الفهرس 
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Abstract
Food-food, food-herb and herb-herb interactions are considered serious problems, which greatly affected human health. However, many studies were interested of drug-drug, drug-herb and drug-food interactions. Several patients treated with monoamine oxidase inhibitors as antidepressant drugs were suffered from hypertensive crisis, acute heart failure, brain hemorrhage, and may be sudden death after they had eaten food containing biogenic amines. With observation that natural MAO reversible inhibitors were found in a number of foods and herbs such as curcumin in turmeric, piperine in black pepper, berberine, quercetin, resveratrol, anthocyanins, coumarin derivatives and ginkgo biloba.
Therefore, the present study was performed to determine the adverse effects of interaction between food containing biogenic amines and food or herb containing monoamine oxidase inhibitors. To achieve this aim, Thirty five male Albino rats weighing about 100g were purchased, divided into 5 groups and treated with the following treatments by an oral administration every other day for 60 days:
group (1): Fed on a normal diet and served as a control.
group (2): Fed on Tyramine (20 mg/kg) + Curcumin (40 mg/kg).
group (3): Fed on Tyramine (20 mg/kg) + Piperine (30 mg/kg).
group (4): Fed on Dopamine (20 mg/kg) + Curcumin (40 mg/kg).
group (5): Fed on Dopamine (20 mg/kg) + Piperine (30 mg/kg).
The adverse effects occurring for experimental rats with oral administration of both biogenic amines (e.g. tyramine or dopamine) + MAO inhibitors (e.g. curcumin or piperine) were investigated through determination of blood pressure measurements, hematological analyses and different blood biochemical assays (e.g. AST, ALT, CPK, LDH enzymes, glucose, albumin, triglycerides, cholesterol, creatinine, uric acid & urea).
This study was also carried out to study the following points:
• Determining the activity of monoamine oxidase (MAO) extracted from different organs (e.g. brain & liver) on different substrates (e.g. tyramine & dopamine).
• Studying the kinetics of MAO through determination of its activity with different concentrations of tyramine or dopamine, and calculation of enzyme constants (e.g. Vmax & Km).
• Examining the inhibitory effect of different natural compounds (e.g. curcumin & piperine) on the activity of MAO through determination of inhibition type and IC50.
The results of this study can be summarized as follows:
A. Blood pressure:
Significant (p≤0.05) increases of systolic and diastolic blood pressure were observed for all treatments compared to the control group. The highest increase of blood pressure (193/151 mmHg) was recorded for the rats treated with tyramine + piperine while the lowest increase (164/127 mmHg) was recorded for the rats treated with dopamine + curcumin.
B. Hematological analyses:
No significant (p≤0.05) differences were noticed among the levels of hemoglobin (HGB), hematocrit (HCT), red blood cells (RBC), white blood cells (WBC) and platelets (PLT) counts for all treatments compared to the control group.
C. Blood biochemical assays:
1. Kidney functions:
The data showed no significant (p ≤ 0.05) differences among the levels of serum urea and uric acid, and slight increases in the levels of serum creatinine for all treatments which received the different mixtures of biogenic amines + MAOIs during the experiment period (60 days).
2. Liver functions:
There were no significant (p≤0.05) differences among the levels of serum albumin and the activities of ALT for all treatments compared to the control group. Conversely, there were significant (p≤0.05) increases in the activity of AST for all treatments compared to the control.
3. Heart functions:
All treatments recorded significant (p≤0.05) increases in the activities of CPK and LDH enzymes compared to the control.
4. Blood glucose:
All treatments recorded high levels of blood glucose especially the treatment with dopamine + piperine (187.7 mg/dl).
5. Lipid profile:
Significant (p≤0.05) increases of serum total cholesterol and triglycerides were noticed for all treatments compared to the control. It can be observed that increases of serum triglycerides were pronounced more than those of total cholesterol for all treatments.
6. Electrolytes:
The data showed no significant (p ≤ 0.05) differences among the levels of serum sodium, and slight increases in the levels of serum potassium for all treatments compared to the control.
D. Monoamine oxidase (MAO) assays:
1. MAO activity:
The specific activity of brain MAO enzyme was greatly higher than that of liver MAO enzyme by using tyramine as a substrate. On the contrary, the specific activity of liver MAO enzyme was relatively higher than that of brain MAO enzyme by using dopamine as a substrate.
2. MAO kinetics:
Studying the effect of concentration of tyramine or dopamine as substrates on the specific activity of brain and liver MAO enzymes showed gradual increases of the specific activity of these enzymes by increasing of the substrate concentration. The highest specific activities of brain and liver MAO enzymes were recorded at concentration of 300 µM of tyramine or dopamine. Also, the values of Km and Vmax for brain and liver MAO enzymes are calculated from the Lineweaver-Burk plots.
3. MAO inhibition:
As indicated by the Km and Vmax values which changed in the presence or absence of the inhibitor, the inhibitory action of piperine on brain MAO enzyme was of mixed type. Piperine inhibited the activity of liver MAO enzyme with IC50 value of 3.1µM while rasagiline inhibited the activity of liver MAO enzyme with IC50 value of 0.7µM.