الفهرس 
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Abstract
Analgesics are the most commonly consumed over the counter preparations all over the world. Tramadol hydrochloride, a synthetic analogue of codeine, is a centrally acting analgesic drug. After its introduction in the 70s, tramadol gained great interest because it is prescribed for moderate to severe pain (Decker, et al., 2008).
Tramadol is an available worldwide synthetic centrally acting analgesic for treatment of moderate to severe acute or chronic pain (Nossaman, et al., 2010), with effects similar to those of codeine and 10 times less than morphine (Marquardt, et al., 2005).
Most reports suggested that the analgesic activity and other clinical effects of tramadol are a result of opioid and non-opioid mechanisms. Tramadol binds to the μ -opioid receptors in the brain, though much more weakly than morphine. It is only 1/6000 of that of morphine although its selectivity for this sub-type of receptor is greater than that of morphine (Volpe, et al., 2011).
Tramadol, and its metabolite, known as M1, have been found to bind to μ-opioid receptors thus exerting their effect on GABAergic transmission, and to inhibit reuptake of 5-hydroxytryptamine (5-HT) and noradrenaline. The second mechanism is believed to be important since the analgesic effects of tramadol are not fully antagonized by the μ - opioid receptor antagonist naloxone (Gasse, et al., 2000).
Nowadays tramadol-induced hepatotoxicity is a clinically and economically important problem. The liver and kidneys are responsible for the metabolism and excretion of opioids, which may cause hepatotoxicity and nephrotoxicity during its metabolism (Janssen, 2005).
Tramadol has the potential to trigger two dramatic events namely seizures (due to lowering of the seizure threshold) and serotonin syndrome (due to increase of cerebral serotonin activity) (Vizcaychipi, et al., 2007).
Acute poisoning with antipsychotic drugs is an important cause of referring intoxicated patients to the hospital (Ciranni, et al., 2009)
Haloperidol (HA), a classic butyrophenone antipsychotic, has been used as model of antipsychotic intoxication in several studies. Moreover, it has been suggested that some of HA properties, such as high lipid solubility and water-soluble metabolites with low pharmacological activity, make ILE suitable for the treatment of HA intoxication (Moshiri, and Etemad, 2011).
Haloperidol intoxication can induce catalepsy and other neurological manifestations that can be evaluated in animal models. As it is a potent typical antipsychotic, HA intoxication has shown higher incidence of catalepsy and extrapyramidal manifestations. Hypothermia and anticholinergic manifestations are other common signs of HA intoxication. The mainstay of treatment in acute HA overdose is supportive and there is no specific antidote (Biała, 2000).
Intravenous lipid emulsion (ILE) is used as a source of calories and essential fatty acids in patients who require parenteral nutrition (Arslan, et al., 2013).
Lipid emulsion has been promoted in the resuscitation of local anesthetic toxicity refractory to conventional modes of resuscitation (Picard, et al., 2009).
In addition, its successful use in case reports and animal studies of drug toxicity other than local anesthetics has been reported (Arslan, et al., 2013).
(Kosh, et al., 2010) recommended that ILE 20% should be available whenever patients receive large doses of local anesthetics in operating rooms and emergency departments.
The aim of this study is to assess the effects of intravenous lipid emulsion in treatment of Tramadol and Haloperidol toxicity on different biochemical and pathological parameters of liver, kidney and brain in adult male albino rats.
The study was carried out on 180 adult male albino rats weighting 150-200 g .The duration of the study was two days.
Rats were divided into six groups as the following:
group I (Control group): Each rat of this group received only regular diet and tap water for 48 hours.
group II (Intravenous lipid emulsion group): Animals of this group treated with different doses of intravenous lipid emulsion (Carreiro, et al., 2013) which is further subdivided into subgroups IIA, IIB and IIIC
Sub group IIA: (n=10 rats) each animal of this group received 10 ml / kg of intravenous lipid emulsion by I.V. once.
Sub group IIB: (n=10 rats) each animal of this group received 15 ml / kg of intravenous lipid emulsion by I.V. once.
Sub group IIC: (n=10 rats) each animal of this group received 19 ml / kg of intravenous lipid emulsion by I.V. once.
group III (Tramadol group): which is further subdivided into subgroups IIIA, IIIB.
Sub group IIIA: (n=15 rats) each animal of this group received (200mg/kg body weight) of tramadol orally by gavage once.
Sub group IIIB: (n=15 rats) each animal of this group received (250mg/kg body weight) of tramadol orally by gavage once.
group IV (Tramadol + ILE group): This is further subdivide into subgroups IVA, IVB.
