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Efficacy of different medical herbal preparations as hepatoprotective agents
Abstracts / Toxicology Letters 164S (2006) S1–S324
P26-18 Safety and therapeutic efficacy of UC-II alone or in combination with Glucosamine + Chondroitin in arthritic dogs R.C. Gupta 1 , M. D’Altilio 1 , A. Curtsinger 1 , T.D. Canerdy 1 , J.T. Goad 1 , M. Bagchi 2 , D. Bagchi 2 1 Murray
USA;
State University, Hopkinsville/Murray, KY,
2 InterHealth Research Center, Benicia, CA, USA
Arthritis in large breed dogs is as common as in humans. Arthritis is closely associated with obesity. Obese arthritic dogs were treated with selected combinations of three supplements including glycosylated type-II collagen (UC-II), Glucosamine HCl (GLU), and Chondroitin sulfate (CH). Dogs were daily supplemented with either placebo (Gr-I), 10 mg UC-II (Gr-II), 2000 mg GLU + 1600 mg CH (Gr-III), or UC-II + GLU + CH (GrIV) for 120 days, followed by a 30-day withdrawal. Dogs were examined on a monthly basis for overall pain, pain upon limb manipulation, and exercise-associated lameness. Gr-I exhibited no improvement. Gr-II showed significant reductions in pain within 30–60 day of treatment. Maximum pain reductions were noted after 120 day (overall pain, 62%; pain upon limb manipulation, 91%; and exercise-associated lameness, 78%). Gr-III dogs showed some pain alleviation, while Gr-IV exhibited marked reductions (57%, 53%, and 60%, respectively). 30-Day withdrawal led to pain relapse in all dogs. Serum samples were analyzed for markers of liver function (bilirubin and ALT), renal and heart function (BUN, creatinine and CK). Body weight and temperature were measured. Serum chemistry, body weight and temperature remain unchanged. Thus, daily treatment of arthritic dogs with UC-II alone or in combination with GLU + CH significantly ameliorates the signs of arthritis, and supplements used in the present study are safe and well tolerated without any side effects. doi:10.1016/j.toxlet.2006.07.311 P26-19 Drug analyses of necrophagous insects and human tissues Marija Definis-Gojanovic, Davorka Kokan, Bogomir Milosevic
Sutlovic, Bozo
University Hospital Split, Split, Croatia Necrophagous insects may provide useful information concerning the time, place and cause of death. In addition, they can serve as reliable alternate specimens for toxicological analyses in the cases when human tissues
S311
and fluids, normally taken during autopsies, are absent due to decomposition of the corpses. This paper reports the results of drug analyses of the developmental stages of two flies species (Calliphoridae and Sarcophagidae), collected from the body of middleage man who had committed suicide approximately 3 weeks prior his corpse was found. Analyses of multiple samples (human tissues and maggots) were performed using a gas chromatography–mass spectrography, and amphetamine was detected in all samples. While the qualitative relationship of the results was without any doubt, the quantitative results were less clear and further research in this area is suggested. doi:10.1016/j.toxlet.2006.07.312 P26-20 Efficacy of different medical herbal preparations as hepatoprotective agents Mohey M. Ellithy, Somaia A. Nada Pharmacology Department, National Research Centre, P.O. 12622 Dokki, Cairo, Egypt In folk medicine, there are many herbal preparations have been used for their hepatoprotective activities. One of the most common recipes contain from equal parts (w/w) of decoction of (10% concentration): Peumus boldus (leaves), Cichorium intybus (root) and Nigella sativa (seed) (Recipe 1). Glycyrrhazia rhizome (root) was replaced with Cichorium intybus (Recipe 2) or added (Recipe 3). Three groups of normal albino rat were orally administrated 1.5 ml/100 g of Recipe 1 (group 1), Recipe 2 (group 2) or Recipe 3 (group 3) and the control group (group 4) was given 1.5 ml/100 g distilled water daily for 30 successive days. Results for normal groups revealed that Recipe 1, 2 and 3 were decreased plasma ␥glutamyl transferase (GGT): −6.1%, −26.7%, −31.5%; ALT: −3.8%, −13.2%, 17.6%; AST: −5.9%, −6.8%, −21.5%; triglycerides: 1.8%, 0%, −13%; cholesterol: −2.4%, −1.2%, −1.9% and sleeping time: 0.5%, 1.4%, 0.9%, respectively, versus control values. Second set of experiment, four groups of carbon tetrachloride-hepatic damaged rats were given the three recipes with the same above oral doses before carbon tetrachloride for 2 weeks, then followed by another 2 weeks after induction of the hepatic damage. The results indicated that significant decrease in GGT: −70%, −74.5%, −82.0%; ALT: −30.1%, −36.8%, −49.0%; AST: −9.9%, −33.3%, −43.8%; triglycerides: −11.8%, −10.5%, −17.0%; cholesterol: −17.4%, −16.4%, −24.4% and sleeping time: −24.0%, −25.1%, −37.9%, respectively, versus carbon tetrachloride-hepatic dam-
