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  • Pathological changes in animal are powerful indicators of th


    Pathological changes in animal are powerful indicators of the exposure to environmental stressors. The liver serves as an appropriate organ for the study of pollutant effects because of its high capacity to accumulate pollutant and its susceptibility to histopathological damage by pollutants (Padmini et al., 2009). Our histological results showed that NB-treated drakes were negatively affected at the tissue level. The histopathological changes we observed in the liver tissues were similar to the typical histological responses to the pollutants (Sigala et al., 2004, Ortega et al., 2005). Presently, there are no available data in the open literature regarding histological effects of NB on birds. In our study, NB caused alterations to the liver structure of the drakes, as evidenced by lymphocytes infiltration in the header, hydropic degeneration, pyknotic nuclei and focal necrosis of liver Imeglimin hydrochloride receptor as well as, structural disorder of the liver cell cable, which may subsequently influence normal physiological activities. The aberrant hepatic cells may disturb the normal metabolism of the organisms, thereby inducing diseases and even death.
    Introduction The Cytochrome P450 (CYP450) enzymatic system constitutes the most important pathway for drug metabolism and elimination in humans. Nowadays, 57 different isoenzymes have been characterized in the human body and classified in different families and subfamilies [1], [2]. The most important families involved in drug metabolism are the CYP1, CYP2 and CYP3. The CYP3A and particularly the CYP3A4/5 are major isoenzymes implicated in the metabolism of about 50% of drugs (e.g. calcium channel blockers, statins, anesthetic, immunosuppressive, benzodiazepine) [3], [4]. The CYP2D, CYP2C, and CYP1A subfamilies are also implicated in the metabolism of many drugs, and particularly their major isoenzymes namely, CYP2D6 (e.g. dextromethorphan, β-blockers, antiarrhythmic agents) [3], [5], CYP2C9 (e.g. nonsteroidal anti-inflammatory drugs, S-warfarin, losartan) [3], [6] and CYP2C19 (e.g. tricyclic antidepressants, proton-pump inhibitors, R-warfarin, clopidrogrel) [3], [5], and CYP1A2 (e.g. caffeine, theophylline, mexiletine) [7]. To a lesser extent, the CYP2E1 isoenzyme takes part in the metabolism of some drugs such as chlorzoxazone, acetaminophen or inhalation anesthetics [3], [8]. Finally, the interest in CYP2B6 metabolism has increased recently as its role in the metabolism of substrates (e.g. bupropion, cyclophosphamide, ifosfamide, methadone) has been demonstrated [9], [10]. Wide inter-individual differences in expression or activity of CYP450 contribute to variations in both clearance and efficacy/toxicity of several drugs. Phenotyping measures provide information on the real-time activities of CYP450 and provide clinically relevant information as they reflect the combination of factors such as genetic, drug–drug interactions, environmental and endogenous factors including diseases [11], [12], [13], [14], [15], [16]. Thus, a phenotyping measure using selective CYP450 probes is a valuable tool to determine in vivo CYP450 activities. In vivo methods to characterize subject’s phenotype may involve either the administration of single probe drugs, one at a time, on numerous occasions or a mixed phenotyping approach based on a cocktail method where multiple CYP450-probe drugs are administered simultaneously. The major advantage of the cocktail approach is to provide information on several CYP450 activities in a single experiment. However, drugs used in these cocktails must be specific for individual CYP450 isoenzymes and should not interact with each other. Also, in order to use such cocktails in a clinical setting, i.e. in patients with several co-morbidities, probe drugs should be given at low oral doses to minimize drug exposure and ensure patient’s safety. Numerous cocktails composed of several CYP450-selective probe drugs have already been described in the literature to study in vivo drug-metabolism activities [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31]. Although previous published cocktails such as Inje, Karolinska, Cooperstown 5+1 or Pittsburg cocktail have shown value they also suffer from many limitations [24], [26], [27], [28], [29], [31]. For instance, they often comprise probe drugs which are not or no longer available in several countries. Furthermore, they have been validated using high performance liquid chromatography methods with limited detection sensitivity. This led to the utilization of high doses of probe substrates.