A possible role of metabolism by intestinal bacteria in arbutin-induced toxicity was investigated in mammalian cell cultures. Following an incubation of arbutin with intestinal bacteria, either Bifidobacterium longum HY81 or Bifidobacterium adolescentis, for 24 h, its aglycone hydroquinone could be produced and detected in the bacterial culture media. The bacterial growth was not affected up to 10 mM arbutin in the culture medium. When the toxicity of bacteria cultured medium with arbutin was tested in the HepG2 cell lines, the medium with arbutin was more toxic than either parent arbutin only or bacteria cultured medium without arbutin, indicating that metabolic activation might be required in arbutin-induced toxicity. In addition, bacteria cultured medium with arbutin could suppress LPS and ConA mitogenicity in splenocyte cultures prepared from normal mice. The results indicate that the present toxicity testing system might be applied for assessing the possible role of metabolism by intestinal bacteria in certain chemical-induced toxicity in mammalian cell cultures.
A possible role of metabolism in 1-bromopropane (1-BP)-induced hepatotoxicity was investigated in male ICR mice. The depletion of glutathione (GSH) by formation of GSH conjugates was associated with increased hepatotoxicity in 1-BP-treated mice. The formation of S-propyl and 2-hydroxypropyl GSH conjugates were identified in the liver following 1-BP treatment. In addition, the formation of reactive metabolites of 1-BP by certain cytochrome P-450 (CYP) may be involved in 1-BP-induced hepatotoxicity. The decreased content of hepatic GSH produced by 1-BP was associated not only with increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) but also with elevated levels of hepatic thiobarbituric acid-reactive substance (TBARS) in mice where metabolic enzymes were induced by pretreatment with phenobarbital. In addition, the hepatotoxicity induced by 1-BP was prevented by pretreatment with SKF-525A. Taken together, the formation of reactive metabolites by CYP and depletion of GSH may play important roles in hepatotoxicity induced by 1-BP.
Role of metabolism by intestinal bacteria in arbutin-induced immunotoxicity was investigated in splenocyte cultures. Following an incubation of arbutin with 5 different intestinal bacteria for 24 hr, its aglycone hydroquinone could be produced and detected in the bacterial culture media with different amounts. Toxic effects of activated arbutin by intestinal bacteria on lymphoproliferative response were tested in splenocyte cultures from normal mice. Lipopolysaccharide and concanavalin A were used as mitogens for B- and T-cells, respectively. When bacteria cultured medium with arbutin was treated into the splenocytes for 3 days, the medium cultured with bacteria producing large amounts of hydroquinone induced suppression of lymphoproliferative responses, indicating that metabolic activation by intestinal bacteria might be required in arbutin-induced toxicity. The results indicated that the present testing system might be applied for determining the possible role of metabolism by intestinal bacteria in certain chemical-induced immunotoxicity in animal cell cultures.
Hepatotoxic and immunotoxic effects of 1-bromohexane (1-BH) and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. The animals were treated once orally with 1-BH at 500, 1000, and 2000 mg/kg in corn oil for a dose-response study or treated orally with 1-BH at 2000 mg/kg for 6, 12, 24, and 48 hr for a time-course study. Treatment with 1-BH increased serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) dose dependently. The hepatic contents of thiobarbituric acid reactive substances were significantly increased at 2000 mg/kg of 1-BH from 12 to 24 hr after the treatment. Oral 1-BH at 2000 mg/kg significantly suppressed production of splenic intracellular interleukin (IL)-2 in response to concanavalin A. Following treatment with 1-BH, three GSH conjugates such as S-hexyl GSH, S-hexyl cysteine, and hydroxyhexyl mercapturic acid were identified in livers by liquid chromatography-electrospray ionization tandem mass spectrometry. The hepatic contents of GSH were maximally decreased 6 hr after treatment with 1-BH. GSH conjugates were also detected maximally in livers 6 hr after treatment. These results suggest that 1-BH could cause hepatotoxicity and immunotoxicity as well as depletion of GSH content due to the formation of GSH conjugates with 1-BH in female BALB/c mice.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.