Isoquinolone alkaloids mitigate microscopic digestive tract lesions induced by sub-acute ruminal acidosis (SARA) in feedlot cattle

Abstract

Feedlot cattle is submitted to a diet rich in energy and reduced in fibres that induces the sub-acute ruminal acidosis (SARA) with its lesions and clinical signs. Recent studies have demonstrated some amelioration of this condition by the use of isoquinolone alkaloids found in Macleaya cordata (Papaveraceae) such as Sanguinarine and Chelerythrine. These compounds have demonstrated antimicrobial, anti-inflammatory and immune-modulatory effects in both humans and animals The aim on this study, using histopathology and a score system, was to evaluate the differences between a non-treated and a treated group feed with these alkaloids, present in trade preparation Sangrovit-RS® as a source of sanguinarine (SG), chelerythrine (CH) and protropine (PA) standardized to 0.15% w/w SG, using feedlot cattle under a high-grain diet as an inflammatory model for gastrointestinal system. The samples of forestomachs were evaluated and graded using scores ranging from zero (0) to three (3) obtained at light-microscopic fields of 400X. Parameters such as inflammation, hydropic degeneration, hyperkeratosis, and vesicle formation were accessed in the different layers of the tissues, considering the severity and dispersion of the microscopic lesions. The soft tissues such as the abomasum, small intestine, cecum and colon had their total amount of inflammatory cells counted at light-microscopic fields of 200X. The rumen of the SG-CH-PRO-treated group showed a significant reduction in the epithelial hydropic degeneration scores (p ≤ 0.001) and lamina propria inflammation (p ≤ 0.001).The reticulum had a similar reduction in scores of epithelial (p ≤ 0.002) and stratum corneum hydropic degeneration (p ≤ 0.001), hyperkeratosis (p ≤ 0.002) and inflammation in lamina propria (p ≤ 0.001) and epithelium (p ≤ 0.002). The omasum had no significant differences. All non-keratinized tissues, except for ileum, had a significant decrease (p ≤ 0.001) in the total counting of inflammatory cells. In this trial, the feedlot cattle feed with high grain diet and treated with isoquinolone alkaloids expressed lesions that indicate ameliorations and worsening’s. Ameliorating effects of the alkaloids were better demonstrated in tissues with reduced or no corneal layer in the mucosa and in the absence of a lipopolysaccharides rich acidic environment reinforcing the notion of the topic action, the dependence of the media pH and the time of exposure modulating the pharmacological mechanisms of these alkaloids. The observed cytolytic (oncolysis) effect in epithelial forestomachs cells under low pH values, worsening the osmotic status, should be considered before clinical applications.