Iron transport & homeostasis mechanisms: their role in health & disease.

Iron is an essential trace metal required by all living organisms and is toxic in excess. Nature has evolved a delicately balanced network to monitor iron entry, transport it to sites of need, and serve as a unique storage and recycling system, in the absence of an excretory system, to remove excess iron. Due to the unique nature of iron metabolism, iron homeostasis is achieved by integrated specialized mechanisms that operate at the cellular and organism level. The use of positional cloning approaches by multiple researchers has led to the identification and characterization of various proteins and peptides that play a critical role in iron metabolism. These efforts have led to elucidation of the molecular mechanisms involved in the uptake of iron by the enterocytes, transportation across the membrane to circulation, and delivery to diverse tissues for use and storage and sensor system to co-ordinate and achieve homeostasis. Molecular understanding of these processes and the key regulatory molecules involved in maintaining homeostasis will provide novel insights into understanding human disorders associated with either iron deficiency or overload.

Lead hepatotoxicity & potential health effects.

Occupational and environmental exposures to lead (Pb), one of the toxic metal pollutants, is of global concern. Health risks are increasingly associated with environmental exposures to Pb emissions from, for example, the widespread use of leaded gasoline in developing countries. Exposure occurs mainly through the respiratory and gastrointestinal systems, and the ingested and absorbed Pb is stored primarily in soft tissues and bone. Autopsy studies of Pb-exposed patients have shown a large amount (approximately 33%) of the absorbed Pb in soft tissue stored in liver. In addition to neuronal encephalopathy observed in persons after exposure to very high concentrations of Pb, gastrointestinal colic (abdominal pain, constipation, intestinal paralysis) is a consistent early symptom of Pb poisoning in humans. Such severe gastrointestinal effects are consistently observed in patients with a blood Pb range of 30 to 80 microg/dl. Ingestion of Pb is one of the primary causes of its hepatotoxic effects. Hepatocarcinogenic effects of Pb reported in animal toxicology studies have led to new research into the biochemical and molecular aspects of Pb toxicology. Gains in the molecular understanding of Pb effects on hepatic drug metabolizing enzymes, cholesterol metabolism, oxidative stress, and hepatic hyperplasia suggest a potential role for Pb in damaging extrahepatic systems, including the cardiovascular system. This review also discusses the therapeutic potential of chelation therapy in treating Pb-induced hepatotoxicity in animals.