Role of glutathione conjugation in the hepatotoxicity and immunotoxicity induced by 1‐bromopropane in female BALB/c mice

Abstract

1-Bromopropane (1-BP) is used as a cleaning agent or adhesive solvent in the workplace. In the present study, the hepatotoxic and immunotoxic effects of 1-bromopropane and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. The animals were treated orally with 200, 500 and 1000 mg kg(-1) of 1-BP in corn oil for a dose response study or treated orally with 1000 mg kg(-1) of 1-BP for 6, 12, 24 and 48 h for a time course study. The hepatic and splenic contents of GSH were significantly decreased by 1-BP in a dose-dependent manner. S-propyl GSH was identified in livers following treatment with 1-BP by liquid chromatography-electrospray ionization tandem mass spectrometry. When the production of conjugates from 1-BP was investigated in livers following oral treatment with 1000 mg kg(-1) of 1-BP for 6, 12, 24 and 48 h, the GSH conjugates were detected maximally 6 h after treatment. Treatment of mice with 1-BP increased the serum activity of alanine aminotransferase dose-dependently. The oral 1-BP treatment significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular IL-2 in response to Con A in a dose-dependent manner. The present results suggested that 1-BP could cause hepatotoxicity and immunotoxicity as well as depletion of GSH content due to the formation of GSH conjugates.

Effect of five acetylcholinesterase reactivators on tabun‐intoxicated rats: induction of oxidative stress versus reactivation efficacy

“…The increase of detected current due to oxidative stress induced by the reactivator (see following text) was proportional to elevated glutathione concentration up to 50 mM. It displayed a predictable shift (Langstom et al, 2008;Lee et al, 2007). Glutathione was selected as a representative antioxidant playing an important role in defense mechanisms (Qin et al, 2008); on the other hand, diff erent groups of antioxidants have been found (Rathore et al, 1998).…”

NIOSH skin notation (SK) profile: 1-bromopropane [CAS No. 106-94-5].

“…Lee et al [2005Lee et al [ , 2007 treated mice with a single dose of 1-BP at levels of 200, 500, and 1,000 mg/kg via the oral route. At 500-and 1000-mg/kg treatment levels, the authors reported a significant increase in relative liver weight and changes in liver enzyme levels [Lee et al 2005[Lee et al , 2007.…”

“…Lee et al [2005Lee et al [ , 2007 treated mice with a single dose of 1-BP at levels of 200, 500, and 1,000 mg/kg via the oral route. At 500-and 1000-mg/kg treatment levels, the authors reported a significant increase in relative liver weight and changes in liver enzyme levels [Lee et al 2005[Lee et al , 2007. In another investigation, Zhao et al [1999] treated rats with daily injections of 1-BP at treatment levels of 3.7 millimoles (mmol)/kg (corresponding to 455 mg/kg) and 11.0 mmol/kg (corresponding to 1,353 mg/kg) for 20 days.…”

1‐Brompropan [MAK Value Documentation in German language, 2011]

“…Dies bewirkte bei 1000 mg/kg KG signifikant verringerte GSH-Gehalte in Leber und Milz, erhöhte Bildung von GSH-Konjugaten, insbesondere in der Leber,e rhöhte Aktivitäten der Alanin-und Aspartat-Aminotransferase, erhöhte Malondialdehyd-Bildung in der Leber sowie erhöhte relative Lebergewichte. Die Autoren führen die Hepatotoxizität auf die GSH-Depletion aufgrund der Bildung von GSH-Konjugaten zurück (Lee et al 2005(Lee et al , 2007. Andererseits kann die deutlich stärkere Empfindlichkeit von Mäusen im Ve rgleich zu Ratten auf deren höheren Spiegel an CYP2E1 beruhen ).…”

“…Die Autorenvermuten, wiebei derHepatotoxizität,die Bildungvon GSH-Konjugaten unddie dadurchv erringerten zellulären GSH-Spiegeli nd er Milz alsm öglicheU rsache deri mmunsuppressivenWirkung.Sokonntegezeigt werden,dassdie intrazelluläre GSH-Depletion dieE ffektor-Phased er zytotoxischenT -Zell-Immunantwort undI L-2-abhängige Funktionen hemmt, dieStimulation derDNA-Synthesevon Lymphozyten beeinträchtigt unddas IL-2-abhängige T-Zell-Wachstumhemmt (Lee et al 2007). In einer In-vitro-Untersuchung an Maus-Makrophagen war ab 1 μM1-Brompropan die Produktion von NO, TNF-α,IL-1β und IL-6 signifikant erhöht (Han et al 2008).…”