Acute effects of 2-bromopropane and 1,2-dibromopropane on hepatotoxic and immunotoxic parameters in female BALB/c mice

Abstract

In the present studies, the acute toxic effects of 2-bromopropane (2-BP) and its analog, 1,2-dibromopropane (1,2-DBP), were investigated in female BALB/c mice. The mice were treated orally with either 2-BP at 2000 and 4000 mg/kg or 1,2-DBP at 300 and 600 mg/kg. Four days before necropsy, the mice were immunized intraperitoneally with sheep red blood cells (SRBCs). 1,2-DBP reduced the weights of the spleen and thymus weights and decreased the number of splenic cells. In addition, treatment with 1,2-DBP suppressed the antibody response to SRBCs. Meanwhile, only the antibody response was significantly suppressed by treatment with 2-BP. In the subsequent studies, the time course effects of 2-BP and 1,2-DBP on the hepatotoxic parameters were compared in female BALB/c mice. When mice were treated orally with either one of these chemicals for 6, 12, 24 and 48 h, the activities of serum alanine aminotransferase and aspartate aminotransferase elevated significantly only with 1,2-DBP 24 h after the treatment. The hepatic content of glutathione was reduced by 1,2-DBP. Meanwhile, these parameters were increased by 2-BP. The present results suggest that 1,2-DBP in the Solvent 5200 also contributes to the immnunotoxicity, although 2-BP is a major component.

Identification of glutathione conjugates of 1-bromopentane and its hepatotoxicity in female BALB/c mice

“…2-BP and 1,2-DBP significantly elevated serum ALT and AST activity after oral administration of 2-BP at 2000 or 4000 mg/kg, or 1,2-DBP at 300 or 600 mg/kg to mice, as well as reducing hepatic GSH content by 1,2-DBP (Kim et al, 2003). Oral treatment with 1-BP significantly decreased hepatic GSH content and produced GSH conjugates of 1-BP.…”

“…In our previous studies, the depletion of hepatic GSH caused by the formation of GSH conjugate with haloalkanes contributed to increased hepatotoxicity (Kim et al, 2003;Lee et al, 2007a;Lee et al, 2007b). 2-BP and 1,2-DBP significantly elevated serum ALT and AST activity after oral administration of 2-BP at 2000 or 4000 mg/kg, or 1,2-DBP at 300 or 600 mg/kg to mice, as well as reducing hepatic GSH content by 1,2-DBP (Kim et al, 2003).…”

“…GSH conjugation is generally a detoxifying process and hepatic GSH content may be an important factor in certain chemical-induced hepatotoxicity. Particularly, the hepatic content of GSH is reduced by the formation of GSH conjugates with many haloalkanes (Kim et al, 2003;Tornero-Velez et al, 2004;Lee et al, 2007a;Lee et al, 2007b).…”

“…In our previous studies, bromoalkane compounds such as 1-bromopropane (1-BP), 2-bromopropane (2-BP), 1,2-dibromopropane (1,2-DBP), and 1,3-dibromopropane could cause hepatotoxicity and immunotoxicity as well as depletion of GSH content by GSH conjugate formation in mice (Kim et al, 2003;Lee et al, 2005;Lee et al, 2007a;Lee et al, 2007b). Moreover, 1-BPT could be excreted in rat urine as several metabolites, including pentylmercapturic acid derivates (Grasse et al, 1970;Grasse and James, 1972).…”

Hepatotoxic and Immunotoxic Effects produced by 1,3‐Dibromopropane and Its Conjugation with Glutathione in Female BALB/c Mice

“…Mice treated orally with 1-BP showed enhanced hepatotoxicity and immunotoxicity following depletion of GSH in liver and spleen (Lee et al, 2005b). In addition, the hepatotoxicity and immunotoxicity produced by 2-BP and 1,2-DBP were also increased by the formation of conjugates with GSH (Kim et al, 2003;Lee et al, 2005a).…”