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.

Acute coumaphos organophosphate exposure in the domestic dogs: Its implication on haematology and liver functions.

Indiscriminate use of organophosphate acaricides especially among livestock and dog owners in the control of ticks and other ectoparasites has taken a worrisome dimension. In the present study, we investigated, the effects of acute dermal exposure in the form of acaricides baths of coumaphos at different concentrations on the haematology, blood pressure and liver functions in local mongrel dogs. Twenty-four, male mongrel dogs of about 8 months of age with an average weight of 9.88 ±â€¯0.4 kg were used for the study. The dogs were divided into four groups consisting of six dogs per group. Group A (control) was bathed with ordinary water, while group B was bathed with the recommended concentration of 0.016% (160 ppm) Coumaphos in water. Groups C and D were bathed with 10 and 20 times the recommended dose (1600 ppm and 3200 ppm), respectively. Significant leucopenia, increased plasma urea and decreased low density lipoprotein (LDL) values were observed at 8 h post exposure, which worsened with time. At 24 and 36 hrs post exposure, normochromic normocytic anaemia, pan leucopenia, bloody diarrhoea, retching, vomiting and paddling were observed in affected animals. Post mortem examination revealed severe lungs, liver and stomach congestion. Multifocal areas of necrosis in the liver and kidney, serosal and mucosal haemorrhages and haemorrhagic meningitis were also observed. The use of excessively high concentration of organophosphate as acaricides bath is associated with severe anticholinesterase poisoning, which may result in death of affected animals.

Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by kolaviron, a natural bioflavonoid of Garcinia kola seeds.

The chemopreventive effects of kolaviron, a natural antioxidant bioflavonoid from the seeds of Garcinia kola, on aflatoxin B1 (AFB1)-induced genotoxicity and hepatic oxidative damage was investigated in rats. Kolaviron administered orally at a dose of 200 mg/kg once a day for the first 2 weeks and then 100 mg/kg twice a day for the last 4 weeks of AFB1 (2 mg/kg, single dose, intraperitoneal) treatment reduced the AFB1-increased activities of aspartate amino transferase (AST), alanine amino transferase (ALT) and gamma glutamyltransferase (gamma-GT) by 62%, 56% and 72% respectively. Malondialdehyde (MDA) formation and lipid hydroperoxide (LHP) accumulation were observed in the livers of AFB1-treated rats. Kolaviron significantly reduced the AFB1-induced MDA and LHP formation. Vitamins C and E were protective in reducing the increase in the activities of AST, ALT and gamma-GT as well as lipid peroxidation caused by AFB1 (P<0.01). Administration of rats with kolaviron alone resulted in significant elevation in the activities of glutathione S-transferase, uridyl glucuronosyl transferase and NADH:quinone oxidoreductase by 2.45-, 1.62- and 1.38-folds respectively. In addition, kolaviron attenuated the AFB1-mediated decrease in the activities of these enzymes (P<0.01). Pretreatment of rats with kolaviron, vitamins C and E alone did not exert genotoxicity assessed by the formation of micronucleated polychromatic erythrocytes (MNPCEs) (P>0.05). Co-treatment of rats intraperitoneally with kolaviron (500 mg/kg) 30 min before and 30 min after AFB1 (1 mg/kg) administration inhibited the induction of MNPCEs by AFB1 (P<0.001) after 72 h. While vitamin C was effective in reducing AFB1-induced MNPCEs formation, vitamin E did not elicit any antigenotoxic response. These results indicate kolaviron as effective chemopreventive agent against AFB1-induced genotoxicity and hepatic oxidative stress. Thus kolaviron may qualify for clinical trial in combating the menace of aflatoxicosis in endemic areas of aflatoxin contamination of foods.

Evaluation of valuation of toxicity profile of an alkaloidal fraction of the stem bark of Picralima nitida (fam. Apocynacaes).

Dermal and acute toxicity evaluation of the basic alkaloidal fraction of the stem bark of Picralima nitida, which has been shown to have pronounced activity against causative organisms of dermatomycosis in man, was carried out in animals. Acute intraperitoneal toxicity tests showed a dose-dependent toxicity. There was inflammation and necrosis of liver hepatocytes accompanied by reduction in neutrophilic count and a corresponding increase in lymphocytic count. There was no sign of reddening or irritation when applied into the eye conjunctiva. Dermal tests also showed that the fraction caused no sensitization, inflammation or death in the animal models used.