Flavonoids Effects on Hepatocellular Carcinoma in Murine Models: A Systematic Review

The hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. It occurs primarily as manifestation of other pathological processes, such as viral hepatitis, cirrhosis, and toxin exposure that affect directly the cellular process. Studies were selected from PubMed and Scopus databases according to the PRISMA statement. The research filters were constructed using three parameters: flavonoids, hepatocellular carcinoma, and animal model. The bias analysis of the 34 selected works was done using the ARRIVE guidelines. The most widely used flavonoid in the studies was epigallocatechin gallate extracted from green tea. In general, the treatment with different flavonoids presented inhibition of tumor growth and antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory activities. The bias analysis evidenced the absence of methodological processes in all studies, such as the age or weight of the animals, the method of flavonoids’ extraction, or the experimental designs, analytical methods, and outcome measures. It has been known that flavonoids have a protective effect against HCC. However, the absence or incomplete characterization of the animal models, treatment protocols, and phytochemical and toxicity analyses impaired the internal validity of the individual studies, making it difficult to determine the effectiveness of plant-derived products in the treatment of HCC

Applicability of Isolates and Fractions of Plant Extracts in Murine Models in Type II Diabetes: A Systematic Review

Type II diabetes mellitus is one of the most common public health problems worldwide. Its increasing prevalence in several countries and the difficult metabolic control of individuals with the disease justify studying strategies for primary prevention. The population has sought alternative and cheaper ways to treat the disease, including the use of plants considered medicinal by the population. In this study, we carried out a systematic review on the applicability of isolates and fractions of plant extracts in animal models in type II diabetes. A literature search was performed in MEDLINE/PubMed and Scopus databases. Studies using other experimental animals (horses, rabbits, and monkeys) and humans as well as articles in Chinese, German, and Russian were excluded. We assessed the quality of the studies included by using the criteria described in the ARRIVE guidelines. In general, the animals that received fractions or isolates presented reduced blood glucose levels, normalization of body weight and plasma insulin levels, and reduced total triglycerides and cholesterol. In addition, we observed wide variation among the analyzed parameters, which hindered comparison between the studies found. In further studies, standardized reports and experimental design would help to establish comparable study groups and advance the overall knowledge, thus facilitating translatability from animal data to human clinical conditions

Euterpe edulis

We investigated the effects of E. edulis bioproducts (lyophilized pulp [LEE], defatted lyophilized pulp [LDEE], and oil [EO]) on nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in rats. All products were chemically analyzed. In vivo, 42 rats were equally randomized into seven groups receiving standard diet, HFD alone or combined with EO, LEE, or LDEE. After NAFLD induction, LEE, LDEE, or EO was added to the animals’ diet for 4 weeks. LEE was rich in polyunsaturated fatty acids. From LEE degreasing, LDEE presented higher levels of anthocyanins and antioxidant capacity in vitro. Dietary intake of LEE and especially LDEE, but not EO, attenuated diet-induced NAFLD, reducing inflammatory infiltrate, steatosis, and lipid peroxidation in liver tissue. Although both E. edulis bioproducts were not hepatotoxic, only LDEE presented sufficient benefits to treat NAFLD in rats, possibly by its low lipid content and high amount of phenols and anthocyanins

Influence of the gallium arsenide laser and gallium aluminum arsenide laser and healing oitment in the cutaneous wounds in Wistar rats

