chlordecone+CCl4hepatotoxicity.docVIP

Efficient tissue repair underlies the resiliency of postnatally developing rats to chlordecone + CCl4 hepatotoxicity. Dalu A, Mehendale HM. Source Division of Toxicology, College of Pharmacy and Health Sciences, Northeast Louisiana University, Monroe 71209-0470, USA. Abstract It is often assumed that at a younger age populations are at higher risk of toxic effects from exposure to toxic chemicals. Recent studies have demonstrated that neonate and postnatally developing rats are resilient to a wide variety of structurally and mechanistically dissimilar hepatotoxicants such as galactosamine, acetaminophen, allyl alcohol, and CCl4. Most interestingly, young rats survive exposure to the lethal combination of chlordecone CD + CCl4 known to cause 100% mortality in adult male and female rats. In a study where postnatally developing 20- and 45-day , and adult 60-day male Sprague Dawley rats were used, administration of CCl4 100 microliters/kg, i.p. alone resulted in transient liver injury regardless of age as indicated by plasma alanine transaminase ALT , sorbitol dehydrogenase SDH levels and histopathological lesions. In CD-pretreated rats, CCl4-induced toxicity progressed with time culminating in 25 and 100% mortality by 72 h after CCl4 in 45- and 60-day rats, respectively, in contrast to regression of CCl4-induced toxicity and 0% mortality in 20-day rats. [3H]Thymidine 3H-T incorporation and proliferating cell nuclear antigen PCNA studies revealed an association between delayed and diminished DNA synthesis, unrestrained progression of liver injury, and animal death. Time-course studies revealed that the loss of resiliency in the two higher age groups might be due to inability to repair the injured liver rather than due to infliction of higher injury. Intervention of cell division in 45-day CD rats by colchicine CLC, 1 mg/kg, i.p. 30 h after CCl4 challenge increased mortality from 25 to 85%, confirming the importance of stimulated tissue repair in animal s