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Protective effects of fullerenol C60(OH)24 on doxorubicin-induced hepatotoxicity in rats: Pathohistological study
S146
Abstracts / Toxicology Letters 172S (2007) S1–S240
I13 Histohemical evaluation of cardioprotective effects of methylprednisolone in rats acutely poisoned by T-2 toxin
I14 Protective effects of fullerenol C60 (OH)24 on doxorubicin-induced hepatotoxicity in rats: Pathohistological study
Vesna Jacevic 1 , Aleksandra Bocarov-Stancic 2 , Radmila Resanovic 3 , Snezana Djordjevic 1 , Dubravko Bokonjic 1 , Milos Stojiljkovic 4
Vesna Jacevic 1 , Vukosava Djordjevic-Milic 2 , Viktorija Dragojevic-Simic 3 , Natasa Radic 2 , Biljana Govedarica 2 , Silva Dobric 4 , Branislava Srdjenovic 2 , Rade Injac 5 , Aleksandar Djordjevic 6 , Velibor Vasovic 2
1 National
Poison Control Centre, Military Medical Academy, Belgrade, Serbia; 2 Holding Company Centr for Bio-Ecology, Zrenjanin, Serbia; 3 Institute for Poultry Diseases, Faculty of Veterinary Medicine, Belgrade, Serbia; 4 Actavis Trading Ltd., Representative Office, Belgrade, Serbia T-2 toxin (T2) produced the signs of a shock-like syndrome characterized by massive haemorrhages, cardiomyopathy and death. The most important mechanism of its acute cardiotoxicity is intensive synthesis of pro-inflammatory mediators by mast cells. Methylprednisolone, a powerful antiinflammatory drug, suppresses the migration and activation of mast cells and synthesis of their pro-inflammatory mediators. The aim of the study was to evaluate protective effects of methylprednisolone, Lemod-solu® (LS) or/and Lemod-depo® (LD), on acute T2-induced cardiotoxicity in rats. Wistar rats were divided into fifth groups, each of them consisting of 10 animals. Their treatments were: I—control group (saline), II—T2 (1 LD50 0.23 mg/kg s.c.), III—T2 and LS (40 mg/kg i.m.), IV—T2 and LD (40 mg/kg i.m.) and V—T2, LS (40 mg/kg i.m.) and LD (40 mg/kg i.m.). Animals were sacrificed on the day 1, 3, 5, 7, 14, 21, 28 and 60 after treatment and hearts samples were evaluated using haematoxylin and eosin (HE), periodic acid-Schiff’s (PAS), Masson-Trichrom’s (MT) and Giemsa (GIM) methods. Heart damage score (HDS) was based on an estimation scale from 0 (no damage) to 5 (strong damage). LS and LD significantly decreased degree of structural lesions, irregular distribution of glycogen granules, intensity of haemorrhages, total number of mast cells and their degranulation in comparation with animals treated only with T2 (p < 0.001). Our results indicate that methylprednisolone exerts a significant protective effects against T-2 toxin-induced cardiotoxicity in rats, which is probably the result of complex inflammatory mechanisms. doi:10.1016/j.toxlet.2007.05.377
1 National
Poison Control Centre, Military Medical Academy, Belgrade, Serbia; 2 Medical Faculty, Novi Sad, Serbia; 3 Centre for Clinical Pharmacology, Military Medical Academy, Belgrade, Serbia; 4 Institute for Scientific Informations, Military Medical Academy, Belgrade, Serbia; 5 Faculty of Pharmacy, Ljubljana, Slovenia; 6 Department of Chemistry, Faculty of Science, Novi Sad, Serbia Doxorubicin (DOX), commonly used antineoplastic agent, damages bone marrow, intestinal tract and heart, but it also has some hepatotoxic effects in experimental animals. Main mechanism of its toxicity is production of free reactive oxygen species. Polyhidroxilated C60 fullerene derivatives, fullerenols, act as free radical scavengers in in vitro systems. The aim of the study was to investigate potential protective role of fullerenol C60 (OH)24 (Full) on DOX-induced hepatotoxicity in rats. Experiments were performed on adult male Wistar rats. Animals were divided into six groups, each containing eight individuals: Group I—without treatment (saline), Group II—DOX 8 mg/kg i.v., Group III—Full 50 mg/kg i.p. 30 min before DOX, Group IV—Full 100 mg/kg 30 min before DOX, Group V—Full 200 mg/kg 30 min before DOX, Group VI—Full 100 mg/kg, only. Rats were sacrificed under urethane anaesthesia on the Day 7 after treatment and livers were obtained for histopathological analysis (HE). Hepatic damage score (HDS) was based on an estimation scale from 0 (no damage) to 5 (strong damage, massive necrotic fields). A mean value of HDS in DOX-treated rats was significantly increased comparing to control animals. Pretreatment with Full in dose of 50 mg/kg significantly reduced HDS compared with animals treated with DOX only, what was not the case with other 2 doses of Full. According to our results, Full exerted protective effects on rat liver by ameliorating cytotoxic effects on hepatocytes, as well as dilatation of liver blood vessels caused by DOX itself. doi:10.1016/j.toxlet.2007.05.378
