Prevention of lithium nephrotoxicity in a novel one-hour model in rats

Abstract

It is well established that lithium can cause morphologically visible damage to the kidneys of humans and animals. Although the clinical significance of its nephrotoxicity is debatable, it would be desirable to find a method to prevent lithium's effect on the kidneys. Toward this end, we have developed a novel method for producing nephrotoxicity that will be useful for research on prevention. A single, large, toxic dose of lithium chloride (LiCl) caused necrosis of the distal convoluted tubules, which was visible by light microscopy in 30 min, had fully developed in 1 h, and had disappeared by the next day. The lesions were seen after i.p. or i.v. injections of fasted rats of three different strains. Equivalent doses of NaCl, KCl, MgCl2 and combinations thereof had no such effect, nor did they inhibit nephrotoxicity when incorporated into the LiCl solution. However, relatively small doses of LiCl injected by any route 3 or 24 h beforehand prevented the nephrotoxicity. The mechanism of prevention is not known, but it does not involve reduction of lithium levels in the kidneys.

β-Catenin promotes host resistance against Pseudomonas aeruginosa keratitis

“…[34]. For in vitro interference, murine macrophage-like RAW264.7 cells and mouse bone marrow–derived neutrophils were cultured in the media with additional 10 mM LiCl versus NaCl [35].…”

“…LiCl (Sigma, St. Louis, MO) or appropriate control NaCl (Sigma) was subconjunctivally injected into the left eye of B6 mice (5 µl/mouse at a concentration of 0.15 M, n=5/group/time) 1 day before infection and then topically applied to the infected corneas (5 µl/mouse per time at an isotonic concentration of 0.15 M, once on the day of infection, and twice on both 1 and 3 days p.i.) [ 34 ]. For in vitro interference, murine macrophage-like RAW264.7 cells and mouse bone marrow–derived neutrophils were cultured in the media with additional 10 mM LiCl versus NaCl [ 35 ].…”

Early targets of lithium in rat kidney inner medullary collecting duct include p38 and ERK1/2

“…The selected dosage is far from the previously identified acute Linephrotoxic dose (1 mmol/100 mg body weight, intraperitoneal). 28 For protocol 2 (n ¼ 8 in each group), 1 h before LiCl administration, rats received an oral gavage of inhibitors of pERK1/2 (PD0325901, Selleckchem, Houston, TX) and pP38a (SB203580, Biosource, Camarillo, CA, 10 and 20 mg/kg body weight in 15% DMSO, respectively) or vehicle (15% DMSO). Similar dosages were efficacious in other studies in vivo.…”

Influence of Strain, Sex and Age on Nephrotoxicity of Lithium in a One-Hour Model in Rats

“…Minor side effects on renal function are common and serious nephrotoxicity occurs occasionally. Models of lithium nephrotoxicity in animals required many days or weeks of treatment until a 1-hour procedure was described [1]. This method produces extensive cell death in distal convoluted and cortical collecting tubules 1 h after injection of a large dose of LiCl in fasted rats.…”