S312
Abstracts / Toxicology Letters 164S (2006) S1–S324
aged rats .In conclusion: the modified Recipe 3 was found to be more potent than Recipe 1 or 2. doi:10.1016/j.toxlet.2006.07.313 P26-21 HPLC method for methadone quantification in biological samples Anne-Marie Ciobanu, Daniela Luiza Baconi, Maria Barca, Dan Balalau, Mihaela Ilie, Ivonne Pencu University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania The use of methadone in substitution treatment of opiate addict patients is well documented. Clinical success in the methadone substitution treatment depends on the methadone suitable doses to maintain blood levels in the pharmacologically effective range. Many study highlighted the insufficient methadone dose as a major cause of the treatment failure. Several evidences exist supporting a relationship between methadone dosage and plasma methadone concentration in addicted patients during substitution therapy. We present a sensitive reversed-phase HPLC method for methadone quantification in plasma. Several HPLC columns have been tested and a RP-18, 125 cm × 0.46 cm (i.d.) packed with 5 m diameter particles has been selected. As a mobile phase, 0.1 trifluoroacetic acid–methanol (60:40, v/v), has been used. Methadone was detected at 210 nm. Linear relationships between peak area and methadone concentrations were obtained in the range of 0.0275–0.22 g/mL. The method has been validated for determination of plasma concentration of methadone. A liquid–liquid extraction procedure has been applied. The method is precise and accurate (mean recovery percent 92.34%), with a LOQ of 2.5 ng/mL. The developed method was applied to monitoring methadone plasma levels in heroin addicts patients, during methadone substitution treatment conducted at Sf. Stelian Center for Evaluation and Treatment of Addictions, Bucharest. Considerable inter-individual variations of methadone plasma concentrations have been demonstrated. doi:10.1016/j.toxlet.2006.07.314
P26-22 Toxic affects of HCG on the distribution pattern of mature rat uterine surface glycoconjugates during implantation period Aliabadi Elham, Talaii khozani Tahereh, Mesbah ardekani seyed Fakhredin, Makoolati Zohreh Department of Anatomy, Medical School, Shiraz University of Medical Science, Iran Introduction: Unovulatory period is one of the most causes of infertility .One of the treatment to such cases is hormone therapy. These hormones may have toxic affect on the molecular organization of uterine surface e.g. glycoconjugates. Glycoconjugates are one of the most important molecules of the uterine surface which play an important role in embryo implantation. In this study, the toxic effects of one of these gonadotropin hormones, Human Chorionic Gonadotropin (HCG), on glycoconjugates of uterine surface (apical membrane, Golgi zone and basement membrane of rat endometrial cells and uterine glands) during implantation period were studied. Material and method: Sixteen mature female rat was selected and divided to two groups (experimental and control groups). Experimental rats injected with 10 IU HCG intraperitoneally in estrus phase and mated with proven fertile male rats. The observation of vaginal plug was considered as 0.5 day of pregnancy. The rats were sacrificed at 5.5 day of pregnancy (time of implantation) and their uteruses were removed. Control rats become pregnant without any injection. The pregnant uterine tissues were fixed in bouin solution and embedded in wax. Lectin histochemistry was done with use of WGA, DBA, PNA, ConA, SBA and UEA lectins. Results: The intensity of the reaction to WGA in apical membrane, Golgi zone and uterine gland and the reaction of uterine gland to DBA and UEA were significantly low in experimental groups. Conclusion: HCG can induce its indirectly toxic effects on implantation rate via changes in uterine surface glycoconjugates. doi:10.1016/j.toxlet.2006.07.315