Sub group IVA: (n=15 rats) this is further subdivide into subgroups IVA1, IVA2 and IVA3.
Sub group IVA1: (n=five rats) each animal of this group received (200mg/kg body weight) of tramadol orally by gavage once. Thirty minutes later, received 10 ml / kg of intravenous lipid emulsion (ILE) by I.V. once.
Sub group IVA2: (n=five rats) each animal of this group received (200mg/kg body weight) of tramadol orally by gavage once. Thirty minutes later, received 15 ml / kg of intravenous lipid emulsion (ILE) by I.V. once.
Sub group IVA3: (n=five rats) each animal of this group received (200mg/kg body weight) of tramadol orally by gavage once. Thirty minutes later, received 19ml / kg of intravenous lipid emulsion (ILE) by I.V. once.
Sub group IVB: (n=15 rats) this is further subdivide into subgroups IVB1, IVB2 and IVB3.
Sub group IVB1: (n=five rats) each animal of this group received (250mg/kg body weight) of tramadol orally by gavage once. Thirty minutes later, received 10 ml / kg of intravenous lipid emulsion (ILE) by I.V. once.
Sub group IVB2: (n=five rats) each animal of this group received (250mg/kg body weight) of tramadol orally by gavage once. Thirty minutes later, received 15 ml / kg of intravenous lipid emulsion (ILE) by I.V. once.
Sub group IVB3: (n=five rats) each animal of this group received (250mg/kg body weight) of tramadol orally by gavage once. Thirty minutes later, received 19 ml / kg of intravenous lipid emulsion (ILE) by I.V. once.
group V (Haloperidol): each animal of this group received a single dose of Haloperidol intraperitoneal (2.6 mg/Kg) .
group VI (Haloperidol + ILE group): This is further subdivide into subgroups VIA, VIB and VIC
Sub group VI A: (n=10 rats) each animal of this group received a single dose of Haloperidol intraperitoneal (2.6 mg/Kg) following by 10 ml / kg of intravenous lipid emulsion by I.V. once.
Sub group VI B: (n=10 rats) each animal of this group received a single dose of Haloperidol intraperitoneal (2.6 mg/Kg) following by 15 ml / kg of intravenous lipid emulsion by I.V. once.
Sub group VI C: (n=10 rats) each animal of this group received a single dose of Haloperidol intraperitoneal (2.6 mg/Kg) following by 19 ml / kg of intravenous lipid emulsion by I.V. once.
from the previous results, it can be concluded that:
• Tramadol caused elevation in serum ALT, AST, serum Creatinine and Urea after single administration of 200 mg/kg or 250 mg/kg.
• Tramadol caused hypoglycemia after single administration of 200 mg/kg or 250 mg/kg.
• Dramatically raised of Serum creatinine phosphokinase Level after tramadol intoxication.
• Tramadol altered the pathology of liver, kidney and brain after single administration of 200 mg/kg or 250 mg/kg.
• The treatment of tramadol intoxication with dose of 10 mL/kg of intravenous lipid emulsion (ILE) could significantly decrease in serum ALT, AST, serum Creatinine and Urea. In addition, elevation in serum Glucose level.
• The treatment of tramadol intoxication with intravenous lipid emulsion (ILE) could significantly improvement of pathology of liver, kidney and brain.
• Intravenous lipid emulsion could powerfully reduce creatinine phosphokinase levels to normal ranges when administered in both doses (10 and 15 mL/kg), but the decrease was more significant with dose of 15 mL/kg.
• Administration of intravenous lipid emulsion with dose of 19 mg /kg in treatment of tramadol intoxication caused more elevation in creatinine phosphokinase levels.
• Mortality occur with dose intravenous lipid emulsion in dose of 19 mg /kg.
• Haloperidol caused elevation in serum ALT and AST after administration of dose of 2.6 mg/kg.
• Haloperidol not effect on serum urea and creatine.
• Haloperidol altered the pathology of liver, kidney and brain.
• Haloperidol not effect on Serum creatinine phosphokinase Level.
• The treatment of haloperidol intoxication with dose of 10 mL/kg of intravenous lipid emulsion (ILE) could significantly decrease in serum ALT and AST.
• Administration of intravenous lipid emulsion with dose of 19 mg /kg in treatment of haloperidol intoxication caused more elevation in serum ALT and AST.
• The treatment of haloperidol intoxication with intravenous lipid emulsion (ILE) could significantly improvement of pathology of liver, kidney and brain.