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Dissection of the brain. A Bird brain structures. B Cerebral cortex sectioning (first and second steps). C Hindbrain sectioning (in two separate levels). D Cerebellar nuclei sectioning. E Midbrain sectioning
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Artemisinin has been used for centuries to treat malaria, intestinal tract helminthosis, diarrhea, and used as an antipyretic and sedative agent, but the usage in veterinary medicine is a new field. Recently, it has been used successfully to control experimental poultry coccidiosis. The present study aimed to determine the effects of different dose...
Citations
... According to Adamu et al. [25], the PCV value of the blood indicates that E. tenella infection in chickens has the potential to cause anaemia. Shahbazfar et al. [26] reported the effect of oral administration of various doses of artemisinin compounds on broiler chickens. Administration of 17-136 ppm did not induce clinical symptoms in chickens, except anaemia and a few brain lesions, depending on the amount of doses/concentration. ...
... Shahbazfar et al. [26] emphasised that the administration of artemisinin for the prevention and treatment of coccidiosis in chickens is relatively safe and does not cause severe organ damage when given at therapeutic doses, and has no effect on body weight gain, feed consumption, or water intake. According to Kheirabadi et al. [24], artemisinin is relatively slowly absorbed by the body, which is advantageous for the treatment of coccidiosis. ...
... The mode of action of artemisinin implies the production of free radicals and ROS due to the cleavage of its endoperoxide bridge and induction of oxidative stress, resulting in the inhibition of sarco/endoplasmic reticulum calcium ATPase of coccidia (162) and consequently in their death (163) . This phytochemical seems to have an adverse effect on weight gain and also on FCR when fed at higher concentrations (500 mg/kg) (161) , whereas concentrations lower than 150 mg/kg are considered safe (164) . ...
In the current post-antibiotic era, botanicals represent one of the most employed nutritional strategies to sustain antibiotic-free and no-antibiotic-ever production. Botanicals can be classified either as plant extracts, meaning the direct products derived by extraction from the raw plant materials (essential oils (EO) and oleoresins (OR)), or as nature-identical compounds (NIC), such as the chemically synthesised counterparts of the pure bioactive compounds of EO/OR. In the literature, differences between the use of EO/OR or NIC are often unclear, so it is difficult to attribute certain effects to specific bioactive compounds. The aim of the present review was to provide an overview of the effects exerted by botanicals on the health status and growth performance of poultry and pigs, focusing attention on those studies where only NIC were employed or those where the composition of the EO/OR was defined. In particular, phenolic compounds (apigenin, quercetin, curcumin and resveratrol), organosulfur compounds (allicin), terpenes (eugenol, thymol, carvacrol, capsaicin and artemisinin) and aldehydes (cinnamaldehyde and vanillin) were considered. These molecules have different properties such as antimicrobial (including antibacterial, antifungal, antiviral and antiprotozoal), anti-inflammatory, antioxidant, immunomodulatory, as well as the improvement of intestinal morphology and integrity of the intestinal mucosa. The use of NIC allows us to properly combine pure compounds, according to the target to achieve. Thus, they represent a promising non-antibiotic tool to allow better intestinal health and a general health status, thereby leading to improved growth performance.
... BOARETO & al. 2008 [3]). In broiler chickens, artemisinin causes decreases in the red blood cells count and hematocrit, anaemia, mild degeneration in renal tubules, hepatic degeneration with fatty changes, bile retention in liver, central chromatolysis in the brain and neuronal necrosis (H.A. ARAB & al. 2009 [2]; A.A. SHAHBAZFAR &. al. 2011 [20]). ...
... The toxicity of artemisinin and its derivates (artesunate, artemether, artenimol, arteether) in mammals is well documented and shown to induce neurotoxicity [20]). ...
... In previous studies, researchers have not found any lesions in the spleen after a single oral dose or even chronic oral intake kidney (H. [20]). The doses used by these researchers were 10, 50, 250, 1250 and 2500 mg/kg for the study of a single oral dose and 17, 34, 68, and 136 ppm for 36 days in the study of chronic oral intake. ...