P26-18 Safety and therapeutic efficacy of UC-II alone or in combination with Glucosamine + Chondroitin in arthritic dogs R.C. Gupta 1 , M. D’Altilio 1 , A. Curtsinger 1 , T.D. Canerdy 1 , J.T. Goad 1 , M. Bagchi 2 , D. Bagchi 2 1 Murray
USA;
State University, Hopkinsville/Murray, KY,
2 InterHealth Research Center, Benicia, CA, USA
Arthritis in large breed dogs is as common as in humans. Arthritis is closely associated with obesity. Obese arthritic dogs were treated with selected combinations of three supplements including glycosylated type-II collagen (UC-II), Glucosamine HCl (GLU), and Chondroitin sulfate (CH). Dogs were daily supplemented with either placebo (Gr-I), 10 mg UC-II (Gr-II), 2000 mg GLU + 1600 mg CH (Gr-III), or UC-II + GLU + CH (GrIV) for 120 days, followed by a 30-day withdrawal. Dogs were examined on a monthly basis for overall pain, pain upon limb manipulation, and exercise-associated lameness. Gr-I exhibited no improvement. Gr-II showed significant reductions in pain within 30–60 day of treatment. Maximum pain reductions were noted after 120 day (overall pain, 62%; pain upon limb manipulation, 91%; and exercise-associated lameness, 78%). Gr-III dogs showed some pain alleviation, while Gr-IV exhibited marked reductions (57%, 53%, and 60%, respectively). 30-Day withdrawal led to pain relapse in all dogs. Serum samples were analyzed for markers of liver function (bilirubin and ALT), renal and heart function (BUN, creatinine and CK). Body weight and temperature were measured. Serum chemistry, body weight and temperature remain unchanged. Thus, daily treatment of arthritic dogs with UC-II alone or in combination with GLU + CH significantly ameliorates the signs of arthritis, and supplements used in the present study are safe and well tolerated without any side effects. doi:10.1016/j.toxlet.2006.07.311 P26-19 Drug analyses of necrophagous insects and human tissues Marija Definis-Gojanovic, Davorka Kokan, Bogomir Milosevic
Sutlovic, Bozo
University Hospital Split, Split, Croatia Necrophagous insects may provide useful information concerning the time, place and cause of death. In addition, they can serve as reliable alternate specimens for toxicological analyses in the cases when human tissues
S311
and fluids, normally taken during autopsies, are absent due to decomposition of the corpses. This paper reports the results of drug analyses of the developmental stages of two flies species (Calliphoridae and Sarcophagidae), collected from the body of middleage man who had committed suicide approximately 3 weeks prior his corpse was found. Analyses of multiple samples (human tissues and maggots) were performed using a gas chromatography–mass spectrography, and amphetamine was detected in all samples. While the qualitative relationship of the results was without any doubt, the quantitative results were less clear and further research in this area is suggested. doi:10.1016/j.toxlet.2006.07.312 P26-20 Efficacy of different medical herbal preparations as hepatoprotective agents Mohey M. Ellithy, Somaia A. Nada Pharmacology Department, National Research Centre, P.O. 12622 Dokki, Cairo, Egypt In folk medicine, there are many herbal preparations have been used for their hepatoprotective activities. One of the most common recipes contain from equal parts (w/w) of decoction of (10% concentration): Peumus boldus (leaves), Cichorium intybus (root) and Nigella sativa (seed) (Recipe 1). Glycyrrhazia rhizome (root) was replaced with Cichorium intybus (Recipe 2) or added (Recipe 3). Three groups of normal albino rat were orally administrated 1.5 ml/100 g of Recipe 1 (group 1), Recipe 2 (group 2) or Recipe 3 (group 3) and the control group (group 4) was given 1.5 ml/100 g distilled water daily for 30 successive days. Results for normal groups revealed that Recipe 1, 2 and 3 were decreased plasma ␥glutamyl transferase (GGT): −6.1%, −26.7%, −31.5%; ALT: −3.8%, −13.2%, 17.6%; AST: −5.9%, −6.8%, −21.5%; triglycerides: 1.8%, 0%, −13%; cholesterol: −2.4%, −1.2%, −1.9% and sleeping time: 0.5%, 1.4%, 0.9%, respectively, versus control values. Second set of experiment, four groups of carbon tetrachloride-hepatic damaged rats were given the three recipes with the same above oral doses before carbon tetrachloride for 2 weeks, then followed by another 2 weeks after induction of the hepatic damage. The results indicated that significant decrease in GGT: −70%, −74.5%, −82.0%; ALT: −30.1%, −36.8%, −49.0%; AST: −9.9%, −33.3%, −43.8%; triglycerides: −11.8%, −10.5%, −17.0%; cholesterol: −17.4%, −16.4%, −24.4% and sleeping time: −24.0%, −25.1%, −37.9%, respectively, versus carbon tetrachloride-hepatic dam-
