Molecular detection and characterization of a novel Theileria genotype in Dama Gazelle (Nanger dama).

Wild animals play a critical role in maintenance and transmission of various tick-borne pathogens. It is essential to identify these wild host species that can serve as important reservoirs of tickborne diseases. In the present study we investigated Dama gazelle (Nanger dama) as a potential novel reservoir of Theileria spp. A total of 53 blood samples collected from Dama gazelle as part of the Al Ain Zoo preventive medicine program were screened for Theileria spp. by qPCR using a commercial assay, followed by additional studies using conventional PCR targeting an approximate 450-base pair (bp) fragment of the V4 hypervariable region of the 18S ribosomal RNA (rRNA) gene. Sequencing and phylogenetic analysis of a subset (20) of PCR amplicons revealed Theileria isolates from gazelles of Al Ain Zoo clustered closely to Theileria sp. Dama Gazelle (AY735115) from USA and were far away or did not cluster with the known Theileria spp. of ruminants namely T. annulata, T. ovis, T. orientalis, T. luwenshuni, T.parva and T.sinensis. Theileria genotypes detected in gazelles of present study were clearly distinct from the other common theileria species of ruminants. The present finding throws light on the critical role of reservoir host in maintenance and transmission of pathogen.

Increased mitochondrial stress and modulation of mitochondrial respiratory enzyme activities in acetaminophen-induced toxicity in mouse macrophage cells.

Overdose of acetaminophen (APAP) causes tissue injury particularly in the liver. However, the precise mechanism of APAP toxicity is not clear. Glutathione (GSH) depletion and oxidative stress are believed to be the main cause of APAP toxicity. The role of macrophages in APAP-induced tissue injury is controversial. Using mouse macrophage J774.2 cells, we recently demonstrated that like in animal models, APAP reduces GSH pool and alters GSH metabolism by increasing the production of reactive oxygen species (ROS). In the present study, we show that APAP-induced cytotoxicity and apoptosis in macrophages are associated with increased mitochondrial metabolic and oxidative stress, alterations in the mitochondrial membrane potential and activities of the respiratory enzyme complexes. APAP treatment also altered ROS/NO production and inhibited the expression of COX-2 and iNOS in LPS-stimulated macrophages. Electron microscopic studies also confirmed morphological changes associated with apoptosis at the lower dose of APAP, while at the higher dose late apoptosis/necrotic changes were visible. These results suggest that mitochondrial metabolic and oxidative stress are the main causes of cytotoxicity and cell death in APAP treated macrophages. The study may have long term implications to better understand the role of macrophages in the toxicology and pharmacology of APAP.

Redox homeostasis and respiratory metabolism in camels (Camelus dromedaries): comparisons with domestic goats and laboratory rats and mice.

We have previously reported the occurrence of multiple forms of drug-metabolizing enzymes in camel tissues. Here, we investigate glutathione (GSH)-dependent redox homeostasis, reactive oxygen species (ROS) production and mitochondrial respiratory functions in camel tissues and compare them with imported domestic goats and laboratory rats and mice. Cytochrome P450 2E1 (CYP 2E1) and GSH-metabolizing enzymes were differentially expressed in the liver and kidney of these animals. Camel liver has significantly lower GSH pool than that in goats, rats and mice. Mitochondria isolated from the tissues of these animals showed a comparable ability to metabolize specific substrates for respiratory enzyme complexes I, II/III and IV. These complexes were metabolically more active in the kidney than in the liver of all the species. Furthermore, the activity of complex IV in camel tissues was significantly lower than in other species. On the other hand, complex II/III activity in camel kidney was higher compared to the other species. In addition, as expected, we observed that inhibitors of these enzyme complexes augment the production of mitochondrial ROS in camel and goat tissues. These results help to better understand the metabolic ability and adaptation in desert camels in comparison with domestic goats and laboratory rats and mice since they are exposed to different environmental and dietary conditions. Our study may also have implications in the pharmacology and toxicology of drugs and pollutants in these species.