lithium-chloride and Birth-Weight

Functions of the kidney of mammals are immature during the neonatal period, and the neonatal kidney could be susceptible to chemicals, including drugs and environmental toxicants. Among these chemicals, cyclooxygenase (COX)-inducing chemicals should be given attentions as the potential kidney toxicants during the period, and we hypothesized that lithium chloride (LiCl) has such toxicity. Neonatal mice of C57BL/J strain were intraperitoneally injected with LiCl (2 mmol/kg body weight) daily until 21 days of age, and examined on 7 days and 21 days of age. Neonatal treatment of LiCl caused a significant increase in COX-2 mRNA and a decrease in mRNAs of aquaporins on day 7 of age. Osmolarity of urine from LiCl-treated neonates was significantly lower than that of control neonate. Most of the LiCl-treated neonates died during the second week of age. Histological examination revealed renal cysts on day 7 and hydronephrosis on day 21. in the surviving neonates. The present results showed that the kidney of mouse neonates is vulnerable to lithium, and suggested the possibility that COX-2 upregulation is responsible for the severe renal toxicity including hydronephrosis.

Topics: Animals; Animals, Newborn; Birth Weight; Cyclooxygenase 2; Female; Kidney; Lithium Chloride; Male; Mice; Mice, Inbred C57BL; RNA, Messenger

Natural lithium (Li) salts, including those used routinely in manic depressive illness, consist of two stable nonradioactive isotopes: lithium-7 (Li-7) (92.6%) and lithium-6 (Li-6) (7.4%). Female rats (3 months old) were treated with either Li-7 chloride or Li-6 chloride or were untreated prior to and during gestation and lactation. Birth weights were lower for Li-treated animals than for normal pups. Maternal behavior of all Li-treated mothers was altered. Li-7 mothers ignored their pups and nursed them infrequently. Li-6 mothers groomed and nursed their pups more often than normal mothers. All pups showed delays in development, especially in the maturation of depth perception. Although Li-6-treated dams were over-protective mothers, their offspring showed longer developmental delays than those of Li-7-treated offspring.

Topics: Animals; Behavior, Animal; Birth Weight; Chlorides; Depth Perception; Dose-Response Relationship, Drug; Female; Lithium; Lithium Chloride; Maternal Behavior; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred Strains