The purpose of this study was to determine the side effects of artemisinin on the immune system of broiler chickens following chronic oral intake. Chickens were randomly divided into 4 groups: control group and three experimental groups that received 5, 50 and 500 ppm artemisinin in the feed. The effect of artemisinin on the chickens' immune system was assessed using the following criteria: morphometric changes in bursa of Fabricius, spleen, and thymus; changes in the concentrations of serum gamma globulins and functional activity of the immune response, lymphocyte proliferation assay and antibodies titres against sheep red blood cells. The lymphoid organs were negatively affected by the chronic consumption of artemisinin. Bursa was the most affected organ. The concentration of serum gamma globulins and antibody titres against sheep red blood cells were higher in the chickens exposed orally to artemisinin than in the control groups. The lymphocytes were stimulated by lipopolysaccharides, while artemisinin and concanavalin A caused a slight immunosuppression. The spontaneous phagocytic activity was significantly stimulated by the consumption of artemisinin and inhibited by the addition of concanavalin A. In vitro assays revealed a slight immunosuppression, mainly for T lymphocytes, even lymphoid organs were affected by high doses of artemisinin.
... In broiler chickens, there have been few reports of artemisinin toxicity in the liver, kidney, brain or hematological system (Arab el al. 2009, Shahbazfar et al. 2011, Pop et al. 2017, but the information is scarce. ...
... However, the authors used an alcoholic solution given directly by a crop tube, consequently most of the doses were higher than those employed in our study. Shahbazfar et al. (2011) observed the same pathological changes in the liver and kidney of broiler chickens as those found in the previous mentioned study, and they used similar dosages as used in the present study. These findings are in accordance with our results for the chickens treated with 50 and 500 ppm of artemisinin. ...
Artemisinin is a powerful antimalarial drug, useful in the treatment of many diseases, including chickens coccidiosis. Its toxic effects have been well studied in humans and experimental animals, but not sufficiently in broiler chickens. Therefore, in the present study, we aimed to assess the side effects of artemisinin in chickens, by measuring the serum level of proteins and enzymes (ALT, AST, GGT, ALP, CK), by histopathological examination and by the evaluation of relative weight of organs (liver, kidney, heart). Artemisinin was administered in the standard feed for chickens in three different concentrations: 5, 50 and 500 ppm. Each concentration of artemisinin increased the total serum proteins, gamma-globulins and the serum activity of CK and decreased the serum ALP level. The values of ALT and GGT were higher in the chickens treated with 50 and 500 ppm of artemisinin. Multifocal liver necrosis and inflammatory infiltrate were detected in the chickens that received the 50 and 500 ppm dosage of artemisinin. Minimal tubular necrosis, renal tubular epithelium vacuolation, multifocal interstitial nephritis and mild uric nephrosis were detected in chickens treated with the drug. Artemisinin administration produced no significant changes in the organs relative weight. Artemisinin, at a concentration of 5 mg/kg of feed is well tolerated by broiler chickens, but the concentrations of 50 and 500 mg/ kg feed can produce toxic effects.
... Prevention and treatment of coccidiosis in chickens with artemisinin is relatively safe and does not affect weight gain, feed and water consumption as long as given at the right dose (Shahbazfar et al. 2011) According to Kheirabadi et al. (2014), artemisinin is relatively slow to absorb the body which is advantageous for treatment of coccidiosis. The slow absorption allows prolong interaction of the active compound with parasites in the digestive tract. ...
p>The continuous use of anticoccidial drug in chicken often continuously generates drug resistance and tissue residue; so thatconsequently, a safe alternative anticoccidial drug based on herb is fundamentally required. The aim of thise study was to examine anticcocidial activity of artemisinin and extract of Artemesia annua leaves in chicken infected by Eimeria tenella. A total of 35 chickens of Cobb strain was divided into seven groups with five replicates birds per group, i.e. uninfected chicken group (P I), infected but untreated chicken group (P II), infected and treated chicken group with 8.5 ppm, 17 ppm, 34 ppm, for P III, P IV and P V respectively, infected and treated chicken with 17 ppm of A. annua extract (P VI) and infected and treated chicken with Sulfa (P VII). All chicken, except the uninfected group, whereas infected with 2000 infective oocyst of E. tenella except the uninfected group. Treatment was delivered by oral, once per day for eight days. The criteria observed were clinical manifestation of chickens, number of oocyst in feces, body weight, cecal lesion score, haematocrit (packed cell volume) and haemoglobin value. The results showed that extract of A. annua leaves (P VI) was the most effective treatment to reduce the number of oocyst in feces (74.18%), followed by 34 ppm of artemisinin group (P VII). In addition, application of A. annua extract and artemisinin was significantly able to decreased the cecal lesion score (P<0.05). Even though body weight and Hb value were not indifferent significantly different (p>0.05), however A. annua extract and artemisinin treatments were significantly able to hold PCV value on normal level compared to P II and P IV (P<0.05). It concluded that extract A. annua leaves and artemisinin could be used an alternative anticoccidial in chickens.</p
... Artemisinin inhibits the sporulation of Eimeria oocyst and has a damaging effect on sporulated oocysts (Fatemi et al. 2015;Dragan et al. 2010). On the other hand, despite the cautious use of artemisinin in dogs, the use of artemisinin in poultry has a high marginal safety and in very high doses, it may cause some adverse effects (Arab et al. 2009;Shahbazfar et al. 2011;Shahbazfar et al. 2012). Previous research shows A. annua has the highest concentration of artemisinin among the artemisia genus plants. ...
