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SummaryAlternative medicine is the hope of medical professionals and patients to stop using drugs and chemicals, which cause a burden on the liver to do metabolism and detoxify these agents. Herbal medicine is one of the branches of the alternative medicine, which is widely used in last years to deal with many diseases.Fruits of schisandra have been traditionally used in China for the treatment of dyspnea, cough, mouth dryness, spontaneous diaphoresis, nocturnal diaphoresis, nocturnal enuresis, dysentery, insomnia and amnesia.Nigella Sativa seeds have been widely used in traditional medicine as diuretic, antihypertensive, liver tonic, digestive, emmenagogue, analgesic, antihelmintic, anti-bacterial, and useful in skin disorders. It also has been extensively studied for its biological activities and has been shown to be anti-diabetic, anticancer, immunomodulator, spasmolytic, bronchodilator, hepatoprotective and renal protective due to its antioxidant properties.In this work, we studied the carbon tetrachloride-induced hepatotoxicity by evaluation of liver function tests (AST, ALT and total bilirubin) and serum malondialdehyde. Liver tissue was subjected to histopathological examination using the routine Haematoxylin and Eosin stain.DDB and N.S.oil were used to counteract CCl4-induced hepato- toxicity and to compare between them to know which one is more effective in improvement and protection against CCl4-induced liver damage.Seven groups(four control groups and three treated groups) of adult albino rats of both sexes were subjected to this study as follow:Group I: 20 rats were served as negative control group (with free access to normal diet and tap water) ad-liptum.Group II: 20 rats, each rat was gavaged with corn oil at a dose of (2 ml/kg) once daily for 8 weeks.Group III: 20 rats, each rat was gavaged with DDB at a dose of (160 mg/kg) once daily for 8 weeks.Group IV: 20 rats, each rat was gavaged with N.S. oil at a dose of (800 mg/kg) once daily for 8 weeks.Group V: 60 rats, each was gavaged with CCl4 at a dose of (2 ml/kg) once daily for 4 weeks.At the end of the 4th week, blood samples were collected from group Va(20 rats) to detect liver functions and MDA and then the animals were sacrificed, liver specimens were taken and subjected to histopathological examination then, the remaining 40 rats of group V were divided into 2 groups:Vb: 20 rats, each rat was gavaged with DDB at a dose of (160 mg/kg) once daily for another 4 weeks(therapeutic group).Vc: 20 rats were gavaged with N.S. oil at a dose of (800 mg/kg) once daily for another 4 weeks(therapeutic group).Group VI: 20 rats, each rat gavaged with DDB at a dose of (160 mg/kg) once daily one hour before each dose of CCl4 (2ml/kg) for 8 weeks(protected group).Group VII: 20 rats, each rat gavaged with N.S.oil at a dose of (800mg/kg) once daily one hour before each dose of CCl4 (2ml/kg) for 8 weeks(protected group).In the remaining groups at the end of the 8th week, blood samples were collected from retro-orbital plexus to measure the serum level of AST, ALT, total bilirubin and malondialdehyde. Then, rats were sacrificed for histopathological examination of the liver.The results after being tabulated and statistically analyzed revealed that elevation in AST, ALT, total bilirubin and malondialdehyde were evident in CCl4 group. This elevation was accompanied with histopathological changes in form of hepatic inflammation, hydropic degeneration, fatty changes, necrosis and fibrosis.In DDB therapeutic group(Vb) and N.S.oil therapeutic group(Vc), there were significant reduction of the elevated enzymes when compared with CCl4 treated group(Va) and this accompanied by improvement of the toxic hepatopathy. The improvement in AST was more prominent with DDB therapeutic group(Vb) than N.S.oil therapeutic group(Vc), while the improvement in ALT was more prominent with N.S.oil therapeutic group(Vc) than DDB therapeutic group(Vb).As regard T.bilirubin and MDA there were non significant differences between both DDB and N.S.oil therapeutic groups(Vb &Vc).The histopathological improvement was more evident with N.S.oil therapeutic group(Vc) than DDB therapeutic group(Vb).In DDB protected group(VI) and N.S.oil protected group(VII), there were significant reduction in elevated enzymes when compared with CCl4 treated group(Va) and this accompanied by slight improvement in histopathological changes. The improvement in serum AST, ALT and MDA were more prominent with N.S.oil protected group(VII) than DDB protected group(VI).As regard T.bilirubin there was non significant difference between both DDB and N.S.oil protected groups(VI &VII).The histopathological improvement was non-significant as comparing both groups VI and VII.ConclusionThe hepatotoxicity induced by CCl4 is proved to be due to oxidative stress and LPO that cause hepatocellular necrosis and elevation of liver enzymes(AST, ALT), T. bilirubin and serum MDA.Both DDB and N.S.oil have significant improvement effects on CCl4 induced hepatotoxicity.The effectiveness of N.S.oil is better than DDB in both therapeutic and protective maneuver.The therapeutic maneuver in both N.S.oil and DDB is better in reduction of hepatotoxicity induced by CCl4 than protective maneuver.Recommendations(1) CCl4 usage should be really restricted all over the world.(2) Improvement of health educational programs to increase the population and workers awareness about the hazards resulting from CCl4 usage.(3) Periodic monitoring of liver functions for workers who still work in CCl4 industries.(4) Workers at CCl4 industries who have impaired liver functions should be stop working and supplemented with antioxidants like N.S.oil or DDB until their improvement, then after their return to the work maintained supplementation by N.S.oil or DDB are recommended.(5) Further studies are recommended to evaluate the protective role of combined DDB- N.S.oil and other antioxidants.(6) Further studies are recommended to evaluate the effectiveness of both DDB and N.S.oil against other hepatotoxic agents.
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