Effects of antibacterial agents on in vitro ovine ruminal biotransformation of the hepatotoxic pyrrolizidine alkaloid jacobine

Abstract

Ingestion of pyrrolizidine alkaloids, naturally occurring plant toxins, causes illness and death in a number of animal species. Senecio jacobaea pyrrolizidine alkaloids cause significant economic losses due to livestock poisoning, particularly in the Pacific Northwest. Some sheep are resistant to pyrrolizidine alkaloid poisoning, because ovine ruminal biotransformation detoxifies free pyrrolizidine alkaloids in digesta. Antibacterial agents modify ruminal fermentation. Pretreatment with antibacterial agents may account for some animal variability in resistance to pyrrolizidine alkaloid toxicosis, and antibacterial agents can also be used for characterizing ruminal pyrrolizidine alkaloid-biotransforming microflora. The objective of this study was to evaluate the effects of antibacterial agents on biotransformation of a predominant S. jacobaea pyrrolizidine alkaloid, jacobine, in ovine ruminal contents. Ovine ruminal jacobine biotransformation was tested in vitro with 20 independent antibacterial agents. Low amounts of rifampin and erythromycin prevented jacobine biotransformation. Chlortetracycline, lasalocid, monensin, penicillin G, and tetracycline were slightly less effective at inhibiting jacobine biotransformation. Bacitracin, crystal violet, kanamycin, and neomycin were moderately inhibitory against jacobine biotransformation. Brilliant green, chloramphenicol, gramicidin, nalidixic acid, polymyxin B SO4, sodium azide, streptomycin, sulfisoxazole, and vancomycin had little to no effect on jacobine biotransformation. The antibiotics that were most effective at inhibiting biotransformation were those that are active against gram-positive bacteria. Therefore, gram-positive bacteria are most likely critical members of the jacobine-biotransforming consortia.

Scientific Opinion on Pyrrolizidine alkaloids in food and feed

“…In 1992 these early studies were followed by a number of publications from Oregon State University (College of Veterinary Medicine). These showed that gram-positive bacteria were most likely critical members for the degradation of jacobine in the rumen of sheep (Wachenheim et al, 1992a), and that when measuring in vitro degradation of Jacobaea vulgaris PAs in bovine (cattle), ovine (sheep), and caprine (goat) rumen contents average rates of around 3, 19 and 26 micrograms/ml per hour, respectively were found. The rumen contents used were from animals that had not recently been exposed to PAs.…”

“…Beside the already described pathways, PA detoxification mediated by bacterial flora in the rumen may be an important contribution to the observed resistance of sheep to PA toxicity (Wachenheim et al, 1992a;Anjos et al, 2010), but evidently not occurring to the same extent in other more susceptible ruminants such as cattle (Cheeke, 1988;Wachenheim et al, 1992b) or in horses (Cheeke, 1988). Further details are given in Section 7.4.…”

Toxin Degradation by Rumen Microorganisms: A Review

“…Clinical symptoms of ruminant PA intoxication include loss of appetite, diarrhoea and depression [ 28 ]. Livestock losses were reported in the United States due to livestock grazing PA containing plants of Senecio jacobaea (tansy ragwort) [ 29 ] while PA intoxication of poultry, cattle, horses and pigs in Australia has identified PA containing plants Heliotropium europaeum (European heliotrope) and Echium plantagineum (Paterson’s curse) to be responsible [ 167 , 168 , 169 , 170 , 171 ]. Calves fed with S. jacobaea in doses of 1.3 kg/day (3 mg/kg bodyweight (bw) PA) resulted in megalocytosis after 182 days [ 32 ].…”

Metabolism-mediated cytotoxicity and genotoxicity of pyrrolizidine alkaloids

“…Consistently, rabbits with high activity of N-glucuronidation are resistant to PA poisoning (Mattocks 1986), while rats, mice, and dogs with negligible N-glucuronidation activity are susceptible to PA toxicity (Huan et al 1998b). Apart from the species variance of PA intoxication mediated by hepatic enzymes, ruminal microbiota has been suggested as an important contributor for PA detoxification in sheep, while other ruminants such as cattle and horses are susceptible to PA intoxication (Anjos et al 2010;Cheeke 1988;Wachenheim et al 1992). Further studies are needed to unravel the functional roles of gut flora in PA metabolism.…”