Antimalarial Drugs Exacerbate Rat Liver Microsomal Lipid Peroxidation in the Presence of Oxidants

The study was undertaken to evaluate the effect of prior treatment of rats with the antimalarial drugs amodiaquine (AQ) mefloquine (MQ) and halofantrine (HF) on rat liver microsomal lipid peroxidation in the presence of 1 mM FeSO4, 1 mM ascorbate and 0.2 mM H₂O₂ (oxidants). Ingestion of -tocopheral, a radical chain-breaking antioxidant was also included to assess the role of antioxidants in the drug treatment. In the presence of oxidants AQ, MQ and HF elicited 288%, 175% and 225% increases in malondialdehyde (MDA) formation while the drugs induced 125%, 63% and 31% increases in the absence of oxidants respectively. Similarly, AQ, MQ and HF induced lipid hydroperoxide formation by 380%, 256%, 360% respectively in the presence of oxidants and 172%, 136% and 92% in the absence of exogenously added oxidants respectively. -tocopherol reduced AQ, MQ and HF-induced MDA formation by 40%, 55% and 52% respectively and lipid hydroperoxide formation by 53%, 59% and 54% respectively. Similarly, -tocopherol attenuated the AQ, MQ and HF-induced MDA formation by 49%, 51% and 51% in the presence of oxidants and lipid hydroperoxide formation by 61%, 62% and 47% respectively. The results indicate that rat liver microsomal lipid peroxidation could be enhanced by antimalarial drugs in the presence of reactive oxygen species and this effect could be ameliorated by treatment with antioxidants.     

Effect of vitamin E on monosodium glutamate induced hepatotoxicity and oxidative stress in rats

Monosodium glutamate (MSG), administered to rats (by gavage) at a dose of 0.6 mg/g body weight for 10 days, significantly (P<0.05) induced lipid peroxidation (LPO), decreased reduced glutathione (GSH) level and increased the activities of glutathione-s-transferase (GST), catalase and superoxide dismutase (SOD) in the liver of the animals; these were observed 24 hr after 10 days of administration. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT) were also significantly increased in the serum, on MSG administration. Vitamin E (0.2 mg/g body wt) co-administered with MSG, significantly reduced the LPO, increased the GSH level and decreased the hepatic activities of GST, catalase and SOD. The activities of ALT, AST and GGT in the serum were also significantly reduced. The results showed that MSG at a dose of 0.6 mg/g body wt induced the oxidative stress and hepatotoxicity in rats and vitamin E ameliorated MSG-induced oxidative stress and hepatotoxicity.     

Ex-vivo and in vitro protective effects of kolaviron against oxygen-derived radical-induced DNA damage and oxidative stress in human lymphocytes and rat liver cells

The present study reports the protective effects of kolaviron, a Garcinia biflavonoid from the seeds of Garcinia kola widely consumed in some West African countries against oxidative damage to molecular targets ex-vivo and in vitro. Treatment with hydrogen peroxide (H2O2) at a concentration of 100 micromol/L increased the levels of DNA strand breaks and oxidized purine (formamidopyrimidine glycosylase (FPG) and pyrimidine (endonuclease III (ENDO III) sites) bases in both human lymphocytes and rat liver cells using alkaline single cell gel electrophoresis (the comet assay). Kolaviron was protective at concentrations between 30-90 micromol/L and decreased H2O2-induced DNA strand breaks and oxidized bases. Neither alpha-tocopherol nor curcumin decreased H2O2-induced DNA damage in this assay. In lymphocytes incubated with Fe3+/GSH, Fe3+ was reduced to Fe2+ by GSH initiating a free radical generating reaction which induced 11.7, 6.3, and 4.9 fold increase respectively in strand breaks, ENDO III and FPG sensitive sites compared with control levels. Deferoxamine (2 mmol/L), an established iron chelator significantly inhibited GSH/Fe3+-induced strand breaks and oxidized base damage. Similarly, kolaviron at 30 and 90 micromol/L significantly attenuated GSH/Fe3+-induced strand breaks as well as base oxidation. Kolaviron (100 mg/kg bw) administered to rats for one week protected rat liver cells against H2O2-induced formation of strand breaks, ENDO III, and FPG sensitive sites, Fe3+/EDTA/ascorbate-induced malondialdehyde formation and protein oxidation using gamma-glutamyl semialdehyde (GGS) and 2-amino-adipic semialdehyde (AAS) as biomarkers of oxidative damage to proteins. We suggest that kolaviron exhibits protective effects against oxidative damage to molecular targets via scavenging of free radicals and iron binding. Kolaviron may therefore be relevant in the chemoprevention of oxidant-induced genotoxicity and possibly human carcinogenesis.     

