Enzyme activities of the hindgut microflora of laboratory animals and man

Rowland, Ian; Mallett, A.K.; Bearne, C.A.; Farthing, M. J. G.

doi:10.3109/00498258609043540

Cited by 59 publications

(23 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because many chemicals induce colon DNA damage in a similar way in mice and rats, this unique azo-induced differential DNA damage might reflect the different metabolism of these dyes between mice and rats. There are marked differences in enzyme activities associated with the hindgut microflora such as caecal azoreductase between rats and mice (Rowland et al, 1986). A species difference in the extent of N-oxidation of azo compounds is also evident between rats and mice (Koh and Gorrod, 1989).…”

Section: Discussionmentioning

confidence: 99%

Differential colon DNA damage induced by azo food additives between rats and mice

et al. 2010

View full text Add to dashboard Cite

-Azo dyes, amaranth, allura red and new coccine, which are currently used as food color additives in Japan, have been reported to cause colon specific DNA damage in mice. To examine species difference in the DNA damage between rats and mice, each of dyes was administered to male mice (1 and 10 mg/kg) and male rats (10, 100 and 1,000 mg/kg) by gavage. Brain, lung, liver, kidney, glandular stomach, colon, urinary bladder and bone marrow were sampled 3 hr (for mice) and 3, 6, 12 and 24 hr (for rats) after the treatment. The alkaline comet assay showed DNA damage in the mouse colon 3 hr after the administration of all of the dyes at 10 mg/kg. In rats, however, none of the dyes damaged DNA. Azo dyes should undergo metabolic reduction in the colon to be adducted to DNA. To determine transit time of the dyes to the colon after their administration, gastric emptying and intestinal transport in mice and rats were examined using brilliant blue FCF (BB) as an indicator. The half times of gastric emptying were 70 and 80 min for mice and rats, respectively; and about 60% of the BB was removed from the stomach 1 hr after the gastric intubation in both mice and rats. BB reached the mouse and rat colon 1 and 3 hr after the administration, respectively. Considering the wide dose range and sampling times well covering the transit time to the colon, rats may be insensitive to these azo dye-induced DNA damage.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential colon DNA damage induced by azo food additives between rats and mice

et al. 2010

View full text Add to dashboard Cite

show abstract

“…For rats, the weight of cecal content was 2.9 g, and for humans, the weight of feces was 110 g (Rowland et al, 1986). The average colonic transit time was 6 hours for rats (de Zwart et al, 1999) and 24 hours for humans (Wilson, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…There can be substantial species differences in specificity and substrate selectivity for drug metabolizing enzymes between rats and humans (Martignoni et al, 2006). Similarly, species differences in gut microbiota (Rowland et al, 1986) make interspecies extrapolations difficult. Germ-free rats have been used to evaluate the role of bacterial microbiota in the metabolism of several compounds, including hesperidin, acetaminophen, and mangiferin (Jin et al, 2010;Lee et al, 2012;Liu et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…In vivo evaluation of gut bacterial metabolism in animals is feasible. However, the limitations of large interspecies differences in microbiota composition and distribution have to be taken into consideration (Rowland et al, 1986;Sousa et al, 2008). Pseudo-germ free (pGF) rats can be created by treatment with broadspectrum antibiotics and have helped in elucidating the role of gut bacteria in the metabolism of drugs (Jin et al, 2010;Lee et al, 2012;Liu et al, 2012;Yoo et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Defining the Role of Gut Bacteria in the Metabolism of Deleobuvir: In Vitro and In Vivo Studies

et al. 2015

View full text Add to dashboard Cite

Deleobuvir is a potent inhibitor of the hepatitis C virus nonstructural protein 5B polymerase. In humans, deleobuvir underwent extensive reduction to form CD 6168. This metabolite was not formed in vitro in aerobic incubations with human liver microsomes or cytosol. Anaerobic incubations of deleobuvir with rat and human fecal homogenates produced CD 6168. Using these in vitro formation rates, a retrospective analysis was conducted to assess whether the fecal formation of CD 6168 could account for the in vivo levels of this metabolite. The formation of CD 6168 was also investigated using a pseudo-germ free (pGF) rat model, in which gut microbiota were largely eradicated by antibiotic treatment. Plasma exposure (area under the curve from 0 to ') of CD 6168 was approximately 9-fold lower in pGF rats (146 6 64 ng·h/ml) compared with control rats (1,312 6 649 ng·h/ml). Similarly, in pGF rats, lower levels of CD 6168 (1.5% of the deleobuvir dose) were excreted in feces compared with control rats (42% of the deleobuvir dose). In agreement with these findings, in pGF rats, approximately all of the deleobuvir dose was excreted as deleobuvir into feces (105% of dose), whereas only 26% of the deleobuvir dose was excreted as deleobuvir in control rats. These differences in plasma and excretion profiles between pGF and control rats confirm the role of gut bacteria in the formation of CD 6168. These results underline the importance of evaluating metabolism by gut bacteria and highlight experimental approaches for nonclinical assessment of bacterial metabolism in drug development.

show abstract

“…Animals are therefore used to study the metabolism and fermentation of NSP (Bu †enstein and Yahar 1991 ; Knusden et al 1991 ;Mascolo et al 1991 ;McIntyre et al 1991 ;Edwards et al 1992). There are di †erences in both the rate of fermentation of NSP and in the mix of short-chain fatty acids (SCFA) produced when animal microÑora is used, compared to humans (Nyman and Asp 1986 ;Rowland et al 1986 ;Rowland and Mallett 1988). Various in vitro methods have been used to simulate conditions in the human colon and colonic microbial population (Miller and Wolin 1981 ;McBurney and Thompson 1987 ;Lenge-Peschlow 1989).…”

Section: Introductionmentioning

confidence: 99%

A Consistent Inoculum System to Study the Fermentation of Non-starch Polysaccharides

Stevenson

Buchanan

Eastwood

1997

J. Sci. Food Agric.

View full text Add to dashboard Cite

Enzyme activities of the hindgut microflora of laboratory animals and man

Cited by 59 publications

References 11 publications

Differential colon DNA damage induced by azo food additives between rats and mice

Differential colon DNA damage induced by azo food additives between rats and mice

Defining the Role of Gut Bacteria in the Metabolism of Deleobuvir: In Vitro and In Vivo Studies

A Consistent Inoculum System to Study the Fermentation of Non-starch Polysaccharides

Contact Info

Product

Resources

About