American Journal of Medicine and Medical Sciences 2016, 6(3): 98-116 DOI: 10.5923/j.ajmms.20160603.07 Histological and Immunohistochemical Study on the Possible Protective Effect of Olive Leaves Extract on Mitochondrial Changes of the Proximal Convoluted Tubule in Diabetic Male Albino Rats Mervat Shaker Mehanna, Fatma Sayed Abdel Aal * , Dina Allam Abdel Maksod, Marwa Kamal Taha Histology Department, Faculty of Medicine (for girls), Al-Azhar University, Egypt Abstract Damaged or dysfunctional mitochondria by hyperglycemia generate excessive reactive oxygen species (ROS) such as superoxide anion, O−2 and hydrogen peroxide, H2O2- which is the primary initiating all other pathways of tissue damage. This study aims to investigate the histologicalchanges in the mitochondria of the proximal convoluted tubules of the kidney in diabetic and treated adult male albino rat with insulin, olive leave extract (OLE), and combined therapy of both of them. In this work five groups of rats (n=6 in each group) was used.GI (Control group): received sodium citrate buffer pH4.5 once. GII (Diabetic group): the animal received STZsingle dose. GIII (Diabetic, insulin treated group): diabetic rats of this group were daily treated with insulin for 9 weeks. GIV (Diabetic, aqueous OLE treated group): diabetic rats of this group were daily treated with aqueous OLE for 9 weeks. GV (Diabetic, insulin and aqueous OLE treated group): diabetic rats of this group were daily treated with insulin and aqueous OLE for 9 weeks: Fasting plasma glucose level, serum creatinine, and blood urea nitrogen were evaluated in blood samples from all rats of all groups and statistically analysed. At the end of the experiment both kidney processed for light and electron microscopic examination. The results revealed, examination of the proximal convoluted tubules of GII demonstrated that the cells lining convoluted tubules revealed thick basement membranes, disorganization of basal infolding, and mitochondrial changes. The area% of positive Bax immunoreactions was significantly increased in GII as compared with GI. These changes were relatively reduced in treated groups. We concolude that combined therapy of insulin and OLE provide better glycaemic control and protection for the ultrastructure of PCT with better kidney function glycemic control and protection for the ultrastructure of PCT with better kidney function tests. Keywords Diabetes mellitus, Structure kidney, Mitochondria, Olive leave extract 1. Introduction Diabetes mellitus (DM) is a metabolic disorder which arises from complex interactions between multiple genetic and environmental or lifestyle factors. This chronic disease is characterized by the presence of hyperglycemia due to defective insulin secretion, insulin receptors, or both. The two major forms of the diabetic syndrome are, type I diabetes (TID), and, type II diabetes (TIID). The majorities (90% of patients) with diabetes have TIID [1]. Diabetic nephropathy (DN) develops in a large number of TID and TIID patients after a variable latency period [2]. The pathogenesis of DN is clearly multi-factorial as several genes, proteins and environmental factors are likely to contribute to * Corresponding author: Fatma_baker2001.@yahoo.com (Fatma Sayed Abdel Aal) Published online at http://journal.sapub.org/ajmms Copyright © 2016 Scientific & Academic Publishing. All Rights Reserved the onset of the disease [3]. Previously, DN was described as a glomerulopathy associated with diffuse or nodular glomerulosclerosis, although less than one-third of diabetic patients have this type of glomerulopathy, while, tubular functional and structural changes correlate better with DN progression, and may be the key to development of kidney dysfunction in diabetes [4]; [5]. Damaged or dysfunctional mitochondria by hyperglycemia generate excessive reactive oxygen species (ROS)-e.g. superoxide anion, O − 2 andhydrogen peroxide, H 2 O 2 - which is the primary initiating event that activates all other pathways of tissue damage [6] Interestingly, according to one estimate the steady state concentration of O 2 − in the mitochondrial matrix is about 5 to 10 fold higher than that in the cytosol or nucleus [7]. [8]; [9] added that ROS nowadays believed to be second messenger supported by the important role they mediate in several biologic responses such as proliferation, extracellular matrix deposition (ECM)