Rutin restores adenosine deaminase activity in serum and the liver and improves biochemical parameters in streptozotocin-induced diabetic rats / Rutina restaura a atividade da Adenosina desaminase no soro e no fígado e melhora os parâmetros bioquímicos em ratos diabéticos induzidos por estreptozotocina

ABSTRACT denosine deaminase (ADA) is a critical control point in the regulation of adenosine levels. This study aimed to investigate the effects of a polyphenolic flavonoid, rutin, on the activity of ADA in serum, the cerebral cortex, liver, kidney, and biochemical parameters in diabetic rats. The animals were divided into four groups (n=6) for the following treatments: control; diabetic (streptozotocin 55 mg/kg); diabetic with rutin (100 mg/kg/day); diabetic with glibenclamide (10 mg/kg/day). After 30 days, ADA activity and biochemical parameters were analyzed. The ADA activity in the serum was significantly elevated in the diabetic group compared to the control group (p<0.01). The treatment with rutin prevented the increase in ADA activity in the STZ-induced rats when compared to control group. Our data showed that rutin reduced glucose, LDL levels, and hepatic enzymes in comparison with the control group. These results demonstrate that the increase of ADA activity observed in diabetic rats may be an important indicator of the immunopathogenesis of hyperglycemic disorders and suggest that rutin is important for regulating the enzymatic activities associated with immune, hyperglycemic, and inflammatory response in diabetes mellitus.

RESUMO A Adenosina desaminase (ADA) representa um ponto de controle crítico na regulação dos níveis de adenosina. A rutina, um flavonóide polifenólico presente em muitas plantas, foi testado para verificar a sua influência na atividade da ADA no soro, córtex cerebral, fígado rim e parâmetros bioquímicos em ratos diabéticos. Os animais foram divididos em quatro grupos cada grupo com 6 animais), tal como: controle; diabética (estreptozotocina 55 mg/kg); diabética + rutina (100 mg/kg/dia); diabético + glibenclamida (10 mg/kg/dia). Após 30 dias foram analisadas a atividade da ADA sérica e tecidual e parâmetros bioquímicos. A atividade de ADA no soro foi significativamente elevada no grupo diabético quando comparado ao grupo controle (p<0,01). O tratamento com Rutina preveniu o aumento na atividade da ADA nos ratos diabéticos, quando comparado com o grupo controle. Os resultados mostraram que a rutina reduziu a glicose, os níveis de LDL e as enzimas hepáticas, em comparação com o grupo controle. Estes resultados mostram que o aumento da atividade da ADA observado em ratos diabéticos pode ser um indicador importante da imuno-patogênese de perturbações hiperglicêmicas e sugerem que a Rutina é importante na regulação das atividades enzimáticas associadas com a resposta imunitária, hiperglicêmica e inflamatória no Diabetes mellitus.

Protective effects of Syzygium cumini seed extract against methylmercury-induced sistemic toxicity in neonatal rats.

Syzygium cumini (L.) Skeels (Sc) belongs to the medicinal plants with an important source of phenolic compounds. Sc has been shown to possess antioxidant and anti-inflammatory properties. Methylmercury (MeHg), a highly toxic environmental pollutant, induces oxidative stress and dysfunction in many cell types. This study was aimed to evaluate the effect of aqueous seed extract of Sc (ASc) on MeHg-induced toxicity in rats. Two-day-old rats (P2) received a single dose of MeHg (10 mg/kg) and two doses of ASc (0.9 mg/kg) per os. After two days, the effects of the treatment were investigated in the cerebral cortex, hippocampus, kidney, liver and urine samples. Our results demonstrated that N-acetyl-ß-D: -glucosaminidase (NAG) activity in the kidney and urine, the lipid peroxidation levels in the liver and kidney samples, as well as the adenosine deaminase (ADA) activity in the hippocampus, kidney and liver were higher in MeHg-group when compared to the control group. The administration of ASc reverted the toxic effects of MeHg. It is noteworthy to observe that the main compounds present in the ASc, as gallic acid (the major component), chlorogenic acid and rutin, might be the responsible for such benefit, since they were found to display antioxidant properties.

