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Abstract In The Present Investigation, The Possible Curative And Protective Effects Of Ursodeoxycholic Acid (UDCA), Resveratrol (RSV) And N-Acetylcysteine (NAC) On NAFLD In Rats Were Studied. Two Models Were Used In This Study; A Curative Model And A Protective Model. The Duration Of The Curative Model Was 2 Months And That Of The Protective Model Was 1 Month. In Both Models, Rats Received Treatments For Only One Month. UDCA, RSV Or NAC And Their Combinations Were Dissolved In Freshly Prepared Solution Of 0.75% Tween 80%, Water And Saline, Respectively. They Were Given Daily By The Oral Route Through An Orogastric Catheter With Doses Of 25 Mg/Kg/Day, 10 Mg/Kg/Day And 20 Mg/Kg/Day, Respectively. The Degree Of Fatty Liver Steatosis And Hepatic Injury Was Assessed By Measuring Liver Index, Liver Function Tests Such As Serum ALT And AST Activities As Well As Serum TNF-Α Level. Oxidative Stress Biomarkers Like Hepatic MDA, GSH Contents And GST Activity Were Also Measured. Liver Histophathology Was Also Inspected. Liver Integrity And Secondary Nephropathy Were Investigated By Measuring Serum Glucose And Albumin In Addition To Serum Urea And Creatinine. Lipid Profile Was The Most Important Variable Tested In This Study. It Included Total Cholesterol, Triglycerides, High Density Lipoproteins-Cholesterol, Low Density Lipoproteins-Cholesterol And Very Low Density Lipoproteins-Cholesterol In Addition To The Leptin Hormone Level In Serum. The Main Findings Of The Present Study Can Be Summarized As Follows I. Curative Model Of Steatosis 1-Effect Of Daily Oral Administration Of Ursodeoxycholic Acid On The a- Degree Of Fatty Liver Steatosis And Hepatic Injury Lowered Significantly TNF-Α Mean Value And The Liver Function ALT Mean Value. b- Liver Integrity And Secondary Nephropathy Elevated Significantly Sera Glucose And Albumin Mean Values. c- Oxidative Stress Biomarkers Lowered Hepatic MDA Mean Value Significantly. The Hepatic GSH Mean Value Was Significantly Elevated And Was Normalized. The GST Mean Value Was Significantly Decreased. d- Lipid Profile Significantly Reduced Leptin Mean Value. e- Liver Histopathology Improved Liver Histopathology And Preserved Normal Hepatic Architecture. 2-Effect Of Daily Oral Administration Of Resveratrol On The a- Degree Of Fatty Liver Steatosis And Hepatic Injury Significantly Lowered TNF-Α And Liver Function ALT Mean Values. b- Liver Integrity And Secondary Nephropathy Significantly Lowered Serum Glucose Mean Value While Serum Albumin Mean Value Was Elevated. c- Oxidative Stress Biomarkers Significantly Elevated And Normalized Hepatic GSH Mean Value. d- Lipid Profile Significantly Reduced Leptin Mean Value. e- Liver Histopathology Improved Liver Histopathology Showing Normal Hepatocytes With Preserved Hepatic Architecture And Slightly Congested Hepatic Sinusoids Still Noticed. 3- Effect Of Daily Oral Administration Of N-Acetyl Cysteine On The a- Degree Of Fatty Liver Steatosis And Hepatic Injury Significantly Lowered TNF-Α And Liver Function ALT Mean Values. On The Other Hand, AST Mean Value Was Significantly Elevated. b- Liver Integrity And Secondary Nephropathy Significantly Lowered Serum Glucose Mean Value. On The Other Hand, Serum Albumin Mean Value Was Significantly Elevated. c- Oxidative Stress Biomarkers Significantly Lowered Hepatic MDA And Hepatic GST Mean Values While Hepatic GSH Mean Value Was Significantly Elevated. d- Lipid Profile Significantly Reduced Serum TC, TG, LDL-C And Serum Leptin Mean Values. e- Liver Histopathology Improved Liver Histopathology Showing Congested Central Vein And Slightly Dilated Congested Hepatic Sinusoids With Activated Von Kupffer Cells. II. Protective Model Of Steatosis 1-Effect Of Daily Oral Administration Of Ursodeoxycholic Acid On The a- Degree Of Fatty Liver Steatosis And Hepatic Injury Normalized The Liver Index Mean Value While TNF-Α And Liver Function ALT Mean Values Were Significantly Decreased. b- Liver Integrity And Secondary Nephropathy Significantly Decreased Serum Glucose Mean Value Till Normalization While Serum Albumin Mean Value Significantly Increased. c- Oxidative Stress Biomarkers Significantly Decreased Hepatic MDA And Hepatic GST Mean Values But Only Hepatic MDA Was Normalized. Hepatic GSH Content Was