Cardioprotective effect of lipistat against doxorubicin induced myocardial toxicity in albino rats.

Preventive role of lipistat against doxorubicin induced myocardial toxicity in rats has been reported. Cardiotoxicity was produced by doxorubicin administration (15 mg/kg for 2 weeks). Lipistat (350 mg/kg, orally) was administered as pretreatment for 2 weeks and then for 2 weeks alternated with doxorubicin. The general observations, mortality, histopathology, biomarker enzymes like lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), serum lipid profiles like total cholesterol, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), antioxidant enzymes such as glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were monitored after 3 weeks of last dose. Pretreatment with the lipistat significantly protected myocardium from the toxic effects of doxorubicin by reducing the elevated level of biomarker enzymes like LDH and CPK to the normal and serum lipids such as total cholesterol, triglyceride and LDL back to normal. Lipistat increases the decreased level of GSH, SOD and CAT and decreases the increased level of malondialdehyde in cardiac tissue. The repeated administration of doxorubicin causes cardiomyopathy associated with an antioxidant deficit and increased level of lipid profiles by interfering with fatty acid metabolism. The results support the lipid lowering and antioxidant properties of lipistat, which indicate the cardioprotective property against doxorubicin induced cardiotoxicity.

Estudo piloto do papel do probucol na proteção da lesão pulmonar induzida pela administração de doxorrubicina em ratos: análise comparativa entre microscopia óptica e microscopia eletrônica / Pilot study of probucol protection on pulmonary injury induced by doxorubicin in rats: comparison analysis between optic and eletronic microscopy

Objetivo: Estudar o papel do probucol na lesão pulmonar obtida pela administração de doxorrubicina em ratos. Método: foi realizado um estudo piloto experimental, onde o probucol foi testado como protetor da injúria pulmonar obtida pela administração de doxorrubicina em ratos. Resultados: Na análise comparativa dos grupos, estudados por microscopia óptica, não houve diferença significativa de critérios previamente definidos, exceto pelo edema pleural (p < 0,05). Já na microscopia eletrônica, a agressão da doxorrubicina foi identificada através da desorganização estrutural. No grupo que recebeu probucol e doxorrubicina, não foi observada a mesma desorganização (p < 0,05). Conclusões: os resultados deste estudo piloto sugerem que o probucol exerceu um efeito protetor no tecido pulmonar agredido pela doxorrubicina e que a microscopia eletrônica é mais sensível na identificação de critérios de injúria pulmonar decorrente da exposição à doxorrubicina (AU)

Objective: To study the role of probucol in the pulmonary injury caused by doxorubicin in rats. Methods: An experimental study was carried out to verify where the probucol was protective of the pulmonary injury caused by the administration of doxorubicin in rats. Results: In the comparative analysis of the groups studied by optic microscopy, it did not have significant difference in pre-definite criterions, except for pleural edema (p < 0,05). In eletronic microscopy, the aggression of the doxorubicin was indicated through the structural disorganization. In the group that received probucol and doxorubicin was not observed the same disorganization (p < 0,05). Conclusion: The results suggest that the probucol was effective in the protection of pulmonary injury caused by doxorubicin and that the eletronic microscopy is more sensitive for pre-definite criterions of pulmonary injury (AU)

Protective Effects of N-acetylcysteine and Selenium against Doxorubicin Toxicity in Rats

To investigate the neutralizing effect of N-acetylcysteine (NAC) and selenium (Se) aganist doxorubicin (DOX) toxicity in rats, NAC (140 mg/kg, p.o.) and Se (0.5 mg/kg, p.o.) were administered for 2 days before DOX injection and then 3 times a week. Cell viability and the level of lipid peroxidation were examined in cultured-rat astrocytes. Severe morphologic changes in the kidney of DOX group; thickening of Bowmans capsule, presence of multifocal tubular casts were observed, but not in the other treated groups. Vacuoles in some hepatic cells and focal aggregation of stellate macrophages were also detected in DOX group, but not in the other treated groups. However, the severe inhibition of spermatogenesis was found in all treated groups. The cell viability of DOX (10 mg/ml) treated group and NAC (5 mM) or Se (0.001 mg/ml) combinedtreated group was 52.5+/-2.0 % , 85.3+/-4.5 % and 75.5+/-1.6 %, respectively. In MDA (malondialdehyde) assay, the level of lipid peroxidation on DOX (10 mg/ml), NAC (5 mM) and Se (0.001 mg/ml) was 0.77+/-0.06, 0.35+/-0.06 and 0.54+/-0.11 nmol/mg protein, respectively. Thus, it is known that NAC and Se have protective effects in kidney and liver but not in the testes. Morphological change was not detected in brain and heart in all groups for experiment period. From this in vitro study, it is known that NAC and Se protect well the astrocytes against DOX induced-cell damage.

