Association of 3-methyleneindolenine, a toxic metabolite of 3-methylindole, with acute interstitial pneumonia in feedlot cattle

Loneragan, Guy H.; Gould, Douglas; Mason, Gary L.; Garry, Franklyn B.; Yost, Garold S.; Lanza, Diane L.; Miles, D. G.; Hoffman, Bruce W.; Mills, Leon J.

doi:10.2460/ajvr.2001.62.1525

Cited by 43 publications

(36 citation statements)

References 22 publications

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“…2,3,11 Heifers are often disproportionately affected, and in 1 report the odds of an animal with AIP being a heifer were 3.1 times greater than male cattle. 12 In a survey of feedlots to determine risk factors for AIP, however, feedlots where 50% to 75% of placements were heifers did not always report having cases of AIP. 10 Thus, in feedlots where AIP occurs, heifers may be disproportionately affected, but feedlots placing large numbers of heifers do not always see AIP.…”

Section: Epidemiology and Risk Factorsmentioning

confidence: 95%

Feedlot Acute Interstitial Pneumonia

Woolums

2015

Veterinary Clinics of North America: Food Animal Practice

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Section: Epidemiology and Risk Factorsmentioning

confidence: 95%

Feedlot Acute Interstitial Pneumonia

Woolums

2015

Veterinary Clinics of North America: Food Animal Practice

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“…Numerous examples of substrate dehydrogenation reactions exist in the literature, including the formation of alkenes from fatty acids (Guan et al, 1998;Haining et al, 1999), a toxic alkene of valproic acid (Rettie et al, 1987;Rettie et al, 1988;Kassahun and Abbott, 1993;Rettie et al, 1995;Sadeque et al, 1997), ezlopitant (Obach, 2001), and reactive eneimine metabolites of the leukotriene receptor antagonist zafirlukast (Kassahun et al, 2005) and of the pneumotoxicant 3-methylindole (Adams et al, 1987;Yost, 1989;Ruangyuttikarn et al, 1991;Skiles and Yost, 1996;Skordos et al, 1998a;Skordos et al, 1998b;Loneragan et al, 2001). Interestingly, many dehydrogenated products of xenobiotics exhibit unique toxicity that is not observed for hydroxylated products.…”

Section: Alkyl Dehydrogenation and Oxygenation Of Capsaicinoids By P4mentioning

confidence: 99%

Metabolism of Capsaicinoids by P450 Enzymes: A Review of Recent Findings on Reaction Mechanisms, Bio-Activation, and Detoxification Processes

Reilly

Yost

2006

Drug Metabolism Reviews

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Capsaicinoids are botanical irritants present in chili peppers. Chili pepper extracts and capsaicinoids are common dietary constituents and important pharmaceutical agents. Use of these substances in modern consumer products and medicinal preparations occurs worldwide. Capsaicinoids are the principals of pepper spray self-defense weapons and several over-the-counter pain treatments as well as the active component of many dietary supplements. Capsaicinoids interact with the capsaicin receptor (a.k.a., VR1 or TRPV1) to produce acute pain and cough as well as long-term analgesia. Capsaicinoids are also toxic to many cells via TRPV1-dependent and independent mechanisms. Chemical modifications to capsaicinoids by P450 enzymes decreases their potency at TRPV1 and reduces the pharmacological and toxicological phenomena associated with TRPV1 stimulation. Metabolism of capsaicinoids by P450 enzymes also produces reactive electrophiles capable of modifying biological macromolecules. This review highlights data describing specific mechanisms by which P450 enzymes convert the capsaicinoids to novel products and explores the relationship between capsaicinoid metabolism and its effects on capsaicinoid pharmacology and toxicology. CAPSAICINOID PHARMACOLOGY, TOXICOLOGY, AND HUMAN EXPOSURE SOURCESThe capsaicinoids are a family of natural products isolated from the fruits of "hot" peppers (Govindarajan, 1985;Govindarajan and Sathyanarayana, 1991). These substances produce the characteristic sensations associated with the ingestion of spicy food. Capsaicinoids elicit multiple characteristic pharmacological responses that include severe irritation, inflammation, erythema, and transient hyper-and hypoalgesia at exposed sites; capsaicinoids are particularly irritating to the eyes, skin, nose, tongue, and respiratory tract, where large numbers of sensory nerve fibers (C-and Aδ-) terminate that express high quantities of the capsaicin receptor (i.e., VR1 or TRPV1). TRPV1 has been cloned and its pharmacological properties and physiological roles characterized (Caterina et al., 1997). TRPV1 is a calcium channel that, when activated by capsaicinoids, produces the characteristic sensations previously described and causes toxicity in many mammalian cell types (Lee et al., 2000;Maccarrone et al., 2000;Macho et al., 2000;Surh, 2002;Reilly et al., 2003b;Agopyan et al., 2004;Johansen et al., 2006). Several excellent and comprehensive reviews dedicated to TRPV1 have been published (Szallasi and Blumberg, 1999;Caterina and Julius, 2001).There are numerous naturally occurring capsaicinoid analogs (Kozukue et al., 2005;Thompson et al., 2005a;Thompson et al., 2005b) dihydrocapsaicin, nordihydrocapsaicin, nonivamide, homocapsaicin, and homodihydrocapsaicin (Reilly et al., 2001a;Reilly et al., 2001b). The chemical structures of the major capsaicinoid analogs are depicted in Fig. 1. All analogs have the capacity to bind to and activate TRPV1, albeit with different potencies depending primarily upon the alkyl chain structure (Pyman, 1925;Hayes...