Significantly Elevated. d- Lipid Profile Significantly Lowered Serum Leptin Mean Value. e- Liver Histopathology Caused Improvement In Liver Histopathology where Normal Hepatic Architecture Was Preserved With Normal Hepatocytes, Hepatic Sinusoids Showing Minimal Congestion And Slightly Dilated Central Vein. 2-Effect Of Daily Oral Administration Of Resveratrol On The a- Degree Of Fatty Liver Steatosis And Hepatic Injury Resulted In A Liver Index Mean Value That Was Significantly Elevated Till Normalization. Serum TNF-Α And Liver Function Serum ALT Mean Values Were Significantly Decreased. b- Liver Integrity And Secondary Nephropathy Significantly Decreased Serum Glucose Mean Value Till Normalization And Significantly Elevated Serum Albumin Mean Value. c- Oxidative Stress Biomarkers Caused A Significant Decrease In Hepatic MDA And Hepatic GST Mean Values Till Normalization In The Case Of Hepatic MDA Only. Hepatic GSH Content Was Significantly Increased. d- Lipid Profile Resulted In Serum TC And LDL-C Mean Values Significant Decrease While Serum HDL-C Mean Value Was Normalized. Serum Leptin Mean Value Was Significantly Lowered. e- Liver Histopathology Showed Liver Histopathological Improvement With Normal Hepatocytes With Preserved Hepatic Architecture. Hepatic Sinusoids Showed Slight Congestion, Dilatation And There Was Slight Von Kupffer Cell Activation Noticed. 3-Effect Of Daily Oral Administration Of N-Acetyl Cysteine On The a- Degree Of Fatty Liver Steatosis And Hepatic Injury Significantly Lowered Serum TNF-Α And Liver Function Serum ALT Mean Values. b- Liver Integrity And Secondary Nephropathy Resulted In A Significant Decrease In Serum Glucose Mean Value And A Significant Increase In Serum Albumin Mean Value. c- Oxidative Stress Biomarkers Significantly Decreased Hepatic MDA And Hepatic GST Mean Values While Hepatic GSH Mean Value Was Significantly Increased. d- Lipid Profile Significantly Decreased Serums TC, TG, LDL-C, VLDL-C And Leptin Mean Values. e- Liver Histopathology Revealed Liver Sections Showing Congested Central Vein With Congested And Slightly Dilated Hepatic Sinusoids. Hepatocytes Were Seen Normal With Preserved Hepatic Architecture. Based On These Results It Could Be Concluded That 1- Fatty Liver Induction Caused Liver Insults Through Oxidative Stress And Release Of Inflammatory Mediators. 2. Ursodeoxycholic Acid, Resveratrol And N- Acetylcysteine Exhibited Good Protection Of The Liver Against The Successive Periods Of Feeding A MCDD And Fasting. 3. These Hepatoprotective Effects Were Stipulated By Their Antioxidant And Metabolic Processes Controlling By Normalizing Back Properties Of Liver Membranes And Membranous Proteins. 4. These Herbal Test Agents Could Be Used Either To Prevent Or Protect The Liver Against Various Liver Injuries And Insults. It Is Advised To Proceed With Clinical Trials To Further Prove These Claims. Recommendations 1- Always Work On Having A Healthy Weight Through Diet And Exercise. 2- Foods That Should Have A Place In Daily Diets Include Those That Fight Cell Damage, Help The Body In Secreting And Utilizing Insulin Easily Or Lower Any Inflammation Assisting The Body In Reversing NAFLD. 3- Every Person Is Different So Not Every Diet Is Generalized For Every Patient With NAFLD. Following Up With A Dietician To Find The Best Eating Plan That Works Right Is Important. 4- Foods That Help Reducing Fat In The Liver Include Healthy Fats Such As Omega-3 Fatty Acids Found In Fish, Vegetable Oils And Leafy Plants. Also Monounsaturated Fats Found In Nuts, Avocados, Olive Oil And Several Other Plants Are Good Sources Of Healthy Fat. Saturated Fats Are Harmful So Must Be Avoided As Much As Possible. 5- Eating Lower Amounts Of Meat And Dairy Products While Avoiding Baked Goods And Fried Foods Made With Palm Or Coconut Oils Helps Decrease Fatty Deposits In The Liver. 6- Fruits, Especially All Sorts Of Berries, Vegetables And Some Other Foods Have Antioxidants That Are Rich In Vitamins Such As C And E Having A Good Cholesterol-Lowering Effect. 7- Scientists Have New Information On What Happens At The Molecular Level When We Go Hungry. They Were Able To Show That Upon Fasting A Certain Protein Is Produced That Adjusts The Metabolism In The Liver So Fasting Is A Vital Key In Restoring The Liver Back from NAFLD And NASH. |