S312
Abstracts / Toxicology Letters 164S (2006) S1–S324
aged rats .In conclusion: the modified Recipe 3 was found to be more potent than Recipe 1 or 2. doi:10.1016/j.toxlet.2006.07.313 P26-21 HPLC method for methadone quantification in biological samples Anne-Marie Ciobanu, Daniela Luiza Baconi, Maria Barca, Dan Balalau, Mihaela Ilie, Ivonne Pencu University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania The use of methadone in substitution treatment of opiate addict patients is well documented. Clinical success in the methadone substitution treatment depends on the methadone suitable doses to maintain blood levels in the pharmacologically effective range. Many study highlighted the insufficient methadone dose as a major cause of the treatment failure. Several evidences exist supporting a relationship between methadone dosage and plasma methadone concentration in addicted patients during substitution therapy. We present a sensitive reversed-phase HPLC method for methadone quantification in plasma. Several HPLC columns have been tested and a RP-18, 125 cm × 0.46 cm (i.d.) packed with 5 m diameter particles has been selected. As a mobile phase, 0.1 trifluoroacetic acid–methanol (60:40, v/v), has been used. Methadone was detected at 210 nm. Linear relationships between peak area and methadone concentrations were obtained in the range of 0.0275–0.22 g/mL. The method has been validated for determination of plasma concentration of methadone. A liquid–liquid extraction procedure has been applied. The method is precise and accurate (mean recovery percent 92.34%), with a LOQ of 2.5 ng/mL. The developed method was applied to monitoring methadone plasma levels in heroin addicts patients, during methadone substitution treatment conducted at Sf. Stelian Center for Evaluation and Treatment of Addictions, Bucharest. Considerable inter-individual variations of methadone plasma concentrations have been demonstrated. doi:10.1016/j.toxlet.2006.07.314
P26-22 Toxic affects of HCG on the distribution pattern of mature rat uterine surface glycoconjugates during implantation period Aliabadi Elham, Talaii khozani Tahereh, Mesbah ardekani seyed Fakhredin, Makoolati Zohreh Department of Anatomy, Medical School, Shiraz University of Medical Science, Iran Introduction: Unovulatory period is one of the most causes of infertility .One of the treatment to such cases is hormone therapy. These hormones may have toxic affect on the molecular organization of uterine surface e.g. glycoconjugates. Glycoconjugates are one of the most important molecules of the uterine surface which play an important role in embryo implantation. In this study, the toxic effects of one of these gonadotropin hormones, Human Chorionic Gonadotropin (HCG), on glycoconjugates of uterine surface (apical membrane, Golgi zone and basement membrane of rat endometrial cells and uterine glands) during implantation period were studied. Material and method: Sixteen mature female rat was selected and divided to two groups (experimental and control groups). Experimental rats injected with 10 IU HCG intraperitoneally in estrus phase and mated with proven fertile male rats. The observation of vaginal plug was considered as 0.5 day of pregnancy. The rats were sacrificed at 5.5 day of pregnancy (time of implantation) and their uteruses were removed. Control rats become pregnant without any injection. The pregnant uterine tissues were fixed in bouin solution and embedded in wax. Lectin histochemistry was done with use of WGA, DBA, PNA, ConA, SBA and UEA lectins. Results: The intensity of the reaction to WGA in apical membrane, Golgi zone and uterine gland and the reaction of uterine gland to DBA and UEA were significantly low in experimental groups. Conclusion: HCG can induce its indirectly toxic effects on implantation rate via changes in uterine surface glycoconjugates. doi:10.1016/j.toxlet.2006.07.315