes mellitus and its complications in several parts of West Africa. OBJECTIVE: To determine the effect of Parquetina nigrescens extract on fasting blood glucose in alloxan-induced diabetic rats. METHODS: The blood glucose levels, complete blood count, erythrocyte indices and osmotic fragility, body and organ weights were evaluated. RESULTS: Diabetic rats treated with the extract showed significant (P<0.01) reduction of the blood glucose to levels comparable to that of the non-diabetic control and those treated with chlorpropamide (standard drug). Similarly, there was significant (P<0.01) reduction in the complete blood count in the diabetic rats. DISCUSSION: The anaemia, leucopenia and thrombocytopenia associated with the diabetes were corrected in the animals treated with the extract and chlorpropamide. The extract also reduced the erythrocyte osmotic fragility, body and organ weights. Parquetina nigrescens demonstrated antidiabetic property by reducing the elevated blood glucose in alloxan treated rats which is comparable to animals that received the standard drug. CONCLUSION: Paraquetina nigrescens stabilized the erythrocyte membrane, decreased the body weight probably by lowering lipogenesis. However, the mechanism underlying the antidiabetic and haematinic properties of Parquetina nigrescens remains to be elucidated.

Amelioration of carbon tetrachloride-induced hepatotoxicity and haemotoxicity by aqueous leaf extract of Cnidoscolus aconitifolius in rats.

This study was conducted to explore possible protective effect ofCnidoscolus aconitifolius (CA) leaf extract on carbon tetrachloride (CCl4)-induced hepatotoxicity and haemotoxicity in experimental animal models. Thirty six rats of six per group were used in this study. Group I received 10ml/kg normal saline as control. Group II-VI rats were administered with 1.25ml/kg body weight (bwt) of carbon tetrachloride intraperitonealy. Animals in groups III, IV, V and VI were however pre-treated with aqueous extract of Cnidoscolus aconitifolius at 100, 250, 500 and 750mg/kg body weight (bwt) respectively. Administration of CCL4 in untreated rats led to microcytic hypochromic anaemia, thrombocytopenia, increased erythrocyte fragility and stress induced leucocytosis accompanied with significant increase in neutrophils and decrease in lymphocyte counts. CCl4 also led to significant increase in serum transaminases (ALT and AST) and phosphatase (ALP) respectively compared with control animals. Also, CCL4 produced significant increase in serum blood urea nitrogen (BUN) and creatinine compared with normal rats. Pre-treatment with Cnidoscolus aconitifolius leaf extract brought about significant restoration of the haematological parameters to values that were comparable to those of the control with concomitant decrease in the activities of the marker of hepatic damage enzymes (ALT, AST and ALP), in a dose-dependent manner. Similarly, serum levels of blood urea nitrogen (BUN) and creatinine were also brought to near normal by the CA in a dose-dependent manner. From this study, we conclude that pre-exposure to Cnidoscolus aconitifolius leaf extract considerably reduced the effect of CCl4 on the blood parameters and ameliorated hepatic damage by the haloalkane.

Interactions between reactive oxygen species and cancer: the roles of natural dietary antioxidants and their molecular mechanisms of action.

Reactive oxygen species (ROS) are natural products inevitably generated along with cellular metabolism. Due to their extreme reactivity, they can damage DNA, proteins and lipids. Dietary antioxidants have been shown to take part in cellular reduction-oxidation (redox) reactions in which they can act as either antioxidants (election donors) or pro-oxidants (election acceptors) depending on the physiological environment and general oxidative state. Organisms have developed efficient machinery and mechanisms to keep the production of ROS under tight control, these same mechanisms have also been found to regulate other intracellular processes. p53 is a sequence-specific transcription factor and critical tumour suppressor gene that is most frequently mutated in human cancer. Cancer, one of the leading causes of death worldwide, can now be ameliorated, blocked or reversed with ubiquitous polyphenolic and organosulphur compounds present in natural dietary antioxidants.