β-Adrenoceptor Agonist Clenbuterol Down-Regulates Matrix Metalloproteinase (MMP-9) and Results in an Impairment of Collagen Turnover in Mice Left Ventricle

Fiévez

European Journal of Pharmacology

et al. 2010

The anti-inflammatory properties of inhaled formoterol and ipratropium bromide, alone or in combination, were investigated in a rat model of chronic pulmonary inflammation with airspace enlargement induced by cadmium inhalation. At the end of the protocol, cadmium-induced increase of airway resistance was prevented by formoterol (4 mg/30 ml) or ipratropium (0.20 mg/20 ml). Formoterol elicited a significant decrease in total cell and neutrophil counts in bronchoalveolar lavage fluid as well as on the activity of gelatinase B (MMP-9), an enzyme strongly expressed in alveolar macrophages and epithelial cells. Additionally, a significant attenuation of the lung lesions characterized by inflammatory cell infiltration within the alveoli and the interstitium and a decrease in mean linear intercept were observed. Although ipratropium alone had no effects on the cadmium-induced pulmonary inflammation and emphysema, its combination with an inefficient concentration of formoterol (1 mg/30 ml) showed a synergistic inhibitory effect on neutrophil and total cell counts as well as on the mean linear intercept associated with a synergistic inhibition on the MMP-9 activity. Gelatinase A (MMP-2) activity was not influenced by drug pretreatments. Neither macrophage metalloelastase (MMP-12) activity nor levels of cytokines IL-1β, TNF-α and GM-CSF in bronchoalveolar lavage fluid were modified in rats chronically exposed to cadmium. No desensitization of β 2 -adrenoceptors or cholinergic receptors on airway smooth muscles and inflammatory cells during the protocol was observed. In conclusion, formoterol alone or combined with ipratropium bromide partially protects the lungs against the chronic inflammation and airspace enlargement by reducing neutrophilic infiltration possibly via the inhibition of MMP-9 activity.

Section: Discussionmentioning

confidence: 99%

Effects of formoterol and ipratropium bromide on repeated cadmium inhalation-induced pulmonary inflammation and emphysema in rats

Fiévez

European Journal of Pharmacology

et al. 2010

“…Hepatic HYP was assessed as described by Patiyal and Katoch [23]. Hepatic MDA, GSH and CAT levels were measured colorimetrically according to Satoh,Beutler et al and Aebi [24,25,26], respectively, while MPO was assessed as described by Weiss et al [27].…”

Section: Assessment Of Liver Homogenate Biomarkersmentioning

confidence: 99%

Ameliorative Effect of Hesperidin on Carbon Tetrachloride Induced Liver Fibrosis in Rats

Abdel-sttar

Khalaf

Abo-Youssef

et al. 2017

Int J Pharm Pharm Sci

Objective: Exposure to carbon tetrachloride leads to serious liver injury and fibrosis. This study was aimed to evaluate the hepatoprotective effects of hesperidin against carbon tetrachloride (CCl4)-induced liver fibrosis in rats compared with the reference drug silymarin.Methods: Wistar albino rats were divided into five groups, each of eight rats. Animals were allocated into a control group, corn oil group and fibrosis control group. The remaining two groups received in addition to CCl4, silymarin (100 mg/kg/d) as a reference treatment and hesperidin (200 mg/kg/d). At the end of experimental period, the biomarkers of specific fibrosis [hepatic transforming growth factor β1 (TGF-β1) and hydroxyproline (HYP)], liver function [serum alanine transaminase (ALT), aspartate transaminase (AST), albumin and total bilirubin], oxidative stress [hepatic malondialdehyde (MDA), glutathione (GSH) and catalase (CAT)], inflammatory [hepatic myeloperoxidase (MPO), serum tumor necrosis factor alpha (TNF-α)], relative liver weight, lipid profile [total cholesterol, serum triglycerides, high-density lipoprotein cholesterol (HDLCh) and low density lipoprotein cholesterol (LDL-Ch)] were evaluated, supported by liver histopathological study and immunohistochemistry of alpha-smooth muscle actin (α-SMA) in liver sections.Results: Hesperidin significantly decreased hepatic transforming growth factor β1, hydroxyproline, the serum liver function markers of ALT, AST and total bilirubin, the hepatic content of MDA and MPO activity, the serum pro-inflammatory cytokine TNF-α, relative liver weight, and the serum lipid profile markers cholesterol, triglycerides and LDL. On the other hand, Hesperidin significantly increased albumin, the hepatic content of GSH and CAT, and serum lipid profile of LDL. In addition, liver sections obtained from these groups showed marked histopathological and immunohistochemistry of α-SMA improvement. Conclusion:Hesperidin may be promising protective agent against liver fibrosis through improvement of liver function, modulation of the fibrous scar formation, anti-inflammatory and antioxidant potentials.

“…Dietary administration of clenbuterol decreased androgen receptor (AnR) expression in testicle, glucocorticoid receptor (GR) expression in lymphoid tissues, and β-adrenergic receptor (β-AR) expression in targeted organs of chickens [3]. Clenbuterol caused an impairment of collagen turnover by down-regulating MMP-9 activity [11]. Clenbuterol not only enhanced muscle fiber size but also increased expression of GATA-2 protein in skeletal muscle of rat uterus [12].…”

Section: Introductionmentioning

confidence: 99%

Adverse Effects from Clenbuterol and Ractopamine on Nematode Caenorhabditis elegans and the Underlying Mechanism

Zhuang

Zhao

et al. 2014

PLoS ONE

In the present study, we used Caenorhabditis elegans assay system to investigate in vivo toxicity from clentuberol and ractopamine and the possible underlying mechanism. Both acute and prolonged exposures to clentuberol or ractopamine decreased brood size and locomotion behavior, and induced intestinal autofluorescence and reactive oxygen species (ROS) production. Although acute exposure to the examined concentrations of clentuberol or ractopamine did not induce lethality, prolonged exposure to 10 µg/L of clentuberol and ractopamine reduced lifespan. At relatively high concentrations, ractopamine exhibited more severe toxicity than clentuberol on nematodes. Overexpression of sod-2 gene encoding a Mn-SOD to prevent induction of oxidative stress effectively inhibited toxicity from clentuberol or ractopamine. Besides oxidative stress, we found that clentuberol might reduce lifespan through influencing insulin/IGF signaling pathway; however, ractopamine might reduce lifespan through affecting both insulin/IGF signaling pathway and TOR signaling pathway. Ractopamine more severely decreased expression levels of daf-16, sgk-1, skn-1, and aak-2 genes than clentuberol, and increased expression levels of daf-2 and age-1 genes at the examined concentration. Therefore, the C. elegans assay system may be useful for assessing the possible toxicity from weight loss agents, and clentuberol and ractopamine may induce toxicity through different molecular mechanisms.