High-fat diet induced obesity promotes inflammation, oxidative stress, and hepatotoxicity in female FVB/N mice.

Although obesity and subsequent liver injury are increasingly prevalent in women, female mouse models have generally shown resistance to high-fat diet (HFD)-induced obesity. We evaluated control and HFD-fed male and female FVB/N mice, a strain well-suited to transgenic analyses, for phenotypic, histological, and molecular markers related to control of glucose, lipids, and inflammation in serum, liver, and perigonadal white adipose tissues. Unlike many mouse models, HFD-fed FVB/N females gained more perigonadal and mesenteric fat mass and overall body weight than their male counterparts, with increased hepatic expression of lipogenic PPARγ target genes (Cd36, Fsp27, and Fsp27ß), oxidative stress genes and protein (Nqo1 and CYP2E1), inflammatory gene (Mip-2), and the pro-fibrotic gene Pai-1, along with increases in malondialdehyde and serum ALT levels. Further, inherent to females (independently of HFD), hepatic antioxidant heme oxygenase-1 (HMOX1, HO-1) protein levels were reduced compared to their male counterparts. In contrast, males may have been relatively protected from HFD-induced oxidative stress and liver injury by elevated mRNA and protein levels of hepatic antioxidants BHMT and Gpx2, increased fatty acid oxidation genes in liver and adipocytes (Pparδ), despite disorganized and inflamed adipocytes. Thus, female FVB/N mice offer a valuable preclinical, genetically malleable model that recapitulates many of the features of diet-induced obesity and liver damage observed in human females.

Evaluation of efficacy and safety of a herbal medicine used for the treatment of malaria.

Resistance of Plasmodium falciparum to chloroquine has been reported in several countries. Other anti-malarial drugs in use are expensive and not readily accessible to most people in malaria endemic countries. This has led to renewed interest in the development of herbal medicines that have the potential to treat malaria with little or no side effects. This study obtained a preliminary information on the safety and effectiveness of a plant decoction (AM-1), used in treating malaria. The AM-1 is formulated from Jatropha curcas, Gossypium hirsutum, Physalis angulata and Delonix regia. Patients with suspected malaria attending a herbal clinic were enrolled in the study on voluntary basis. They were hospitalized for treatment, clinical observation, biochemical and haematological monitoring, and parasite clearance while on AM-1. In addition male and female Sprague Dawley rats were used to evaluate the acute and subchronic toxicity effects of AM-1. The AM-1 eliminated malaria parasites (Plasmodium falciparum and Plasmodium malarie) from the peripheral blood of patients with malaria. In addition the AM-1 did not show any undesired effects in the patients as well as in laboratory rats. The AM-1, however, showed differential effect on the activities of selected cytochrome P450 isozymes (7-pentoxyresorufin-O-depentylation, 7-ethoxyresorufin-O-deethylation and p-nitrophenol hydroxylase) in relation to sex of the laboratory rats. These results indicate that AM-1 could be used to treat malaria. However, it could precipitate interactions with other drugs via their biotransformation and elimination. The obtained data warrant further studies in a large number of malaria subjects with monitoring for possible drug interactions.