الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Addiction is a chronic disease characterized by compulsive drug seeking and uses. Drugs abuse cause and contribute to the deaths of millions of people each year by worsening comorbid psychiatric symptoms, such as depression, and medical conditions, such as cirrhosis of the liver, while also aiding in the spread of infectious diseases such as human immunodeficiency virus (HIV), hepatitis B and hepatitis C. Drugs abuse are also linked to crime and disability .
Although research on drug abuse is too much in the Western world, there are few reports regarding drug abuse effects on antioxidant status. In spite of its fatal consequences worldwide, research on illicit drug use has received relative little attention in Egypt.
The abuse liability of naturally occurring opiates (e.g., morphine, codeine) and synthetic opioids (e.g., heroin, oxycodone, buprenorphine) is well known. An estimated 9.2 million people worldwide are regular users of heroin. The abuse of other opioids, including analgesics like oxycodone, is also widespread. Opioids can significantly depress respiration, making overdose the most common cause of death among heroin users.
Heroin addiction is infiltrating all areas of the globe, and heroin addiction is an insidious, progressive, fatal disorder, which ends in death. chronic heroin addiction may lead to very serious medical problems. Heroin first attacks the abuser’s brain by altering large amounts of neurontransmitters, then it begins to affect the person’s vital organs.
Most of phenomena occurring in heroin addicts, such as aging, abscesses, arthritis, other rheumatologic disorders and immunity disorders are related to degenerative diseases.There are some indirect evidences showing the relationship between heroin addiction and the products of free radical reaction. Heroin is able to induce oxidative cell injury in neuronal cells, as well as, neurodegeneration.
Tramadol hydrochloride is a centrally acting synthetic opioidanalgesic used to treat moderate to moderately severe pain. Tramadol is a weak μ-opioid receptoragonist, a serotonin releaser and a reuptake inhibitor of norepinephrine.
Tramadol’s physical dependence capacity is important to quantify, as it provides one index of tramadol’s opioid agonist effects, is informative regarding tramadol’s abuse potential when used as an analgesic, and also can provide data relevant to its potential development as a treatment for opioid dependence.
Several evidences support a role for oxidative stress(OS) in the toxicity induced by many drugs of abuse in different organs, such as the brain, heart, liver and kidneys. However, the effects of drugs of abuse on the central nervous system (CNS) are crucial for the development of drug addiction, which can be considered a brain disease.
Advanced oxidation protein products (AOPPs) areused as an OS marker. AOPPsare formed during OS by the action of chlorinated oxidants, mainly hypochlorous acid and chloramines (produced by myeloperoxidase in activated neutrophils).AlsoAOPPs are widely used into the field of OS, as a marker of plasma protein oxidative damage.
Advanced glycation end products(AGEs), are substances that can be a factor in the development or worsening of many degenerative diseases, such as diabetes, atherosclerosis and chronic renal failure.AGEs affect nearly every type of cell and molecule in the body and are thought to be one factor in aging and some age-related chronic diseases. They are also believed to play a causative role in the vascular complications of diabetes mellitus.
Advanced glycation end products are a heterogeneous, complex group of compounds. The deleterious effects of AGEs in different tissues are attributed to their chemical, pro-oxidant, and inflammatory actions.
Several methods have been developed to measure the total antioxidant capcity(TAC) and the most common of these methods are the oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP).The FRAP assay is a simple, rapid, and relatively inexpensive assay to determine the TAC of blood.
Lactoferrin is considered a key component in the host’s first line of defense, as it has the ability to respond to a variety of physiological and environmental changes. It is involved in several physiological functions, including: regulation of iron absorption in the bowel; immune response; antioxidant, anticarcinogenic and anti-inflammatory properties; and protection against microbial infection.
Consequently this work aimed to studying the effects of illicit drugs (Tramadal and Heroin) on some biochemical and hematological parameters, in order to elucidate their deleterious effects on the body systems. AOPPs, AGEs were measured as markers of OS. FRAP was also be measured to represent inherent antioxidant power andplasma lactoferrin level was measured as a marker of neutrophils activation.
In the present study there were significant increased levels of kidney (urea & creatinine) function tests indicates impairedkidney functions due to repeated exposure to tramadol and heroin and its metabolites. Alsothe present study showed significant increase in the levels of liver enzymesalanine transaminase and aspartate transaminase(ALTand AST) in all addicted groups compared to control the group (p ≤ 0.05).This laboratory evaluation in ALT and AST activities could be a common sign of impaired liver functioninduced by consuming of heroin and tramadol in addicts .
In the presentstudy there was significant increase in oxidative stress parameters AOPPs and AGEs in all addicts groups compared to control group(p ≤ 0.05), while FRAP level in alladdicts groupswassignificant decrease compared to control group(p ≤ 0.05).
from the above observation, it can be concluded that heroin, morphine and opiate are able to induce ROS formation in various cells and decrease the antioxidant defense system..
Lactoferrinshowed significantly increased in all cases groups compared to control group (p ≤ 0.05).So the significant increase in lactoferrin levels could be a normal response to administration of tramadol and heroin.
Increasedlactoferrin level can be considered as a compensatory mechanism to counteract the increased levels of ROS induced by tramadol and heroin.
C - reactive protein showed significantly increase in all addicts groups compared to control group (p ≤ 0.05).thus opioids may induce a change in the metabolic pathways responsible for the production of CRP.
Higher levels and proportions in all the studied groups are indicative of increased liver synthesis following consumption of the illicit drugs, infection and cytokine release. In addition, the increases indicate heightened liver damage through illicit drug.