O presente trabalho teve como objetivo avaliar o efeito cicatrizante do laser arseneto de gálio - alumínio (GaAsAl) 830nm (30J/cm2) (60J/cm2) e do laser arseneto de gálio (GaAs) 904nm (4J/cm2), comparando com a pomada Dersani®. Os parâmetros analisados foram a quantidade de fibras colágenas tipo I e III e a área de contração da ferida nos diferentes tratamentos. Foram analisadas também as influências dos diferentes tratamentos sobre o peso e os valores hematológicos dos animais. Foram utilizados 30 ratos Wistar adultos jovens, machos, com peso médio de 324g, separados em cinco grupos, cada grupo com seis animais. Os animais do grupo 1 foram tratados com o laser GaAs (4J/cm2), os animais do grupo 2 tratados com o laser GaAsAl (30J/cm2), no grupo 3 os animais receberam radiação do laser GaAsAl (60J/cm2), no grupo 4 os animais receberam o tratamento tópico com a pomada Dersani® e no grupo 5 os animais tiveram as feridas tratadas com salina. Cada animal teve o dorso depilado e foram feitas cinco feridas padronizadas, marcando-se previamente a área e removendo-se a pele. O material para análise histológica foi corado com picrosírius, fotografados e as fotos analisadas no programa Quantum, baseado nas cores primárias (vermelho, verde, azul). Foi observada uma diferença estatística significativa do peso dos animais em relação aos diferentes tratamentos e o tempo do experimento. Considerando a área da ferida, os melhores resultados para o fechamento da ferida foram obtidos dos grupos tratados com o laser GaAs (4J/cm2) e GaAsAl (60J/cm2). A contagem global de leucócitos nos diferentes tratamentos não apresentou diferença significativa, exceto nos animais tratados com o Dersani® onde houve aumento significativo no número de monócitos. Os tratamentos com salina e o laser GaAsAl 30J/cm2 apresentaram aumento no número de neutrófilos. O maior número de fibras colágenas do tipo III foi observado nos animais irradiados com o laser GaAsAl 30J/cm2. Em relação às fibras de colágeno do tipo I, os diferentes tratamentos não apresentaram um aumento significativo. Foi observado então que o laser GaAsAl 30J/cm2 foi efetivo na produção de fibras colágenas tipo III e no processo cicatricial e que o laser GaAs (4J/cm2) foi efetivo para promover o fechamento da área da ferida.The present work had as objective evaluates the healing effect of the gallium aluminum arsenide (GaAsAl) 830nm (30J/cm2) (60J/cm2) laser and gallium arsenide (GaAs) 904nm (4J/cm2) laser, comparing with the Dersani® ointment. The analyzed parameters were the amount of type I and III collagen fibers, and the area of contraction of the wound in the different treatments. They were also analyzed the influence of the different treatments on the weight and the hematologic values of the animals. They were used 30 Wistar rats, young adults, males, with medium weight of 324g, separate in five groups, each group with six animals. The animals of the group 1 were treated with GaAs (4J/cm2) laser, the animals of the group 2 treated with the GaAsAl (30J/cm2) laser, in the group 3 the animals received radiation of the GaAsAl (60J/cm2) laser, in the group 4 the animals received the topical treatment with the Dersani® ointment and in the group 5 the animals had the wound treated with saline. Each animal had the back waxed and were made five standardized wounds, previously marking the area and removing the skin. The material for histological analyze was dyed with picrosirius, photographed and the pictures analyzed in the program Quantum, based on the primary colors (Red, Green, Blue). It was observed a significant statistical difference of the weigth of the animals in relation to the different treatments and the time of the experiment. Considering the area of the wound, the best results for the closing of the wound were obtained of the groups treated with the GaAs (4J/cm2) laser and GaAsAl (60J/cm2) laser. The leukocyte global count in the different treatment didn t present significant difference, except in the animals treated with Dersani® where there was significant increase in the number of monocytes. The treatments with saline and GaAsAl (30J/cm2) laser presented increase in the number of neutrophils. The larger number of type III collagen fibers was observed in the animals irradiated with the GaAsAl (30J/cm2) laser. In relationship to the type I collagen fibers, the different treatments didn t present a significant increase. It was observed then that the GaAsAl (30J/cm2) laser was effective in the production of type III collagen fibers and in the cicatricial process and that the GaAs (4J/cm2) laser it went effective to promote the closing of the area of the wound

Hepatoprotective activity of bark extract Bathysa cuspidata (A. St-Hil) Hook.f. against oxidative stress induced by carbon tetrachloride in Wistar rats