The effect of Artemisia annua ethanolic extract (AE) as a potential source of herbal anticoccidial activity was investigated on experimental coccidiosis in chicken. One hundred ninety-two one-day-old chicks were divided in to 8 groups (n = 24) including AE prevention group, AE-treated group, simultaneously challenged AE-medicated group, challenged-untreated group (positive control), unchallenged-untreated group (negative control), salinomycine prevention group, salinomycine-treated group, and simultaneously challenged salinomycine-medicated group, in a completely randomized design. Oral challenge carried out by a suspension containing a mixture of 200,000 oocysts Eimeria acervulina, 30,000 oocysts Eimeria necatrix, and 20,000 oocysts Eimeria tenella on day 21 of age. Weight gain in AE prevention group significantly increased compared to positive control group (p < 0.05). Unlike salinomycine prevention group, the food conversion ratio (FCR) of AE prevention group was not significantly higher than negative control. Oocyst per gram (OPG) in simultaneously challenged AE-medicated group had no significant difference, while for 38% of the days, in simultaneously challenged salinomycine-medicated group significantly decreased (p < 0.05). The food intake of AE-treated group had no significant difference with salinomycine-treated group (p > 0.05). In half of the days of OPGs sampling, AE-treated group was reduced significantly compared to positive control group (p < 0.05). Collectively, the in vivo study of anticoccidial effects of AE in the prevention section was more effective than the treatment section, while the treatment section was more effective than the simultaneous section. We concluded that AE has a potential value to use as an herbal medicine for preventive measure in chicken coccidiosis.
... Arab et al. (2009) showed that chickens treated with a single oral dose of artemisinin exhibited neurological signs, liver, kidney, and brain degeneration, especially at very high dosages, and presented a dose-dependent reduced feed intake. Shahbazfar et al. (2011) showed that after chronic intake of artemisinin, the chickens exhibited anaemia, dose-dependent decreases in haematocrit and red blood cells, and mild lesions in liver, kidney, and brain. The authors concluded that at therapeutic dosages, artemisinin causes no serious side effects. ...
... In a singleoral dose study, Arab et al. (2009) administered 10, 50, 250, 1250, and 2500 mg artemisinin/kg feed to 30-day-old chickens and noticed the same dose-dependent reduction in food intake. In contrast, Shahbazfar et al. (2011) did not report any negative effects on the weight gain or food intake, but they used lower doses of 17, 34, 68, and 136 ppm for 36 days. In this study, the tendency for a decreased number of erythrocytes, haemoglobin concentration, and PCV in the chickens supplemented with 500 ppm artemisinin suggests the evolution of anaemia. ...
... Based on the increased values of MCV, we can conclude that it is a macrocytic anaemia (Aslinia et al., 2006). Shahbazfar et al. (2011) noticed the clinical signs of anaemia in chickens fed 68 and 136 ppm artemisinin, including a significant reduction of the haematocrit in blood tests and of the RBC count, especially at higher concentrations of artemisinin. ...
In the present study, we aimed to assess the toxicity of artemisinin on the haematological system and its effect on the productive performance of broiler chickens. Eighteen-day-old chickens were randomly divided into four groups of 30 chickens (three replicates of 10 broilers/group): control group and three experimental groups: ART5 - diet with 5 ppm of artemisinin; ART50 - diet with 50 ppm of artemisinin; and ART500 - diet with 500 ppm of artemisinin. Artemisinin enhanced the productive performances of broiler chickens at the lowest concentration (5 ppm), but at the highest concentration (500 ppm), it negatively affected weight gain and the feed conversion ratio. The performance characteristics of the chickens whose diets were supplemented with 50 ppm artemisinin were similar to those of the control group. Additionally, 5 ppm artemisinin in feed did not significantly affect the haematological parameters of the chickens, but 50 and 500 ppm artemisinin induced a gradual decline of the total leukocytes, lymphopenia, monocytosis, and eosinopenia, and the highest concentration caused anaemia. Artemisinin at a low concentration could be used as a feed additive in the poultry industry to improve organic broiler production performance with no serious side effects.
