Effect of glutathione status on covalent binding and pneumotoxicity of 3-methylindole in goats

Nocerini, Mark R.; Carlson, James R.; Breeze, R. G.

doi:10.1016/0024-3205(83)90137-6

Cited by 34 publications

(14 citation statements)

References 24 publications

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“…Since hepatic GSH levels are considerably higher than pulmonary GSH levels, the high GSH concentrations in hepatic tissues might play a role in the defense of the liver, but, obviously, high hepatic GSH levels do not prevent hepatic covalent binding of 3MI. Pulmonary GSH modulation (30) has demonstrated that 3MI-induced pneumotoxicity can be increased or decreased by depletion with diethyl maleate or supplementation with cysteine of pulmonary GSH levels. L-Buthionine (S,R)-sulfoximine (BSO) is a selective inhibitor of GSH synthesis (33) and also selectively depletes hepatic GSH (34) without sig- OControl GSH levels were as follows: liver, 8.4 pmol/g; lung, 1.9 pmol/g; and kidney, 0.44 pmollg.…”

Section: Glutathione Modulation Of Organ Selectivitymentioning

confidence: 99%

Mechanisms of 3-methylindole pneumotoxicity

Yost¹

1989

Chem. Res. Toxicol.

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Section: Glutathione Modulation Of Organ Selectivitymentioning

confidence: 99%

Mechanisms of 3-methylindole pneumotoxicity

Yost¹

1989

Chem. Res. Toxicol.

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“…A comparison of in vivo ruminal 3MI levels in individual cows (data not shown) suggests that some cows are more resistant to this disease than others. Because the 3MI concentration to cause death differs, other factors such as genetics, nutritional status or metabolic dif- (Nocerini et al, 1983) may be involved.…”

Section: Resultsmentioning

confidence: 99%

Duration of Inhibition of 3-Methylindole Production by Monensin3

Honeyfield

Carlson

Nocerini

et al. 1985

Journal of Animal Science

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A series of in vitro and in vivo trials was conducted to determine if continuous monensin feeding for up to 56 d would reduce ruminal conversion of L-tryptophan (TRP) to 3-methylindole (3MI). Fourteen mature beef cows were adapted to a maintenance diet for 3 wk. In trial I, the sampling time to optimize 3MI production was determined. Trials II through IV were to determine the duration of efficacy of monensin on reducing 3MI concentrations in vitro and in vivo. During trials II, III and IV one-half of the cows were fed 200 mg monensin X head-1 X d-1 for 21, 36 and 55 d, respectively, while the remaining cows served as controls. All cows were fed the control diet for 21 d between each trial. Volatile fatty acid (VFA) concentrations and in vitro conversion of TRP to 3MI were determined in ruminal fluid samples collected during trials I through IV. On d 28 of trial IV, all cows were given an oral dose of .35 g TRP/kg of body weight to induce acute bovine pulmonary edema and emphysema (ABPE). Ruminal concentrations of 3MI and indole were measured at intervals for 96 h. Results of trial I demonstrated that ruminal fluid collected 15 h postfeeding produced the highest in vitro conversion of TRP to 3MI. Therefore, ruminal fluid samples were collected at that time in trials II, III and IV. In vitro conversion of TRP to 3MI was lower (P less than .01) in samples from monensin-treated cows (12.1%) compared with controls (25.6%). Monensin reduced 3MI production for 55 d, the longest time tested in these experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…41 Glutathione depletion results in increased lung damage in mice and goats. 38 The metabolism of 3MI has been studied extensively in goats and less so in other species. However, the relative importance of pulmonary and extrapulmonary metabolism is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Chemical Modulation of 3-Methylindole Toxicosis in Mice: Effect on Bronchiolar and Olfactory Mucosal Injury

1986

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Abstract. C57BW6N mice were treated to induce tolerance, to modulate the mixed function oxidase system or to deplete glutathione (GSH) before injection with 400 mg 3-methylindole (3MI)/kg. Effect of pretreatment was determined by histologic comparison of pulmonary and nasal lesions 24 hours after 3MI. p-Naphthoflavone and 3MI pretreatment significantly decreased 3MI-induced bronchiolar epithelial damage in male and female mice, while phenobarbital protection was significant only in female mice. Only p-naphthoflavone decreased nasal olfactory epithelial damage. Pretreatment with piperonyl butoxide, SKF 525-A, or a-naphthoflavone had no significant effect on development of lesions. Diethylmaleate pretreatment significantly increased mortality and bronchiolar damage in both sexes. Significant differences between male and female mice were not detected in any group. The results suggest that pretreatment with low doses of 3MI or induction of cytochrome P-448 or P-450 protects against 3MI toxicosis while GSH depletion increases mortality and pulmonary lesions.3-Methylindole (3MI) is one cause of acute bovine pulmonary edema and interstitial emphysema (ABPE). 16,24,46 Pathologic features of ABPE are pulmonary congestion and edema, alveolar hyaline membranes, interstitial emphysema, and hyperplasia of type I1 pneumocytes.14 These lesions are induced in cattle, sheep, or goats by oral or intravenous administration of 3MI.Destruction of nonciliated bronchiolar epithelial (Clara) cells accompanies alveolar damage in goat^^,^' and sheep,Io but not cattle.' In and C57BL mice,43 3MI selectively damages Clara cells and results in bronchiolitis without alveolar edema.Lesions produced by 3MI in mice43 resemble those induced by toxins which are metabolized by a cytochrome P-450-dependent mixed function oxidase (MFO) r e a c t i~n .~,~' .~~ Alteration of 3MI-induced pulmonary lesions in goats by MFO modulation suggests that a 3MI metabolite rather than the parent compound causes the pulmonary lesions." However, MFO induction and inhibition has variable effects on 3MI toxicosis in goats.11,34Tissue glutathione (GSH) concentration is inversely correlated with the severity of 3MI-induced pulmonary lesions in goat^.^^,^^ 3-Methylindole generates a free radical in caprine pulmonary micro some^,^^ and it has been suggested that GSH protects against 3MI toxicosis by conjugation with this free radical.I6Cytochrome P-450-dependent MFO activity has been documented in the mouse 1ung3,7,8J9 and nasal cavity23 and murine respiratory toxicosis can be altered by manipulation of the MFO system.22 In the present study, 3MI toxicosis in mice was studied to determine if low doses of 3MI would induce tolerance to 3M1, to determine the role of the MFO system in the development of bronchiolar and olfactory epithelial damage, to determine the effect of GSH depletion on development of bronchiolar and olfactory epithelial damage and to determine the effect of gender on chemical modulation of 3MI toxicosis.

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Effect of glutathione status on covalent binding and pneumotoxicity of 3-methylindole in goats

Cited by 34 publications

References 24 publications

Mechanisms of 3-methylindole pneumotoxicity

Mechanisms of 3-methylindole pneumotoxicity

Duration of Inhibition of 3-Methylindole Production by Monensin3

Chemical Modulation of 3-Methylindole Toxicosis in Mice: Effect on Bronchiolar and Olfactory Mucosal Injury

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