Abstracts / Toxicology Letters 172S (2007) S1–S240
I13 Histohemical evaluation of cardioprotective effects of methylprednisolone in rats acutely poisoned by T-2 toxin
I14 Protective effects of fullerenol C60 (OH)24 on doxorubicin-induced hepatotoxicity in rats: Pathohistological study
Vesna Jacevic 1 , Aleksandra Bocarov-Stancic 2 , Radmila Resanovic 3 , Snezana Djordjevic 1 , Dubravko Bokonjic 1 , Milos Stojiljkovic 4
Vesna Jacevic 1 , Vukosava Djordjevic-Milic 2 , Viktorija Dragojevic-Simic 3 , Natasa Radic 2 , Biljana Govedarica 2 , Silva Dobric 4 , Branislava Srdjenovic 2 , Rade Injac 5 , Aleksandar Djordjevic 6 , Velibor Vasovic 2
1 National
Poison Control Centre, Military Medical Academy, Belgrade, Serbia; 2 Holding Company Centr for Bio-Ecology, Zrenjanin, Serbia; 3 Institute for Poultry Diseases, Faculty of Veterinary Medicine, Belgrade, Serbia; 4 Actavis Trading Ltd., Representative Office, Belgrade, Serbia T-2 toxin (T2) produced the signs of a shock-like syndrome characterized by massive haemorrhages, cardiomyopathy and death. The most important mechanism of its acute cardiotoxicity is intensive synthesis of pro-inflammatory mediators by mast cells. Methylprednisolone, a powerful antiinflammatory drug, suppresses the migration and activation of mast cells and synthesis of their pro-inflammatory mediators. The aim of the study was to evaluate protective effects of methylprednisolone, Lemod-solu® (LS) or/and Lemod-depo® (LD), on acute T2-induced cardiotoxicity in rats. Wistar rats were divided into fifth groups, each of them consisting of 10 animals. Their treatments were: I—control group (saline), II—T2 (1 LD50 0.23 mg/kg s.c.), III—T2 and LS (40 mg/kg i.m.), IV—T2 and LD (40 mg/kg i.m.) and V—T2, LS (40 mg/kg i.m.) and LD (40 mg/kg i.m.). Animals were sacrificed on the day 1, 3, 5, 7, 14, 21, 28 and 60 after treatment and hearts samples were evaluated using haematoxylin and eosin (HE), periodic acid-Schiff’s (PAS), Masson-Trichrom’s (MT) and Giemsa (GIM) methods. Heart damage score (HDS) was based on an estimation scale from 0 (no damage) to 5 (strong damage). LS and LD significantly decreased degree of structural lesions, irregular distribution of glycogen granules, intensity of haemorrhages, total number of mast cells and their degranulation in comparation with animals treated only with T2 (p < 0.001). Our results indicate that methylprednisolone exerts a significant protective effects against T-2 toxin-induced cardiotoxicity in rats, which is probably the result of complex inflammatory mechanisms. doi:10.1016/j.toxlet.2007.05.377
1 National
Poison Control Centre, Military Medical Academy, Belgrade, Serbia; 2 Medical Faculty, Novi Sad, Serbia; 3 Centre for Clinical Pharmacology, Military Medical Academy, Belgrade, Serbia; 4 Institute for Scientific Informations, Military Medical Academy, Belgrade, Serbia; 5 Faculty of Pharmacy, Ljubljana, Slovenia; 6 Department of Chemistry, Faculty of Science, Novi Sad, Serbia Doxorubicin (DOX), commonly used antineoplastic agent, damages bone marrow, intestinal tract and heart, but it also has some hepatotoxic effects in experimental animals. Main mechanism of its toxicity is production of free reactive oxygen species. Polyhidroxilated C60 fullerene derivatives, fullerenols, act as free radical scavengers in in vitro systems. The aim of the study was to investigate potential protective role of fullerenol C60 (OH)24 (Full) on DOX-induced hepatotoxicity in rats. Experiments were performed on adult male Wistar rats. Animals were divided into six groups, each containing eight individuals: Group I—without treatment (saline), Group II—DOX 8 mg/kg i.v., Group III—Full 50 mg/kg i.p. 30 min before DOX, Group IV—Full 100 mg/kg 30 min before DOX, Group V—Full 200 mg/kg 30 min before DOX, Group VI—Full 100 mg/kg, only. Rats were sacrificed under urethane anaesthesia on the Day 7 after treatment and livers were obtained for histopathological analysis (HE). Hepatic damage score (HDS) was based on an estimation scale from 0 (no damage) to 5 (strong damage, massive necrotic fields). A mean value of HDS in DOX-treated rats was significantly increased comparing to control animals. Pretreatment with Full in dose of 50 mg/kg significantly reduced HDS compared with animals treated with DOX only, what was not the case with other 2 doses of Full. According to our results, Full exerted protective effects on rat liver by ameliorating cytotoxic effects on hepatocytes, as well as dilatation of liver blood vessels caused by DOX itself. doi:10.1016/j.toxlet.2007.05.378