ABSTRACT
Pequi (Caryocar brasiliense Camb.), a fruit from Brazil's central region, was evaluated for its chemopreventive effects on preneoplastic liver lesions induced by the carcinogen diethylnitrosamine (DEN) in mice. BALB/c mice, 14 days of age, received an intraperitoneal injection at 10 µg/g of DEN. The mice received either of two doses of pequi oil (100 or 400 mg/kg) daily from the age of 30 days and were killed at the age of 189 days. Stereological parameters, including the volume density (Vv) and the total volume (Vtot) of the lesions (preneoplastic and adenomas), were measured and the expression of cytokeratins CK8/18 was evaluated. The total volume of lesions and adenomas was reduced by 51% in the group treated with the carcinogen and 400 mg/kg of pequi oil administered daily by an oral gavage for 25 consecutive weeks. In addition, some mice in this group did not develop lesions. Among the remaining preneoplastic lesions in this group, the number of remodelled profiles increased by 2.4-fold in the 400-mg pequi oil-treated mice relative to the 100-mg-treated mice. Our results show that pequi oil exerts a hepatoprotective effect against DEN-induced development of preneoplastic lesions and adenoma in mice and the potential for its use in the prevention of liver cancer.
Subject(s)
Diethylnitrosamine/toxicity , Disease Models, Animal , Ericales/chemistry , Liver Neoplasms, Experimental/prevention & control , Phytotherapy , Plant Oils/pharmacology , Precancerous Conditions/prevention & control , Animals , Carcinogens/toxicity , Liver Neoplasms, Experimental/chemically induced , Liver Neoplasms, Experimental/pathology , Mice , Mice, Inbred BALB C , Precancerous Conditions/chemically induced , Precancerous Conditions/pathologyABSTRACT
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive dysfunction and death of motor neurons by mechanisms that remain unclear. Evidence indicates that oxidative mechanisms contribute to ALS pathology, but classical antioxidants have not performed well in clinical trials. Cyclic nitroxides are an alternative worth exploring because they are multifunctional antioxidants that display low toxicity in vivo. Here, we examine the effects of the cyclic nitroxide tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl) on ALS onset and progression in transgenic female rats over-expressing the mutant hSOD1(G93A) . Starting at 7 weeks of age, a high dose of tempol (155 mg/day/rat) in the rat´s drinking water had marginal effects on the disease onset but decelerated disease progression and extended survival by 9 days. In addition, tempol protected spinal cord tissues as monitored by the number of neuronal cells, and the reducing capability and levels of carbonylated proteins and non-native hSOD1 forms in spinal cord homogenates. Intraperitoneal tempol (26 mg/rat, 3 times/week) extended survival by 17 days. This group of rats, however, diverted to a decelerated disease progression. Therefore, it was inconclusive whether the higher protective effect of the lower i.p. dose was due to higher tempol bioavailability, decelerated disease development or both. Collectively, the results show that tempol moderately extends the survival of ALS rats while protecting their cellular and molecular structures against damage. Thus, the results provide proof that cyclic nitroxides are alternatives worth to be further tested in animal models of ALS.
Subject(s)
Amyotrophic Lateral Sclerosis/mortality , Antioxidants/therapeutic use , Cyclic N-Oxides/therapeutic use , Motor Neurons/drug effects , Mutation/genetics , Neuroprotective Agents/therapeutic use , Superoxide Dismutase/physiology , Amyotrophic Lateral Sclerosis/drug therapy , Amyotrophic Lateral Sclerosis/pathology , Animals , Disease Models, Animal , Disease Progression , Female , Humans , Male , Motor Neurons/metabolism , Motor Neurons/pathology , Oxidative Stress/drug effects , Protein Folding , Rats , Rats, Transgenic , Spin Labels , Spinal Cord/drug effects , Spinal Cord/metabolism , Spinal Cord/pathology , Superoxide Dismutase-1 , Survival RateABSTRACT
OBJECTIVE: The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice. METHODS: Malnutrition was induced by clustering the litter size from 6-7 pups/dam (nourished control) to 12-14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40-80 microL) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin and myelin basic protein brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated. RESULTS: Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal gamma-aminobutyric acid and synaptophysin levels on day 14. CONCLUSION: We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments.