Effect of oralistat (antiobesity drug)on rat submandibular salivary gland (histological and ultrastructural study)
Farag, Dina Badawy El Said
Abbas, Mohamed Gad
Ezzat, Bassant Adel
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The present study was performed to investigate the effect of antiobesity drug orlistat on the rat submandibular salivary glands using histological and ultrastructural techniques. Statistical analysis was also performed to monitor changes occurred in animal’s body weights during the experiment. The experiment was done on thirty healthy adult male albino rats. The animals were divided into three groups as follows: 1- Control group (group I): This group received their diet contained ground barley and drank water adlibitum. 2- Experimental group (group II): This group received the above mentioned diet contained 200 mg orlistat / kg barley for 15 days. 3- Experimental group (group III): This group received the control diet containing 200 mg orlistat / kg barley for 45 days. The average body weight for each animal was calculated every week till the end of the experiment. At the end of the experiment the animals were scarified. The submandibular salivary glands of both sides were dissected and separated. In all groups the specimens of one side were immediately fixed in 10 % calcium formol, dehydrated in alcohol, cleared in xylol, embedded in paraffin wax, sectioned and stained with Hx. and E. for histological examination. The specimens of the other side in the control and experimental group III were processed for electron microscopic examination, small pieces of average size 1mm³ were cut and fixed for primary fixation in 3% phosphate buffered glutraldhyde then post fixation, dehydration and embedding in oven dried gelatin capsules took place. Then semithin sections were cut and stained to be examined with light microscope. Afterwards, ultrathin sections were cut, mounted on copper grids and stained for final examination by transmission electron microscope. The present investigation revealed the following results: - Statistical analysis of percentage increase in body weights among the investigated animals revealed non significant difference among control and experimental groups (II and III). - Histological examination of submandibular salivary gland of group II revealed mild degenerative changes as loss of acinar architecture and intracytoplasmic vacuolization. Also the ducts showed stagnant secretion in their lumen. Few red corpuscles were dispersed between the acini and the ducts. - In group III more marked atrophic changes were demonstrated as there were extensive intracytoplasmic vacuolization, also some secretory cells were degenerated and their nuclei lost completely leaving homogenous eosinophilic degenerative material. - The granular convoluted tubules showed decrease in their eosinophilic granules. The striated and excretory ducts demonstrated rupture in their cell membrane with subtotal loss of their cytoplasmic content. - The blood vessels were markedly dilated and sometimes ruptured with extravasations of red blood corpuscles within the gland. - The examination of semithin sections of submandibular salivary gland of group III showed widening of intercellular spaces, intracytoplasmic vacuolization and clear loss of zymogen granules. Also the nuclei were darkly stained. - Electron microscopic findings in submandibular salivary gland of group III added to the structural results. There was loss of cellular contacts accompanied by different degree of cellular degeneration. Karyorrhexis (clumping of chromatin), margination and segregation of chromatin were found. Loss of continuity of nuclear membrane and widening of the nuclear pores as well as intracytoplasmic and intranuclear vacuoles were also observed. The secretory granules appeared to be fused into large vacuoles. - Dilated rough endoplasmic reticulum and swollen degenerated mitochondria were also frequently detected in the submandibular salivary gland of group III as well as lysosomes and myelin figures. - The outstanding ultrastructural feature in experimental group III was the presence of dilated blood vessel studded with blood in dissociated connective tissue. Other blood vessels appeared with ruptured endothelium and other showed sinusoidal endothelial lining causing collapse of their lumen. In the present study the following conclusions could be reached: 1- Orlistat administration for a period of 15 days leads to mild changes in the submandibular salivary gland. 2- Administration of orlistat for longer period 45 days caused more aggravated changes manifested as degeneration and vacuolization of cells leading to possible deterioration of the functions of submandibular salivary gland. 3- Accordingly, we recommend that patients undergoing orlistat therapy should be aware of their oral hygiene and should be subjected to periodic oral and dental care. 4- We recommend those patients to take fat soluble vitamins supplements to overcome the impairment in their absorption that induced by orlistat, as malabsorption of those vitamins leads to negative effects on both the tissues and health.