Katharine Raquel Pereira dos Santos

Teratogenic Effect of Usnic Acid from Cladonia substellata Vainio during Organogenesis

Studies about toxicological potential of usnic acid are limited. This way, the vast majority of data available in the literature are related only to biological activities. This is the first study that aimed to evaluate the oral toxicity of usnic acid during the period of organogenesis. Females rats were distributed in the control groups, treated I and II, at doses of 15 and 25 mg/kg, administered by gavage during the 6° to 15° days of pregnancy. After 20 days the fetuses were removed and analyzed. A reduction in weight gain during pregnancy, increased resorption, reduction in the number of viable fetuses, and their body weight were observed. Morphological changes in the litter were visualized as exposure of the eye and atrophy of the limbs at the dose of 25 mg/kg. Histological analysis of the liver of the fetus showed reduction in the number of megakaryocytes between experimental groups and increase in the number of hepatocytes in a dose of 25 mg/kg. The experimental model used in this study reveals teratogenic effect of usnic acid in the period of organogenesis. Since this achievement, the importance of evaluating the toxic effects of natural substances is imperative, in order to elucidate the care in their indication as drug.

Protective effect of exogenous melatonin in rats and their offspring on the genotoxic response induced by the chronic consumption of alcohol during pregnancy

Maternal alcoholism can induce serious injuries in embryonic and fetal development. The metabolism of alcohol increases the production of free radicals and acetaldehyde, molecules capable of reacting with DNA, impairing organogenesis. Melatonin is a powerful antioxidant that can act as a protective agent against DNA damage caused by genotoxic agents, such as ethanol. This study evaluated the protective effect of exogenous melatonin in rats and their offspring on the genotoxic response induced by chronic alcohol consumption during pregnancy. Twenty-five pregnant rats were divided into the following groups: NC - Negative control; ET - Rats receiving ethanol (3 g/kg/day); ET+10 M - Rats receiving ethanol (3 g/kg/day) and melatonin (10 mg/kg/day); ET+15 M - Rats receiving ethanol (3 g/kg/day) and melatonin (15 mg/kg/day); PC - Positive control (40 mg/kg cyclophosphamide). The dams and 10 pups (five males and five females) from each group were anesthetized to collect blood and liver from the dams and blood, liver and brain of neonates to evaluate the frequency of DNA damage by the comet assay. Blood was also used for the micronucleus test. The results demonstrated a significant increase in DNA damage in the blood and liver cells of dams receiving ethanol and their offspring as well as in the brain of these neonates. Treatments with melatonin (10 and 15 mg/kg/day) significantly reduced the genotoxicity caused by ethanol in the blood of dams and neonates (males and females), liver of dams and male offsprings, and in the brain of female offsprings. It was shown that only the female offspring exposed to maternal alcohol consumption showed a higher frequency of micronuclei in polychromatic erythrocytes. Consequently, exogenous melatonin may be a promising therapeutic agent against genotoxic damage induced by alcohol; however, further studies are needed to confirm these benefits.

Hepatic toxicity caused by PLGA-microspheres containing usnic acid from the lichen C ladonia substellata (AHTI) during pregnancy in Wistar rats

This study aimed to evaluate the teratogenic and hepatotoxic potential of the usnic acid encapsulated into PLGA-microspheres. In total, 12 female Wistar rats in pregnancy were randomly distributed in the control group (n= 6) that received 1.0 mL of physiological solution and treatment group (n= 6) that received 25 mg/kg of encapsulated usnic acid by oral administration. All females were euthanized at day 20 of pregnancy and their fetuses were removed and analyzed. During the pregnancy was observed a reduction in weight gain. There was no difference in serum transaminases levels analyzed as well as any difference in liver weight in both groups. The histomorphometric analysis of the liver from the treatment group revealed an increase in number of hepatocytes and a decrease in nuclear area of these cells. Moreover, no alteration was observed in cell area of hepatocytes or number of Kupffer cells. The fetuses had an increase in total number of hepatocytes and a reduction in the amount of megakaryocytes. These results show the hepatotoxic potential of usnic acid during pregnancy. However, its toxicity can be minimized by encapsulation in microspheres.

PRIMEIRO REGISTRO DE ESQUISTOSSOMOSE DA PRÓSTATA EM PERNAMBUCO, BRASIL: A EXPRESSÃO DA CRONICIDADE DE UMA ENDEMIA

Schistosomiasis has affected the rural population of Pernambuco, Brazil, for centuries. The hepatosplenic and neurological manifestations of this parasitosis have often been described. However, prostatic schistosomiasis caused by Schistosoma mansoni had never been registered in Pernambuco, thus the importance of this particular case being reported. Case presentation: This report records the first case of prostatic schistosomiasis in Pernambuco. A 51-year-old patient underwent partial prostatectomy due to possible cancer and was diagnosed with this ectopic form of schistosomiasis. After the surgical procedure, stool samples were collected to run Kato-Katz parasitological tests, which were positive for S. mansoni, thus confirming that the patient was still infected. Laboratory blood tests and clinical examination showed alterations in liver function and confirmed the presence of hepatointestinal damage. Patient monitoring evidenced that the prostate-specific antigen levels remained high and, one year after the first surgical intervention, a new prostatic puncture showed that schistosomiasis and fibromatosis lesions remained present. It is noteworthy that after triple praziquantel treatment (April 2014, July 2014, February 2015) parasitological stool examinations were all negative for S. mansoni. In conclusion this accidental diagnosis of prostatic schistosomiasis raises doubts regarding the ability of healthcare services to identify and treat ectopic schistosomiasis. The persistently high levels of PSA even after surgical and pharmacological treatment, indicate irreversible damage to tissue caused by S. mansoni. Therefore, healthcare services need to be prepared to investigate and diagnose these cases, with a view to preventing chronic sequelae through early treatment.

Análise histomorfométrica dos cardiomiócitos e deposição de colágeno no músculo cardíaco de ratas ooforectomizadas

This study aimed to evaluate the effect of oophorectomy on the morphometric variables of cardiomyocytes and quantification collagen in Wistar rats. Twenty rats were used and divided into two groups: GI - ovariectomized and GII - sham-ovariectomized. After recovery from anesthesia the animals were housed in separate cages and under the conditions of light / dark cycle 12/12h for a period of six months. After the experimental period, the animals were anesthetized, the heart removed and immersed in 10% formaldehyde. The fragments of the ventricles were subjected to histological analysis and stained with hematoxylin and eosin. Histomorphometric analysis (cell area and nuclear area and volume) were performed by light microscopy and ImageJ software version 1.44. The data were submitted to ANOVA and when significant, complemented by Students t test (p<0.001). There was a significant decrease in cellular and nuclear areas of the GI cardiomyocytes compared to GII and the area occupied by collagen was greater in cardiac muscle GI, when compared to GII. Therefore, it is concluded that the changes observed in the GI group cardiomyocytes, suggest a higher apoptotic activity in this group, due to decreased serum estrogen levels caused by ovariectomy and increased area occupied by collagen in oophorectomized group is associated the cardioprotective effect of estrogen.