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“…Feedlot diets typically do not contain high levels of highly available protein and the amino acid Ltryptophan that can be present in lush forages. However, increased levels of breakdown products of L-tryptophan have been found in the lungs of feedlot cattle with AIP (Loneragan et al, 2001a). In this study, there were no differences in feed intake patterns between pens that experienced a case of AIP and those that did not.…”

Section: Discussionmentioning

confidence: 42%

“…Hydrogen sulfide has been shown to cause lung lesions in rats (Lopez et al, 1987;Prior et al, 1988). Also in grazing cattle, AIP been tied to the L-tryptophan content of lush forages and the resulting 3-methylindole metabolism in the rumen (Loneragan et al, 2001a). This study was conducted to clinically observe ante-mortem cases of cattle suffering from AIP compared to their nonaffected pen cohorts and examine management conditions or cattle feeding behavior that might lead to AIP incidence in cattle feeding facilities.…”

Section: Introductionmentioning

confidence: 99%

Pathologies of Acute Interstitial Pneumonia in Feedlot Cattle

Valles¹,

Apley²,

Reinhardt³

et al. 2016

American Journal of Animal and Veterinary Sciences

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Acute Interstitial Pneumonia (AIP) is a costly issue that affects feedlot cattle. Research has yet to elucidate the etiology of AIP; therefore a case-control study was conducted to evaluate possible management and physiological factors that contribute to AIP in feedlot cattle. The experiment was conducted during the summer of 2011 in a commercial feedyard in Kansas. Animals exhibiting clinical signs of AIP and a control animal from the same pen were selected for ante-mortem examination. Post-mortem AIP cases were also selected for additional examination. Ante-mortem measurements included rumen gas cap hydrogen sulfide and pH, rectal temperature and body weight. Post-mortem examination added histological examination of lung tissue. Rectal temperature was greater in the AIP cattle (40.6±0.16°C) than controls (39.7±0.16°C; p<0.001). Body weight (499±56 Vs. 506±60 kg), hydrogen sulfide (136±133 vs. 269.8±311 ppm) and rumen pH (6.4±0.5 Vs. 6.2±0.6) were similar between AIP and control cattle (p>0.10). Post-mortem rumen pH values were 6.3±0.4 and 5.7±0.6 for AIP and control cattle, respectively. Histological evaluation of lung samples showed that bronchiolitis was present in about 90% of the cattle affected with AIP. About 75% of the cattle with AIP also had bronchopneumonia. No relationships between feed intake patterns, or serum amylase or lipase levels were noted between treatments (p>0.20). This study generally confirms that AIP tends to occur more in heifers relative to steers, occurs in cattle at heavier weights or later in the feeding period and tends to be associated pathologically with bronchio` litis and bronchopneumonia. The lack of differences in rumen measures and the feed intake data between AIP and control cattle suggest that feed intake patterns and rumen fermentation may not impact AIP in feedlot cattle and that it may be more directly related to bronchiolitis/bronchopneumonia due to chronic irritation or infection.

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Association of 3-methyleneindolenine, a toxic metabolite of 3-methylindole, with acute interstitial pneumonia in feedlot cattle

Abstract: Increased pulmonary production of 3MEIN may be an important etiologic factor in feedlot-associated AIP.

Cited by 43 publications

References 22 publications

Feedlot Acute Interstitial Pneumonia

Feedlot Acute Interstitial Pneumonia

Metabolism of Capsaicinoids by P450 Enzymes: A Review of Recent Findings on Reaction Mechanisms, Bio-Activation, and Detoxification Processes

Pathologies of Acute Interstitial Pneumonia in Feedlot Cattle

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