A Bathysa cuspidata pertencente à família Rubiaceae nativa da Mata Atlântica, é usada na medicina popular brasileira para tratamento de doenças do estômago, fígado e como cicatrizante. O objetivo do presente estudo foi investigar o efeito do extrato da casca de Bathysa cuspidata (A. St. Hil.) Hook. f. sobre lesões hepáticas induzidas em ratos Wistar pelo tetracloreto de carbono (CCl4). A lesão hepática foi induzida por meio da administração intraperitoneal de CCl4, a cada 48 horas, durante 12 dias. O tratamento dos animais com extrato de B. cuspidata (EBC) foi realizado por meio de gavagem. Setenta e sete ratos foram aleatoriamente divididos em 10 grupos, com 7 animais cada, para a realização do estudo curativo e preventivo, sendo constituídos da seguinte forma: Grupos Curativo: Grupo 1: CCl4+12 (eutanasiado 12 dias após o término de administração do CCl4); Grupo 2: CCl4 (eutanasiado 24hs após a administração da última dose de CCl4); Grupo 3: CCl4+ Dimetilsulfóxido (DMSO durante 12 dias, após a aplicação do CCl4); Grupo 4: EBC (EBC 400mg/kg durante 12 dias); Grupo 5: CCl4+EBC 200mg/kg e Grupo 6: CCl4+ EBC 400mg/kg, ambos durante 12 dias. Grupos Preventivo: Grupo 1 (G1): CCl4 sem EBC; Grupo 2 (G2): DMSO+CCl4 (dimetil sulfóxido, 700&#956;l); Grupo 3(G3): EBC (somente EBC 200mg/kg durante 18 dias); Grupo 4(G4): EBC 200mg/kg + CCl4; Grupo 5(G5): EBC 400mg/kg+CCl4. Todos os animais começaram a receber o extrato seis dias antes do início da aplicação do CCl 4. Curativo: O grupo 2 apresentou redução significativa no peso final e no índice hepatossomático em relação aos demais grupos e, em relação à alanina aminotransferase (ALT) e aspartato aminotransferase (AST), este grupo apresentou os maiores valores no soro. EBC promoveu redução na quantidade de hidroperóxidos, malondialdeído e gotículas lipídicas no fígado quando comparado aos outros grupos. As atividades de superóxido dismutase (SOD) e catalase (CAT) aumentaram nos grupos 5 e 6 quando comparado aos outros grupos (p<0,05). Preventivo: A concentração da enzima aspartato aminotransferase (AST) diminuiu (p<0,05) no soro dos animais que receberam o extrato e a atividade das enzimas antioxidantes superóxido dismutase (SOD) e catalase (CAT) foi significativamente maior (p<0,05). Extensas áreas de necrose e gotículas lipídicas foram observadas no fígado de animais dos grupos G1 e G2. Já nos animais que receberam o extrato foi observada diminuição significativa nas áreas de gotículas lipídicas e de necrose celular (p<0,05) no tecido hepático. Os resultados confirmam o efeito hepatoprotetor da casca de B. cuspidata. Os resultados de ambos os trabalhos demonstram que o extrato da casca de B. cuspidata estimula o sistema de defesa antioxidante e reduz lesões morfológicas e funcionais no fígado de ratos Wistar expostos ao CCl4.Bathysa cuspidata belongs to the Rubiaceae family and is used in popular medicine for the treatment of stomach and liver disorders and as a healing agent. The objective this study was investigate the effect of stem bark ethanolic extract of Bathysa cuspidata (A. St. Hil.) Hook. f. on liver lesions induced by carbon tetrachloride (CCI 4) in Wistar rats. Liver lesions were induced by intraperitonial administration of CCI4 every 48 hours for 12 days. The animals were treated with B. cuspidata extract (BCE) administered by gavage. Seventy rats were randomized into 10 treatment groups with 7 animals in each group, to achieve the curative and Preventive study, being made up as follows: Curative groups: Group 1: CC!4 + 12 days; Group 2: CCI4; Group 3: CCI4 + dimethyl sulfoxide; Group 4: BCE 400 mg/kg; Group 5: CCI4 + BCE 200 mg/kg; Group 6: CCI4 + BCE 400 mg/kg. Preventive groups: Group 1 (G1): CCl4 without BCE; Group 2 (G2): DMSO + CCl4 (dimethyl sulfoxide 700 &#956;l); Group 3 (G3): BCE (BCE 400 mg/kg alone for 18 days); Group 4 (G4): BCE 200 mg/kg + CCl4; Group 5 (G5): BCE 400 mg/kg + CCl4. In all the animals, treatment with the extract was initiated six days prior to the first application of CCl4. Curative: Final weight and hepatosomatic index were significantly reduced in Group 2 compared to the other groups. Animals in Group 2 also had the highest serum ALT and AST levels. BCE administration resulted in a significant reduction in the quantity of hydroperoxides and malondialdehyde compared to the other groups. The number of lipid droplets in the liver was also lower in the BCE groups. A significant increase was found in superoxide dismutase activity and catalase enzymes in groups 5 and 6 compared to the other groups. Preventive: A significant reduction (p<0.05) in serum aspartate transaminase (AST) levels and a significant increase (p<0.05) in the antioxidant enzymes super oxide dismutase (SOD) and catalase (CAT) were found in the livers of the animals that received the extract. Extensive areas of necrosis and lipid droplets were found in the livers of the animals in G1 and G2. Conversely, a significant reduction (p<0.05) was found in the areas of lipid droplets and cell necrosis in the liver tissue of the animals that received the extract. The results of both studies demonstrate that the bark extract of B. cuspidata stimulates antioxidant defense system and reduces the morphological and functional lesions in the liver of rats exposed to CCl4