Effect of chemical form, route of administration and vehicle on 3,5‐dichloroaniline‐induced nephrotoxicity in the fischer 344 rat

Abstract

Chloroanilines are widely used chemical intermediates for the manufacture of dyes, agricultural chemicals and industrial compounds. Nephrotoxicity occurs as one toxicity following intraperitoneal (i.p.) administration of chloroaniline hydrochlorides to rats. The purpose of this study was to examine the effect of chemical form, route of administration and vehicle on 3,5-dichloroaniline-induced nephrotoxicity. In one set of studies, male Fischer 344 rats (four to eight per group) were administered a single i.p. injection of 3,5-dichloroaniline free base or hydrochloride salt, cysteine hydrochloride or ornithine hydrochloride (0.8, 1.0 or 1.5 mmol kg-1) or an appropriate vehicle and renal function monitored for 48 h. Only 3,5-dichloroaniline hydrochloride induced nephrotoxicity that was characterized as acute renal failure. When 3,5-dichloroaniline free base (0.8 mmol kg-1) was administered in dimethyl sulfoxide (DMSO), all rats died within 24 h. In a second experiment, the free base or hydrochloride form of 3,5-dichloroaniline (1.5 mmol kg-1) or vehicle (0.9% saline or sesame oil, respectively) were administered orally and renal function monitored for 48 h. No evidence of nephrotoxicity was observed following either treatment. However, when the hydrochloride salt was given in 25% DMSO in 0.9% saline, all rats died within 24 h, with two rats demonstrating increased proteinuria, glucosuria and hematuria within the first 6 h after treatment. These results demonstrate that 3,5-dichloroaniline nephrotoxicity is potentiated by the administration of systemic acid, but that acid alone has no effect on renal function at the dose tested. Also, 3,5-dichloroaniline (hydrochloride or free base form) is less toxic orally than when administered i.p.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of biotransformation and oxidative stress in 3,5-dichloroaniline (3,5-DCA) induced nephrotoxicity in isolated renal cortical cells from male Fischer 344 rats

“…Males were chosen for these experiments because our previous studies were performed in male rats (Lo et al, 1994; Valentovic et al, 1995b). All pretreatment times and concentrations were based on previously published studies (Baliga et al, 1998; Harleton et al, 2004.…”

Sleep-Aids Derived from Natural Products

“…Magnolia ( M. obovate , M. officinalis , Magnoliaceae) has been traditionally used for the treatment of thrombotic stroke, depression, anxiety, and inflammatory and neuronal diseases in oriental countries for a long time ( Watanabe et al ., 1983 ; Hirano, 1991 ; Lo et al ., 1994 ). Biophenolic compounds such as magnolol, honokiol, and obovatol isolated from M. obovate / and M. officinalis have been found to be anxiolytic and muscle relaxant ( Maruyama et al ., 1998 ; Seo et al ., 2007 ; Han et al ., 2010 ).…”

Aromatic Nitro and Amino Compounds

“…Further studies examined this effect more thoroughly. When administered intraperitoneally in dimethyl sulfoxide solution, the rats died within 24 h; if given as a solution in saline or sesame oil, no renal toxicity was noted (189). Treatment of rats with various enzyme inducers and inhibitors and then 3,5-dichloroaniline did not cause much change in the renal or hepatic effects of the 3,5-isomer.…”