RESUMEN
Physical exercise is the cornerstone of cardiovascular disease treatment. The present study investigated whether exercise training affects atherosclerotic plaque composition through the modification of inflammatory-related pathways in apolipoprotein E knockout (apoE(-/-)) mice with diabetic atherosclerosis. Forty-five male apoE(-/-) mice were randomized into three equivalent (n=15) groups: control (CO), sedentary (SED), and exercise (EX). Diabetes was induced by streptozotocin administration. High-fat diet was administered to all groups for 12 weeks. Afterwards, CO mice were euthanatized, while the sedentary and exercise groups continued high-fat diet for 6 additional weeks. Exercising mice followed an exercise program on motorized-treadmill (5 times/week, 60 min/session). Then, blood samples and atherosclerotic plaques in the aortic root were examined. A considerable (P<0.001) regression of the atherosclerotic lesions was observed in the exercise group (180.339 ± 75.613 x10(3)µm(2)) compared to the control (325.485 ± 72.302 x10(3)µm(2)) and sedentary (340.188 ± 159.108 x 10(3)µm(2)) groups. We found decreased macrophages, matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-8 and interleukin-6 (IL-6) concentrations (P<0.05) in the atherosclerotic plaques of the exercise group. Compared to both control and sedentary groups, exercise training significantly increased collagen (P<0.05), elastin (P<0.001), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) (P<0.001) content in the atherosclerotic plaques. Those effects paralleled with increased fibrous cap thickness and less internal elastic lamina ruptures after exercise training (P<0.05), while body-weight and lipid parameters did not significantly change. Plasma MMP-2 and MMP-3 concentrations in atherosclerotic tissues followed a similar trend. From our study we can conclude that exercise training reduces and stabilizes atherosclerotic lesions in apoE-/- mice with diabetic atherosclerosis. A favorable modification of the inflammatory regulators seems to explain those beneficial effects.
Asunto(s)
Apolipoproteínas E , Diabetes Mellitus Experimental , Interleucina-6/sangre , Metaloproteinasas de la Matriz/sangre , Condicionamiento Físico Animal , Placa Aterosclerótica , Inhibidor Tisular de Metaloproteinasa-2/sangre , Animales , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/terapia , Grasas de la Dieta/efectos adversos , Grasas de la Dieta/farmacología , Inflamación/sangre , Inflamación/genética , Inflamación/patología , Inflamación/terapia , Masculino , Ratones , Ratones Noqueados , Placa Aterosclerótica/sangre , Placa Aterosclerótica/etiología , Placa Aterosclerótica/genética , Placa Aterosclerótica/patología , Placa Aterosclerótica/terapia , Factores de TiempoRESUMEN
Background: Paraquat is a herbicide; commonly used by farmers in agriculture to prevent weed infestation. The non-target organic toxicity effect of this chemical motivated this study.Methods: Utilizing male albino rats of 0.2 kg average body weight; the LD100(lethal dose that gave 100death) for Paraquat was obtained as 1g/kg body weight Furthermore LD50 (median lethal dose of paraquat; ip) was obtained as 0.45 g/kg body weight using arithmetic method of karber. Six dose levels of paraquat 0; 0.09; 0.18; 0.35; 0.70; 1.00 g/kg body weight were administered intraperitoneally into the various groups of the male rats. Within 24hrs; histopathological examination in the stomach; in the small intestine and testis of the rats were performed.Results: Histopathological examination of the organs studied revealed that the stomach had mild mucosal ulceration; muscular coat atrophy; stromal oedema and tubular hyalinization which were dose- dependent. The small intestine showed mucosal ulceration; loss of villi; luminal and stromal oedema and glandular necrosis which were also dose dependent. Furthermore; the testis had classical central fibrosis; cellular polarization; tubular disorganization; necrosis and lack of mitotic figures (no cell division); oligospermia; azoospermia and hyperchromasia which were dose dependent.Conclusion: Paraquat; a notable herbicide used in agricultural weed control; had deleterious effects on such organs as stomach; small intestine and testes. Need therefore arises for caution in the handling of these chemicals as the danger of impairment of the gastrointestinal tract and indeed the reproductive system in males is a possibility