José Otávio do Amaral Corrêa

Effect of thalidomide and pentoxifylline on experimental autoimmune encephalomyelitis (EAE)

BACKGROUND Autoimmune encephalomyelitis (EAE) in Lewis rats is a classical experimental model of demyelinating inflammatory disease of the central nervous system. EAE is widely accepted for study of immune-inflammatory mechanisms in the CNS related to multiple sclerosis (MS) due to similar clinical evolution. OBJECTIVES In the present study we investigated the effects of Thalidomide and pentoxifylline during EAE development in Lewis rats. METHODS EAE was induced in Lewis rats and treatment with Thalidomide or pentoxifylline was performed. Clinical evaluation was carried out daily. Histopathological analysis of the brain tissue and spinal cord was performed. Griess method was used for determination of NO serum levels. TNF-alpha and IFN-gamma serum levels were investigated using ELISA method. RESULTS Thalidomide and pentoxifylline treatment is associated with significant reduction of neuroinflammation in CNS. Serum levels of NO, IFN-gamma and TNF-alpha showed a marked reduction. Such findings were correlated with improvement of clinical symptoms, particularly in thalidomide treated rats. CONCLUSIONS Taken together the data suggested that thalidomide and pentoxifylline may be therapeutic options for the treatment of MS, however further experiments must be performed to investigate this hypothesis.

Immunomodulatory effects of licochalcone A on experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis. Herein, we have investigated the immunomodulatory effect of licochalcone A (LicoA) on NO, H2O2, tumour necrosis factor‐alpha (TNF‐α), interferon gamma (IFN‐γ) and IL‐17 production in cultured cells from EAE mice.

Body weight gain and serum leptin levels of non-overweight and overweight/obese pregnant women

Background Our objective was to evaluate changes in serum leptin levels during pregnancy in overweight/obese and non-obese women and to assess total and percent weight gain during pregnancy as possible factors that influence leptin levels. Material/Methods In a prospective study of 42 low-risk pregnant women receiving prenatal care, we assessed serum leptin levels at gestational weeks 9–12, 25–28, and 34–37. Based on their pre-pregnancy body mass indices (BMIs), the cohort was divided into: non-overweight (BMI <25 kg/m2) and overweight/obese (BMI ≥25 kg/m2) subjects. Results We found a progressive increase in maternal weight gain during pregnancy in both groups. There was also a progressive increase in leptin levels in the 2 strata; however, the increase was significantly higher in the non-overweight patient group. We found that non-overweight pregnant women had a noticeably larger total weight gain. When analyzing the percent weight gain during pregnancy compared to the pre-pregnancy weight, the non-overweight group had a significantly greater percent weight gain than the overweight/obese group. Conclusions Our results suggest that the greater increase in leptin levels in non-overweight pregnant women can be explained by the higher percent weight gain in this group compared to overweight/obese women. These findings suggest that controlling the percent weight gain may be an important preventive measure when controlling leptin levels during pregnancy and subsequent medical complications.

Protective Effects of Baccharis dracunculifolia Leaves Extract against Carbon Tetrachloride- and Acetaminophen-Induced Hepatotoxicity in Experimental Animals

In this work we investigated the in vivo protective effects of Baccharis dracunculifolia leaves extract (BdE) against carbon tetrachloride (CCl4)- and acetaminophen (APAP)-induced hepatotoxicity. Total phenolic content, total flavonoid content, antioxidant DPPH radical scavenging activity, and HPLC analysis were performed. Our results showed that pretreatment with BdE significantly reduced the damage caused by CCl4 and APAP on the serum markers of hepatic injury, AST, ALT, and ALP. Results were confirmed by histopathological analysis. Phytochemical analysis, performed by HPLC, showed that BdE was rich in p-coumaric acid derivatives, caffeoylquinic acids and flavonoids. BdE also showed DPPH antioxidant activity (EC50 of 15.75 ± 0.43 μg/mL), and high total phenolic (142.90 ± 0.77 mg GAE/g) and flavonoid (51.47 ± 0.60 mg RE/g) contents. This study indicated that B. dracunculifolia leaves extract has relevant in vivo hepatoprotective properties.

Copaiba Oil Suppresses Inflammatory Cytokines in Splenocytes of C57Bl/6 Mice Induced with Experimental Autoimmune Encephalomyelitis (EAE)

Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis. We have investigated the immunomodulatory effects of copaiba oil (100, 50 and 25 µg/mL) on NO, H2O2, TNF-α, IFN-γ and IL-17 production in cultured cells from EAE-mice. Copaiba oil (100 µg/mL) inhibited H2O2, NO, IFN-γ TNF-α and IL-17 production spontaneously or after ConA and MOG35–55 stimulation. It is suggested that copaiba oil acts on the mechanism of development of EAE by IFN-γ, IL-17 and TNF-α inhibition, modulating the immune response on both Th1 and Th17 cells.

β-Caryophyllene ameliorates the development of experimental autoimmune encephalomyelitis in C57BL/6 mice

Multiple sclerosis is the most common autoimmune inflammatory and demyelinating disease of the central nervous system. The experimental autoimmune encephalomyelitis (EAE) is an appropriate and a well-establish model for studying the pathogenesis of MS. β-caryophyllene (BCP), a natural sesquiterpene found in many plant species, is a potent anti-inflammatory compound. Herein we investigated the in vitro and in vivo immunomodulatory effects of BCP on C57BL/6 mice induced with EAE. BCP was in vitro evaluated (4, 20, and 40μM) on splenocytes obtained from EAE-induced C57BL/6 mice, and in vivo (25 or 50mg/kg/day) orally administered on EAE-mice. The clinical course, body weight, cytokines and oxygen radicals production were investigated in C57BL/6 EAE-mice. In vitro and in vivo immunological responses were evaluated by ELISA, and CNS sections were stained by hematoxylin and eosin methods The in vitro production of H2O2, NO, IFN-γ, and TNF- α was inhibited by BCP (20 and 40μM) in cultured cells from EAE-mice. BCP (25 and 50mg/kg/day) reduced clinical score and severity of EAE and inhibited H2O2, NO, TNF-α, IFN-γ and, IL-17 production. EAE-mice, orally treated with BCP (mainly at 50mg/kg/day), displayed levels of cytokines and clinical signs similar to animals with no EAE disease, demonstrating the therapeutic action of BCP on EAE animals. Histopathological and histomorphometric analysis confirmed that BCP treatment significantly reduced the numbers of inflammatory infiltrates and attenuated neurological damages in the CNS of EAE-mice.