SU M M A R Y A ND C O N C L USI O NS Carbon tetrachloride (CCl4) is a haloalkane used in a variety of industrial and chemical applications. It is relatively stable environmental contaminant which can occur in air, water and food. Carbon tetrachloride is extensively used in industry as an organic solvent and is known to be hepatotoxin in several species of animals and humans. Salvia officinalis (commonly known as sage) is an aromatic plant belonging to the family Lamiaceae. Several species of Salvia are cultivated for their aromatic characteristics and are used as flavorings, food condiments, cosmetics and perfume additives. Additionally, Salvia species have commonly been widely used as folk medicines as antibacterial, antiviral, antitumor, spasmolytic, antioxidant and antiinflammatory treatments and have further been used in the treatment of mental, nervous and gastrointestinal conditions. The analysis of leaf extract showed that it contains several important compounds such as flavonoids, terpenoids, phenols, vitamins and alkaloids. All these compounds are well documented as free radical scavengers. The present work was designed to investigate the protective role of water extract of S. officinalis against hepatotoxicity disorders in different haematological parameters induced by CCl4 in male Swiss albino mice. To achieve such purpose the present work was planned to: 1- Study the protective effect of Salvia officinalis against the histopathological changes induced by CCl4 in liver tissue of Swiss albino mice. 2- Study the protective effect of Salvia officinalis against the ultrastructure changes induced by CCl4 in liver tissue of Swiss albino mice. 3- Study the protective effect of Salvia officinalis against physiological disorders in the liver function of Swiss albino mice. 4- Study the antioxidant potential of Salvia officinalis against the physiological disorders caused by CCl4 in different haematological parameters.! ! ""##! In the present investigation, the animals were divided into 5 groups of 20 animals each and treated as follows: Group I: Animals in this group received 10 ml/kg b.w. normal saline (0.9% NaCl) every other day for four successive weeks and served as a negative control. Group II: Each animal in this group was orally given olive oil at a dose level of 10 ml/kg b.w. every other day for four successive weeks and served as a positive control (vehicle). Group III: Each mouse was orally received sa lvia extract at a dose level of 10 ml/kg b.w every other day for four successive weeks. Group IV: Each animal was orally given CCl4 dissolved in olive oil at a dose level of 1.9 ml/kg b.w. (! LD50, Essawy et a l.2010) every other day for four successive weeks. Group V: Each mouse was orally received Saliva extract at a dose level of 10ml/kg b.w. every other day alternated with CCl4 at a dose level of 1.9 ml/kg b.w. (! LD50) for four successive weeks. After two and four weeks of treatment, blood samples were collected for haematological and biochemical investigations. Also, samples of liver from control and treated animals were removed and prepared for histological and ultrastructure studies. Results obtained during the course of this study can be summarized as follows: 1- Results of examination of haematological parameters Ɣ 2UDO DGPLQLVWUDWLRQ RI ó /'50 CCl4 for two & four weeks led to microcytic K\SRFKURPLF DQHPLD ZKLFK ZDV FKDUDFWHUL]HG E\ GHFUHDVH LQ WKH YDOXHV RI 5%&¶V count, Hb, PCV, MCV and MCH. Treatment with ! LD50 of CCl4 induced also significant decrease in total WBC (marked leucopaenia). These changes were time dependant. Ɣ7UHDWPHQWZLWK&&O4 resulted in neutropaenia (significant decrease in neutrophils) and significant increase in lymphocytes and monocytes. Ɣ7UHDWPHQWZLWK&&O4 induced decrease in platelets count.! ! ""#""! Ɣ$QLPSURYHPHQWLQDOOKDHPDWRORJLFDOSDUDPHWHUVDVZHOODVLQSODWHOHWVFRXQWDQGLQ the percentage of neutrophils, lymphocytes and monocytes was detected in mice treated with CCl4 plus S. officinalis comparing to animals treated with CCl4 alone. 2- Results of Biochemical analysis: Ɣ 7UHDWLQJ DQLPDOV ZLWK &&/4 for two or four weeks induced significant elevation in AST, ALT, ALP and LDH when compared to normal control mice Ɣ7UHDWLQJDQLPDOVZLWK&&/4 plus the aqueous leaf extract of S. officinalis improved the elevated activities in the liver enzymes AST, ALT, ALP and LDH. 3- Results of histological examination: Ɣ$QLPDOVtreated with ! LD50 of CCl4 revealed many histopathological alterations in the liver e.g. destruction of liver architecture, congestion of blood vessels, damaged blood sinusoids, leucocytic infilteration, cytoplasmic vacuolization of hepatocytes and karyolytic nuclei. These alterations were more severe and pronounced in animals treated with CCL4 for four weeks. Ɣ $GPLQLVWUDWLRQ RI S. officinalis improved most of the previously mentioned histological alterations. The liver tissue restored most of its normal structure, but some hepatocytes appeared with cytoplasmic vacuoles and few areas of leucocytic infilteration were noticed. 4- Results of ultrastructure study: Ɣ 7UHDWPHQW ZLWK &&O4 for four weeks induced several ultrastructure abnormalities including both the nucleus and the cytoplasm. The cytoplasm lacked its compartimentation and appeared to be necrotic and almost devoid of its components. Cisternae of rough endoplasmic reticulum were highly fragmented, but some hepatocytes showed proliferated and dilated rough endoplasmic reticulum with loss of ribosomes. Deformed or dameged mitochondria and accumulated lipid droplets were recorded.! ! "" Damaged blood sinusoids with deformed endothelial cells, hypertrophoid abnormal Kupffer cells and bile canaliculi with degenerated and fragmented microvilli were also observed. ƔAdministration of S. officinalis improved most of the previously mentioned cytological alterations in hepatocytes and lessened the number of cells with severe abnormalities.