| Version | Summary | Created by | Modification | Content Size | Created at | Operation |
|---|---|---|---|---|---|---|
| 1 | Chung-Der Hsiao | -- | 3045 | 2022-09-27 12:09:08 | | | |
| 2 | Lindsay Dong | -39 word(s) | 3006 | 2022-09-28 02:52:05 | | |
Ractopamine (RAC) is a synthetic phenethanolamine, β–adrenergic agonist used as a feed additive to develop leanness and increase feed conversion efficiency in different farm animals. While RAC has been authorized as a feed additive for pigs and cattle in a limited number of countries, a great majority of jurisdictions, including the European Union (EU), China, Russia, and Taiwan, have banned its use on safety grounds. RAC has been under long scientific and political discussion as a controversial antibiotic as a feed additive.
RAC is the first βAR ligand to be cleared for use in pigs in the United States. RAC is structurally similar to the natural catecholamines epinephrine and norepinephrine and binds with high affinity to βAR in pig adipose and muscle tissue. Primary attention has been given to understanding how βAR might mediate increased growth and protein accretion [39]. Catecholamines (CAs) are a group of organic compounds consisting of a hydroxyl group and an amine side chain. Most CAs are used by dopamine, norepinephrine, and epinephrine receptors in the nervous system [40][41]. CAs have received the attention of researchers because of their early recognized involvement in different neurological disorders [42]. The biological effect of CAs is mediated by two receptors, namely α- and β-adrenergic receptors, and sometimes they are collectively called adrenoreceptors. Alpha- and beta-adrenergic receptors have different locations in animal tissues and respond differently and often oppositely to catecholamines [43]. An adrenoreceptor stimulated by an α-agonist leads to intracellular effects mediated by adenylate cyclase inhibition. This stimulates smooth muscle contraction in blood vessels that supply peripheral organs such as skin and kidneys, smooth muscle relaxation in the gastrointestinal tract, and blood platelet aggregation. However, stimulating β-adrenergic receptors by β-agonists activates adenylate cyclase, leading to increased glycogenolysis and gluconeogenesis in the liver and skeletal muscle and increased lipolysis in adipose tissue [44]. Increased blood flow to the brain activates the catecholamine, making animals cope with stressful conditions such as reducing feed during the dry period, mixing animals in unfamiliar groups, transportation, and rough handling [45]. However, the measurement of CAs in urine and the brain cannot provide a clear picture of stress, fear, and temperament. Some scientists consider CAs a coping hormone as they provide energy to the brain and help reduce deficiency, leading to “energy deficiency syndrome” of the brain [46].
The fast development in aquaculture systems is managed by different factors, including the growing consumption of formulated aqua-feeds and a massive improvement in the culture systems [57][58]. Phenethanolamines (PEOHs) act as a nutrient dissemination agent in intermediary metabolism by transferring nutrients from adipocytes to muscle protein unification [47][59][60]. The rationing of PEOH in fishes is not a common practice as fishes have lower energy demand and thus respond to diets with a higher protein–energy ratio than birds and mammals [61]. Previous data showed that RAC supplementation in channel catfish (Ictalurus punctatus) promoted weight gain and reduced fat deposition [62]. RAC feeding at 20 mg/kg or lower resulted in a 17% increase in weight gain and a 24% reduction in muscle fat in catfish [63]. In combination with dietary protein supplements in catfish, RAC yielded higher weight gain than when RAC was only combined with restricted protein supplementation [64]. In varying concentrations, RAC has been found to increase the feed efficiency in rainbow trout (Oncorhynchus mykiss) (walbaum) while maintaining normal hepatosomatic and viscerosomatic indices throughout the feeding weeks [65]. In another study, the combined effect of RAC at 0 and 10 mg/kg and l-carnitine at three levels (0, 1, and 2 g/kg) showed that 1 g/kg l-carnitine and 10 mg/kg RAC improved growth performance, feed efficiency, and protein efficiency ratio in juvenile rainbow trout. The combined use of l-carnitine and RAC in trout diets increased body protein, reduced body fat, and altered the fatty acid profile of muscle tissue [66]. Increasing levels of RAC in the diet of juvenile pacu (Piaractus mesopotamicus) for 60 days did not improve body growth or composition but only altered the hematological and biochemical parameters [67]. Pacu (Piaractus mesopotamicus) fed with 33.75 ppm of RAC in the finishing phase developed less fat content in its meat and improved antioxidant status inside the freezer [68].
The utility of the zebrafish model for evaluating RAC toxicity is very well recognized because the manifestations of toxicity are widely demonstrated in this model [75]. For instance, RAC exposure of zebrafish at different concentrations for seven days exhibited altered behavior and imbalanced oxidative status [76]. Zebrafish larvae acutely exposed to RAC displayed altered heart rate and locomotory and exploratory behavior but maintained their survival rate [77]. In addition, adult male zebrafish exposed to RAC for 21 days revealed poor reproduction and breeding capability and altered behavior [78]. In the same study, the mating of RAC-fed male adult zebrafish with non-RAC-fed female adult zebrafish resulted in delayed hatching (72 hpf) and a significant number of abnormal embryos with stunted development, edema of the heart, granule formation, degenerated yolk, and yolk deformities.
Amendola et al. utilized a GC-ion trap to select precursor and product ions in monitoring the clenbuterol spike in human urine [79]. Nanoparticles were also utilized to extract and detect RAC and salbutamol by an electrochemical process. Rajkumar et al. used glassy carbon electrode-modified poly taurine/zirconia nanoparticles (ZrO2) to identify RAC and salbutamol in swine muscle and human urinary samples [80]. With an additional derivatization procedure, HPLC-UV was a popular method to detect RAC in porcine muscle and urine samples [81][82][83]. Nowadays, RAC levels can be estimated by high-performance liquid chromatography (HPLC) coupled with MS detection or HPLC coupled with tandem MS (MS/MS) [84]. Ultra-pressure liquid-phase chromatography (UPLC) coupled with triple-quadrupole MS was utilized to detect RAC within 5 min [81][85].