Fused pyrimidine based inhibitors of phosphodiesterase 7 (PDE7): synthesis and initial structure-activity relationships

A series of fused pyrimidine based inhibitors of PDE7 have been derived from an earlier screening lead 1. The synthesis, structure-activity relationships (SAR) and selectivity against several other PDE family members are described.     

Artemisia afra Jacq. ameliorates oxidative stress in the pancreas of streptozotocin-induced diabetic Wistar rats

Diabetes is characterized by hyperglycemia resulting from defects in pancreatic insulin secretion and/or impaired target cell responsiveness to insulin, and Artemisia afra Jacq. is widely used in South Africa to treat the disease, but the mechanism of action is yet to be elucidated. This study explored the effect of oral administration of aqueous leaf extract of A. afra on the pancreas of streptozotocin-induced diabetic rats. We found that the extract significantly reduced blood glucose levels, accompanied by an increase in the serum insulin concentration. Moreover, the antioxidant enzymic activities of glutathione peroxidase, glutathione reductase, and superoxide dismutase also improved significantly after treatment with the extract. Increased pancreatic lipid peroxidation in the diabetic rats was also normalized by the extract. This study indicates that A. afra possesses hypoglycemic and antioxidant activities. Our findings suggest that the herb might exert its anti-diabetic activity by regenerating pancreatic beta cells, thereby stimulating the release of insulin.     

Comparison of divalent transition metal ion paraCEST MRI contrast agents

Transition-metal-ion-based paramagnetic chemical exchange saturation transfer (paraCEST) agents are a promising new class of compounds for magnetic resonance imaging (MRI) contrast. Members in this class of compounds include paramagnetic complexes of Fe^II, Co^II, and Ni^II. The development of the coordination chemistry for these paraCEST agents is presented with an emphasis on the choice of the azamacrocycle backbone and pendent groups with the goals of controlling the oxidation state, spin state, and stability of the complexes. Chemical exchange saturation transfer spectra and images are compared for different macrocyclic complexes containing amide or heterocyclic pendent groups. The potential of paraCEST agents that function as pH- and redox-activated MRI probes is discussed.     

The food and feeding habits of Eutropius niloticus (Ruppell), family Schilbeidae (Osteichthyes: Siluriformes) in Lake Kainji,Nigeria

Studies on the food and feeding habits of Eutropius niloticus in Lake Kainji, Nigeria revealed that the fish is omnivorous but fed more on insects than on any other food. The most important insects were Povilla adusta Navas nymphs and imagos and adults of the common grasshoppers. Fish, particularly the clupeids Sierrathrissa leonensis Thys Van den Audernaerde and Pellonula afzeliusi Johnels, also formed an important part of the diet. There was seasonal variation of organisms selected for food and there were variations in the dietary items selected by different age groups. Accumulation of fat was found to correlate with seasonal feeding intensity. E. niloticus serves as food for other fishes.     

Digestive enzymes in the alimentary tracts of three tropical catfish

Digestive enzymes in the guts of Physailia pellucida, Eutropius niloticus and Schilbe mystus were investigated. Trypsin and Pepsin were present in all the three species. Pepsin activity was found to be higher than that of trypsin. Of all the carbohydrases, only amylase was found in E. niloticus and S. mystus, none in P. pellucida. There was no lipase activity in the three species. The enzymes were correlated with the food habits of the species.     

Economic Evaluations of Adult Male Circumcision for Prevention of Heterosexual Acquisition of HIV in Men in Sub-Saharan Africa: A Systematic Review

Background

There is conclusive evidence from observational data and three randomized controlled trials that circumcised men have a significantly lower risk of becoming infected with the human immunodeficiency virus (HIV). The aim of this study was to systematically review economic evaluations on adult male circumcision (AMC) for prevention of heterosexual acquisition of HIV in men.

Methods and Findings

Studies were identified from the following bibliographic databases: MEDLINE (Ovid), EMBASE (Ovid), Cochrane Library (Wiley''s internet version), NHS EED and DARE Office of Health Economics HEED. The searches were conducted in November 2009. The Drummond 10-point checklist was used for methodological critique of the economic evaluations. Cost data were inflated and converted to 2008 US dollars (US$). Of 264 identified papers, only five met the inclusion criteria and were included in the review. The studies were published between 2006 and 2009. Most of the studies were carried out from the perspective of government healthcare payer. The time horizon ranged from 10 to 20 years. All studies reported that AMC is cost-effective. The reported cost per HIV infection averted ranged from US$174 to US$2808. The key driver of the cost-effectiveness models was circumcision efficacy.

Conclusions

All published economic evaluations offered the same conclusion that AMC is cost-effective and potentially cost-saving for prevention of heterosexual acquisition of HIV in men. On these grounds, AMC may be seen as a promising new form of strategy for prevention of HIV and should be implemented in conjunction with other evidence-based prevention methods.