Influence of alpha-tocopherol on doxorubicin-induced lipid peroxidation, swelling and thiol depletion in rat heart mitochondria.

Effect of alpha-tocopherol on doxorubicin-induced swelling in rat heart mitochondria was studied in vitro. Mitochondria was isolated from control and alpha-tocopherol treated rats. Various concentrations of doxorubicin were added to mitochondrial suspension. Swelling, lipid peroxidation and thiol depletion were measured. Concentration and time dependent increase in swelling was noted with increase in lipid peroxidation and thiol depletion in mitochondria isolated from control rats. In alpha-tocopherol treatment, thiol depletion is significantly prevented with reduced lipid peroxidation and swelling.

Effect of alpha-tocopherol on doxorubicin-induced changes in rat heart lysosomal enzymes.

Effect of doxorubicin on heart lysosomes were studied in rats with or without the administration of alpha-tocopherol. Rats were treated with doxorubicin (2.5 mg/kg body wt, iv) once a week for 8 weeks. alpha-tocopherol (400 mg/kg body wt) was co-administered orally for 2 months. Activities of acid phosphatase, beta-D-glucuronidase, cathepsin-D and beta-D-galactosidase were decreased in heart lysosomes but increased significantly in serum. A significant increase in lysosomal lipid peroxide level was noted. alpha-tocopherol co-administration reduced the lipid peroxide level as well as maintained the above mentioned enzyme activities.

Lipids and lipoprotein profile in doxorubicin treated rats: influence of alpha-tocopherol administration.

The effect of doxorubicin (DXR) on the levels of heart, liver and plasma lipids and plasma lipoproteins were studied in rats. Rats were treated with DXR (2.5 mg/kg body weight weekly for 8 weeks, iv) with or without alpha-tocopherol (alpha-TPL) (400 mg/kg body wt daily for 60 days) co-administration. DXR treated rats showed increase in plasma total cholesterol, triglycerides and phospholipids. The activities of lecithin cholesterol-acyl transferase and hepatic and extrahepatic lipoprotein lipase were lowered significantly with concomitant increase in liver and heart lipid peroxide levels in DXR treatment. HDL cholesterol level was found to be decreased significantly in DXR treated rats as a result of which there was an increase of LDLc/HDLc ratio. alpha-TPL coadministration brought back the enzyme activity to near normal and reduced the level of lipid peroxides. The lipid changes were minimum in rats treated with both alpha-TPL and DXR. This study suggests that the toxicity of DXR is reflected in lipids and lipoprotein profile.

Alpha-tocopherol reduces doxorubicin-induced toxicity in rats--histological and biochemical evidences.

The beneficial effect of alpha-tocopherol on doxorubicin-induced toxicity was studied in rats. alpha-Tocopherol (400 mg/kg/day) was administered orally, daily for a period of 2 months along with/without doxorubicin (2.5 mg/kg, i v weekly once for 8 weeks). Histology showed liver necrosis, heart myocyte degeneration, glomerular and tubular degeneration, cellular infiltration and desquammation of intestinal mucosa in doxorubicin treated animals. There was a significant increase in lipid peroxide levels measured in terms of "TBA reactants" in all these organs. These changes were associated with elevated levels of serum enzymes such as transaminases, creatine kinase and lactate dehydrogenase. The pathological observations, were minimal in animals receiving both doxorubicin and alpha-tocopherol. The lipid peroxide levels were low with concomitant normal levels of serum and intestinal enzymes in those animals.