الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Tuberculosis (TB) is one of the oldest and persistent, respiratory spreading disease. Anti-tubercular drugs can be divided into two major categories; first line anti-tubercular drugs which include isoniazid (INH) and rifampicin (RIF), and second line anti-Tb drug which include thioamides and aminoglycosides. The drug toxicity is another problem in tuberculosis treatment, INH and RIF caused hepatotoxicity and nephrotoxicity. The present study has been conducted to evaluate the protective role of prunus armeniaca and simmondsia chinensis on anti-tubercular drugs induced hepatotoxicity and nephrotoxicity.
Animals were divided in to seven groups. These groups were sacrified at the end of 6 weeks. The experimental groups were designated as follows:
group 1: This group was regarded as normal group and was kept without treatment and given C.M.C under the same laboratory conditions daily for 6 weeks.
group 2: Served as control untreated rats administered with [50 mg/kg Isoniazid + 50 mg/kg Rifampicin] for 6 weeks Isoniazid and Rifampicin solutions were dissolved in sterile distilled water. The pH of Rifampicin solution was adjusted to 3.0 with 0.1 mol/L HCl Isoniazid and Rifampicin were administered orally daily for 6 weeks.
group 3: The rats of this group were administered with (50 mg/kg Isoniazid + 50 mg/kg Rifampicin +100 mg/kg Prunus armeniaca leaf extract) extraction of Prunus armeniaca was dissolved in carboxy methyl cellouse solution 1% orally for 6 weeks.
group 4: The rats of this group were administered with (50 mg/kg Isoniazid + 50 mg/kg Rifampicin +200 mg/kg Prunus armeniaca leaf extract) extraction of Prunus armeniaca was dissolved in carboxy methyl cellouse solution 1% orally for 6 weeks.
group 5: The rats included in this group were administered with (50 mg/kg Isoniazid + 50 mg/kg Rifampicin +100 mg/kg Simmondsia chinensis leaf extract) extraction of Simmondsia chinensis was dissolved in carboxy methyl cellouse solution 1% orally for 6 weeks.
group 6: The rats included in this group were administered with (50 mg/kg Isoniazid + 50 mg/kg Rifampicin +200 mg/kg Simmondsia chinensis leaf extract) extraction of Simmondsia chinensis was dissolved in carboxy methyl cellouse solution 1% orally for 6 weeks.
group 7: The rats included in this group were administered with (50 mg/kg Isoniazid + 50 mg/kg Rifampicin +50 mg/kg silymarin) extraction of silymarin was dissolved in carboxy methyl cellouse solution 1% orally for 6 weeks.
The dosage was adjusted every week according to any change in body weight to maintain similar dose per kg body weight of rat over the entire period of study for each group.
By the end of the experimental period, fasted rats in all groups were sacrificed under diethyl ether anaethesia. Blood samples were collected from each rat, left to coagulate, then centrifuged and the clear supernatant sera were quickly removed for subsequent biochemical analysis for liver functions that include (AST, ALT, ALP, GGT, total bilirubin, total protein, albumin, globulin and albumin/globulin ratio), kidney functions that include (urea, uric acid and creatinine), adiponectin and pro-inflammatory cytokine (TNF-α) and (IL-1β). Kidney and liver tissues were quickely excised after dissection of the animals. Fresh Kidney and liver tissue samples were immediately removed from each animal and cut into two pieces one of them was fixed in 10% neutral buffered formalin for examined through the electric light microscope. The other part of these tissues were homogenized for determination of glutathione (GSH) content, lipid peroxidation (LPO) and activity of antioxidant enzyme including glutathione peroxidase (GPX) and superoxide dismutase (SOD).
Results showed that INH and RIF caused a marked elevation in the activities of serum enzymes of liver function (AST, ALT, ALP, GGT, total bilirubin and albumin/globulin ratio) together with a decrease in total protein, albumin, globulin and adiponectin concentration. Also, INH and RIF caused a marked elevation in kidney function parameters, TNF-α and IL-1β.
These biochemical changes of anti-tubercular drugs administered rats are confirmed by histopathological alterations in liver in which diffuse fatty changes, dilatation and congestion in both central and portal veins as well as inflammatory cells infiltration in the portal area. Also, anti-tubercular drugs induced nephrotoxicity was evidenced by histological changes including the glomerular tuft showed swelling and proliferation in the lining endothelium while the Bowman’s capsule had swelling in the lining epithelial cells. The treatment of these animals with prunus armeniaca and simmondsia chinensis successfully prevented most of these biochemical and histopathological alterations.
The treatment with prunus armeniaca and simmondsia chinensis remarkably improved the deleterious effect of INH and RIF on oxidative stress and antioxidant defense system. This amelioration was reflected by increase of glutathione, glutathione peroxidase and super oxide dismutase and decrease in lipid peroxidation.
Taken these data together, it can be concluded that prunus armeniaca and simmondsia chinensis could protect liver and kidney against anti-tubercular drugs induced hepato-nephrotoxicity. The hepatic glutathione content and antioxidant activities may play a central role in the hepato-nephro protection against anti-tubercular drugs induced toxicity.