... Thus, it seems that in addition to the first pass effects and hepatic metabolism induction, poor and incomplete absorption can also be effective in decreasing bioavailability and subsequently low serum level of Artemisinin. Human and animal toxicological studies indicated very high therapeutic index and low toxicity of Artemisinin even at high therapeutic and toxic doses (China Cooperation Research Group 1982, Arab et al., 2009, Shahbazfar et al., 2011. It seems that low absorption and bioavailability may be an important reason for the high therapeutic index of Artemisinin. ...
Keywords Abbreviations Abstract Although preliminary studies have shown the anticoccidial effects of Artemisinin in broiler chickens, there are no proofs of its pharmacokinetics. The objective of this study was to determine the serum concentration of Artemisinin after single and multiple oral administration in broiler chickens. A total of 390 one-day-old healthy Ross 308 chickens were divided randomly into two groups. In the first group, single oral doses of 0, 1, 5, 25, 125, 250, 500 and 1000 mg/kg Artemisinin were given on day 44, and in the second group 0, 17, 34, 68 and 136 ppm of Artemisinin were given chronically in the diet over a 36-day period. An HPLC system with UV detector was used to determine serum level of Artemisinin. Data were presented as Mean ± SE and analyzed using the linear mixed model (p < 0.05). The results showed that in both groups the serum levels of Artemisinin were generally very low and there were no significant differences between multiple and single dose administration groups or between different doses in each group (p < 0.05). The serum levels of Artemisinin in the chickens that had received single doses were in the range of 25.38 ± 0.15 to 42.27 ± 12.04 ng/ml and 24.68 ± 0.12 to 29.24 ± 1.72 ng/ml for those that had received chronic doses. It can be concluded that serum level of Artemisinin administered orally to the chickens as single or chronic doses is low which seems to be due to low oral absorption and metabolism induction and thus, can have high therapeutic index and good anticoccidial properties. HPLC: High Performance Liquid Chromatography A. annua: Artemisia annua OPG: Oocyst Per Gram (of feces) A. sieberi: Artemisia sieberi SEM: Standard Error of the Mean AUC: Area Under the Curve SD: Standard Deviation RSD: Relative Standard Deviation Artemisinin, serum level, broiler chickens, HPLC
... Further study showed that multiple administration of high doses of artemisinin in broiler chickens was not effective on different organs including the heart, the lung, and the spleen; but it induced various changes in the liver, the kidney, and the brain. It was found that, while there was not any relationship between the severity of the liver alteration and the drug administration, the severity of lesions in the brain was dose dependent (Shahbazfar et al., 2011). ...
... In the spleen, the lowest level was found following single oral doses, in agreement with this, previous histopathologic studies showed no lesions in the microscopic sections of the spleen following administration of single or multiple doses of artemisinin (Arab et al., 2009;Shahbazfar et al., 2011). However, in the present study, considerable accumulation of artemisinin was observed following administration of multiple doses of artemisinin. ...
BACKGROUND: Artemisinin is commonly used for the treatment of malaria, but recently has been considered as a potential substance to control poultry coccidiosis. OBJECTIVES: The aim of the present study was to determine the tissue distribution of artemisinin following single or multiple oral administration of different doses in broiler chickens. METHODS: A total number of 390 one day old Ross broiler chicks were divided randomly into two main groups, in the first group 0, 1, 5, 25, 125, 250, 500 or 1000 mg/kg artemisinin as a single oral dose was administered on day 44, but the second group were treated with 0, 17, 34, 68 or 136 ppm artemis-inin from day 8 to day 44. The HPLC system was used to determine the level of artemisinin in different tissue samples. Data were assessed using one way analysis of variance (ANOVA) followed by the Tukey's test (p<0.05). RESULTS: Maximum concentrations of artemisinin were found in the liver of chickens in both groups in a dose dependent manner. While, the minimum level was determined in the brain and the kidney of chickens received multiple artemisinin administration ; in the spleen of those chickens a single oral dose was administered. The concentration of artemisinin in the brain reached a plateau at 68 ppm in multiple administration and 125mg/kg at single dose, no shift was found with dose increment. CONCLUSIONS: It can be concluded that tissue accumulation of artemisinin is time and dose dependent. Moreover , redistribution, saturation effect and tissue selectivity were also observed.
... Inhibitory activity against coccidia of birds was also reported (Allen et al., 1997). However, in chickens toxic side effects were described following application of the compound (Arab et al., 2009;Shahbazfar et al., 2011). In a previous study investigating the effect of artemisinin against histomonosis, artemisinin (100 and 2600 mg/kg feed) was administered to day-old turkey chickens (Thofner et al., 2012). ...
