Metabolic response to subacute and subchronic iron overload in a rat model.

One of the common causes of iron overload is excessive iron intake in cases of iron-poor anemia, where iron saccharate complex (ISC) is routinely used to optimize erythropoiesis. However, non-standardized ISC administration could entail the risk of iron overload. To induce iron overload, Wistar rats were intraperitoneally injected with subacute (0.2 mg kg⁻¹) and subchronic (0.1 mg kg⁻¹) overdoses of ISC for 2 and 4 weeks, respectively. Iron status was displayed by an increase in transferrin saturation (up to 332%) and serum and liver iron burden (up to 19.3 µmol L⁻¹ and 13.2 µmol g⁻¹ wet tissue, respectively) together with a drop in total and unsaturated iron binding capacities "TIBC, UIBC" as surrogate markers of transferrin activity. Iron-induced leukocytosis (up to 140%), along with the decline in serum transferrin markers (up to 43%), respectively, mark positive and negative acute phase reactions. Chemical stress was demonstrated by a significant rise (p > 0.05) in indices of the hemogram (erythrocytes, hemoglobin, hematocrit, leukocytes) and stress metabolites [corticosterone (CORT) and lactate]. Yet, potential causes of the unexpected decline in serum activities of ALT, AST and LDH (p > 0.05) might include decreased hepatocellular enzyme production and/or inhibition or reduction of the enzyme activities. The current findings highlight the toxic role of elevated serum and liver iron in initiating erythropoiesis and acute phase reactions, modifying iron status and animal organ function, changing energy metabolism and bringing about accelerated glycolysis and impaired lactate clearance supposedly by decreasing anaerobic threshold and causing premature entering to the anaerobic system.

Protective role of indomethacin on lipopolysaccharide-stimulated fever induction and cerebral catecholamine biosynthesis in Wistar rat.

OBJECTIVES: The antipyretic and neuroprotective potential of the nonsteroidal anti-inflammatory drug "indomethacin" was tested against lipopolysaccharide-produced hyperthermia and biosynthesis of norepinephrine and dopamine, in six brain regions of male rat. METHODS: Observations were based on a single intraperitoneal injection of each of lipopolysaccharide (250 µg Kg-1 body wt) and indomethacin (20 mg Kg-1 body wt) followed by sampling and assaying of brain specimens after 2, 8, 12 and 24 hrs. lipopolysaccharide induced a general hyperthermia (8-24 hr) that was completely abolished by pretreatment with indomethacin. RESULTS: In virtually all brain regions tested, lipopolysaccharide stimulated the biosynthesis of norepinephrine and dopamine. Yet, pretreatment with indomethacin provoked substantial mitigation predominantly after 24 hrs. A time-based manner attended by a regionally nonselective manner characterized lipopolysaccharide-induced monoamine biosynthesis; whereas, indomethacin alleviation seems to proceed in a time-dependent and regionally-selective pathway since the pons proved the fastest and/or most responsive brain region to indomethacin action. A role of prostaglandin synthesis in the development of lipopolysaccharide-induced fever and catecholamine biosynthesis was suggested, given that both responses were abolished by the cyclooxygenase-inhibitor indomethacin. CONCLUSION: Accordingly, our data verified the potent therapy potential of indomethacin in protecting cerebral noradrenergic and dopaminergic systems against lipopolysaccharide-induced acute phase reactions.

Impact of heavy metal pollution on the hemogram and serum biochemistry of the Libyan jird, Meriones libycus.

The stress profiles of the hemogram and serum biochemistry were determined in the context of heavy metal (Cd, Cu, Hg, Ni and Pb) exposure in the wild libyan jird, Meriones libycus, from one of Riyadh's polluted areas versus a reference site. Coupling the pronounced drop in platelets (PLT) (28%) and mean platelet volume (MPV) (17%) with the insignificant responses of other red blood cell indices, suggests bone marrow suppression that is characterized by thrombocytopenia as an initial abnormality. The species-specific stress leukogram for M. libycus is expressed by leukocytosis (66%), monocytosis (40%), lymphocytosis (23%) with eosinopenia (81%) and neutropenia (42%). Hyperglycemia (50%), hyper-low-density-lipoproteinemia (38%), hypocortisolism (85%) and hypotriglyceridemia (55%) depicted serum biochemistry profile. In polluted jirds, the elevated activities of pseudocholinesterase (PChE) and serum marker enzymes (alanine aminotransferase ALT, aspartate aminotransferase AST and creatine kinase CK) strongly suggest functional damage of the liver and/or heart. A potential role of PChE in low-density lipoprotein (LDL) metabolism is implied in the joint rise of both indices and in the recognized relationship between PChE and lipid metabolites. While increased utilization in lipid metabolism and energy synthesis could rationalize the inhibition of the normal patterns of triglycerides and lactate dehydrogenase (LDH), the inhibited activities of LDH could additionally be attributed to its hormetic behavior towards low and high metal concentrations. The overall findings presented here documented the relevance of M. libycus in biomonitoring and predicting the risk imposed on human populations living in polluted areas.

Risk assessment of heavy metal contamination in soil and wild Libyan jird Meriones libycus in Riyadh, Saudi Arabia.

This study was undertaken to document the impact of heavy metal pollution on the Libyan jird, Meriones libycus and to contribute to an environmental impact statement for the rapidly growing City of Riyadh. All metal concentrations in surface soil of a polluted site (within Riyadh City) were higherthan those from a reference site (outside the city).Although Pb declined versus earlier reports on Riyadh soil, Cd (0.97 microg g(-1)) and Hg (0.28 microg g(-1)) were above some of the most stringent quality guidelines (0.07-0.62 microg g(-1) for Cd and 0.14-0.18 microg g(-1) for Hg). Metal distribution in M. libycus proved site-related and organ-specific, recognizing a higher affinity of most tested metals towards the kidneys, liver and brain than the lung and heart. The comparatively lower site-specific accumulation of Pb in soft tissues was attributed primarily to its major hypothetical accumulation in bones, whereas, the transition rate of Hg from the liver was suggested to be lower to the brain than to the kidneys. Although a non hazardous status was assumed for Cu (11.27-13.16 microg g(-1)) and Hg (up to 0.207 microg g(-1)) in tissues of M. libycus, a potential risk was imposed by mean tissue concentrations of Cd (up to 3.29 microg g(01)), Ni (up to 1.48 microg g(-1)) and Pb (up to 1.94 microg g(-1)). On the grounds of the significantly higher metal levels in polluted soft tissues versus reference subjects, Libyan jirds possess high exposure potential and can be useful biomonitors of environmental metal contamination.