Effects of Kramecyne on <scp>LPS</scp> Induced Chronic Inflammation and Gastric Ulcers

Alonso-Castro, Ángel Josabad; Pérez‐Ramos, Julia; Sánchez-Mendoza, Ernesto; Pérez-González, Cuaúhtemoc; Pérez-Gutiérrez, Salúd

doi:10.1002/ddr.21254

Cited by 3 publications

(1 citation statement)

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“…It is composed of six monomers of epoxide with the formula C 30 H 8 O 4 (Pérez et al, 2012). This compound has not only demonstrated activity similar to Krameria cytisoides Cav , but also produced other beneficial effects according to pharmacological studies on animals (Sánchez et al, 2013, Alonso et al, 2015a, Alonso et al, 2015b). An in vivo experiment reported that at a dose of 250 μg/mL in a culture of macrophages, this polymer induced a low level of toxicity, evidenced by an LD 50 greater than 5000 mg/kg (Pérez et al, 2012), and a low level of cytotoxicity (Sánchez et al, 2013).…”

Section: Introductionmentioning

confidence: 95%

Evaluation of teratogenicity and genotoxicity induced by kramecyne (KACY)

Cristóbal-Luna

Paniagua-Castro

Escalona-Cardoso

et al. 2018

Saudi Pharmaceutical Journal

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Kramecyne (KACY), a polymer isolated from , has anti-inflammatory, anti-nociceptive, anti-arthritic and anti-ulcerogenic properties. As a part of standard preclinical safety tests, the present study sought to determine potential developmental toxicity (in female rats) and genotoxicity (in male mice) of KACY. Pregnant female rats were divided into six groups: the negative control (vehicle), the positive control (250 mg/kg of acetylsalicylic acid (ASA)), and four experimental groups (50, 250, 500 and 1000 mg/kg of KACY). To evaluate genotoxicity by micronuclei (MN) and sister chromatid exchange (SCE) tests, male mice were divided into five groups: the negative control (vehicle), the positive control (1.5 and 2.5 mg/kg of doxorubicin for MN and SCE, respectively), and three experimental groups (50, 500 and 1000 mg/kg of KACY). All treatments were administered by oral gavage. A slight maternal toxicity was evidenced by lower weight gain for rats receiving 500 and 1000 mg/kg of KACY, but no fetal malformations were found. However, there were less live fetuses/litter and greater post-implantation loss/litter at these two doses. Manifestations of developmental toxicity were limited to a higher rate of skeletal alterations. The MN tests did not evidence genotoxicity or cytotoxicity. KACY caused a slightly but significantly increased frequency of SCE. Although KACY-treated rats had skeletal alterations, these apparently were not caused by a mechanism of genotoxicity. Furthermore, the same administration in adult male mice did not produce genotoxicity. Hence, KACY herein proved to be safe for rats during the period of organogenesis.

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Section: Introductionmentioning

confidence: 95%

Evaluation of teratogenicity and genotoxicity induced by kramecyne (KACY)

Cristóbal-Luna

Paniagua-Castro

Escalona-Cardoso

et al. 2018

Saudi Pharmaceutical Journal

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Induction of Chronic Subclinical Systemic Inflammation in Sprague–Dawley Rats Stimulated by Intermittent Bolus Injection of Lipopolysaccharide

Ranneh

Akim

Hamid

et al. 2019

Arch. Immunol. Ther. Exp.

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Induction of chronic subclinical systemic inflammation in sprague-dawley rats stimulated by intermittent bolus injection of lipopolysaccharide ABSTRACT Chronic subclinical systemic inflammation has a key role in stimulating several chronic conditions associated with cardiovascular diseases, cancer, rheumatoid arthritis, diabetes, and neurodegenerative diseases. Hence, developing in vivo models of chronic subclinical systemic inflammation are essential to the study of the pathophysiology and to measure the immunomodulatory agents involved. Male Sprague-Dawley rats were subjected to intraperitoneal, intermittent injection with saline, or lipopolysaccharide (LPS) (0.5, 1, 2 mg/kg) thrice a week for 30 days. Hematological, biochemical, and inflammatory mediators were measured at different timepoints and at the end of the study. The hearts, lungs, kidneys, and livers were harvested for histological evaluation. Significant elevation in peripheral blood leukocyte includes neutrophils, monocytes, and lymphocytes, as well as the neutrophils-tolymphocyte ratio. The pro-inflammatory mediator levels [C-reactive protein, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8] along with the biochemical profile (alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, creatinine, and urea) were increased significantly (P < 0.05) and increased the expression of monocyte chemoattractant protein-1 and TNF-β. The histopathological changes of heart, lung, kidney, and liver tissues revealed degeneration, cellular infiltration of leukocyte in the inflammatory foci and interstitial space, edema, early signs of fibrosis, apoptosis, and necrosis. In conclusion, these results indicate that intermittent exposure to LPS produces chronic subclinical systemic inflammation in multiple organs leading to chronic conditions and supports this model to be a useful preclinical tool for developing immunotherapeutic agents that could prevent, or reduce, chronic inflammatory diseases associated with, or without, bacterial translocation.

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