Allium sativum L. extract prevents methyl mercury-induced cytotoxicity in peripheral blood leukocytes (LS).

Adenosine deaminase (ADA) is involved in purine metabolism and plays a significant role in the immune system. The focus of this investigation was to examine the effects of low concentrations of organic mercury on ADA activity in human leukocytes and to investigate the relationship between these effects and cell death. We have examined the protective potential effects of Allium sativum extract (GaE) against Methylmercury (MeHg)-induced cytotoxic effects on human leucocytes under in vitro conditions. MeHg (0.05-10 microM) significantly decreased leukocyte viability (58.97% for MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) and 51.67% for Alamar Blue (AB) and this decrease was positively correlated to the MeHg-induced inhibition of ADA activity. N-acetylcysteine (NAC) and GaE prevented both the MeHg-induced cytotoxic effects on leukocytes according to MTT and AB assays and the effects on the ADA activity. The present results suggest that the protective effects of GaE against MeHg-induced leukocyte damage is related to the removal of oxidant species generated in the presence of MeHg due to the antioxidant efficacy of garlic constituents. It is important to point out that the intense presence of ADA in Leukocyte suspension (LS) highlights the relevant effects in the immune system and in vitro cytotoxicity of MeHg exposure.

Decrease of adenosine deaminase activity and increase of the lipid peroxidation after acute methotrexate treatment in young rats: protective effects of grape seed extract.

The methotrexate (MTX) is an anti-folate used to treat cancer and some inflammatory diseases. The efficacy of MTX is often limited by its severe toxicity. The present study was undertaken to determine whether Grape seed (Cabernet Sauvignon) extract (GSE) could ameliorate the MTX-induced oxidative injury and the effect on adenosine deaminase activity (ADA) in rats. The rats were pretreated with 50 mg/kg of GSE, i.p., prior to MTX administration (10 mg/kg, i.p.) with a second dose given 4 h and a third dose 16 h after MTX administration. Biochemical parameters were investigated 48 h after the last MTX administration. The administration of MTX increased thiobarbituric acid reactive species (TBARS) levels in hippocampus, kidney and liver, whereas induced a significant decreased in the ADA activity in the cerebral cortex, kidney and liver tissues. MTX administration significantly increased the activity of ALT(alanine aminotransferase) and urea levels and decreased uric acid levels in the serum. Urinary uric acid levels decreased in the MTX group when compared to those of the control group. The GSE along with MTX-administration significantly reversed these parameters toward to near normal. These results indicated that GSE could reduce hepatic and nephritic damage induced by MTX-treatment in young rats therefore having free radical scavenging.

Syzygium cumini inhibits adenosine deaminase activity and reduces glucose levels in hyperglycemic patients.

Syzigium cumini (L.) Skeels from the Myrtaceae family is among the most common medicinal plants used to treat diabetes in Brazil. Leaves, fruits, and barks of S. cumini have been used for their hypoglycemic activity. Adenosine deaminase (ADA) is an important enzyme that plays a relevant role in purine and DNA metabolism, immune responses, and peptidase activity. ADA is suggested to be an important enzyme for modulating the bioactivity of insulin, but its clinical significance in diabetes mellitus (DM) has not yet been proven. In this study, we examined the effect of aqueous leaf extracts of S. cumini (L.) (ASC) on ADA activity of hyperglycemic subjects and the activity of total ADA, and its isoenzymes in serum and erythrocytes. The present study indicates that: (i) the ADA activity in hyperglycemic serum was higher than normoglycemic serum and ADA activity was higher when the blood glucose level was more elevated; (ii) ASC (60-1000 microg/mL) in vitro caused a concentration-dependent inhibition of total ADA activity and a decrease in the blood glucose level in serum; (iii) ADA1 and 2 were reduced both in erythrocytes and in hyperglycemic serum. These results suggest that the decrease of ADA activity provoked by ASC may contribute to control adenosine levels and the antioxidant defense system of red cells and could be related to the complex ADA/DPP-IV-CD26 and the properties of dipeptidyl peptidase IV (DPP-IV) inhibitors which serve as important regulators of blood glucose.