Exposição crônica ao cloridrato de metformina e à glibenclamida causa alterações comportamentais, glicêmicas e de mortalidade em Hemigrammus caudovittatus e Danio rerio / Chronic exposure to metformin chloridrate and glibenclamide causes behavioral, blood glucose and mortality changes of Hemigrammus caudovittatus and Danio rerio

Hemigrammus caudovittatus e Danio rerio foram expostos aos hipoglicemiantes orais (HOs) cloridrato de metformina a 40µg/L e 120µg/L e glibenclamida a 0,13µg/L e 0,39µg/L durante 100 dias. Foram avaliados os efeitos tóxicos dos fármacos em relação ao peso, ao comportamento animal, à glicemia e à mortalidade. H. caudovittatus expostos à menor concentração dos fármacos apresentaram aumento significativo (P<0,05) no evento Respiração Aérea. Ainda, foi observado aumento no comportamento Descansar quando os animais foram expostos à glibenclamida a 0,39µg/L. Em D. rerio expostos ao cloridrato de metformina a 120µg/L, foi observado aumento (P<0,05) no comportamento Descansar. A glibenclamida provocou redução (P<0,05) na glicemia de H. caudovittatus. Ambos os fármacos causaram efeito letal na espécie D. rerio, contudo a glibenclamida foi mais tóxica, causando 100% de mortalidade em 30 dias de exposição. Os animais que vieram a óbito apresentaram congestão nos arcos branquiais e hemorragia. Os HOs foram desenvolvidos para apresentarem efeitos fisiológicos em mamíferos, entretanto efeitos tóxicos foram encontrados nas duas espécies de peixe estudadas. Isso levanta a preocupação sobre possíveis efeitos tóxicos de HOs e sobre quais métodos serão utilizados para a sua degradação no ambiente aquático.(AU)

Hemigrammus caudovittatus and Danio rerio were exposed to oral hypoglycemic drugs (HOs) metformin hydrochloride at 40µg/L and 120µg/L and to glibenclamide at 0.13µg/L and 0.39µg/L during 100 days. Toxic effects of the drugs were evaluated based on weight, animal behavior, blood glucose and mortality. H. caudovittatus exposed to lowest concentration of the drugs showed significant increase (P< 0.05) in the Air breathing event. Furthermore, increase in Rest event was observed when animals were exposed to glibenclamide at 0.39µg/L. An increase (P< 0.05) in the frequency of Rest behavior in the D. rerio exposed to metformin hydrochloride at 120µg/L was observed. Glibenclamide caused decrease (P< 0.05) in the blood glucose of H. caudovittatus. Both drugs caused lethal effect against D. rerio. Nevertheless, glibenclamide was more toxic causing 100% of mortality after 30 days of exposure. The animals that died showed congestion on the branchial arches and hemorrhage. The HOs were developed to have physiological effects in mammals. However, toxic effects were found in both species of fish studied. This raises concerns about possible toxic effects of HOs and what methods will be used for their degradation in the aquatic environment.(AU)

Exposição crônica ao cloridrato de metformina e à glibenclamida causa alterações comportamentais, glicêmicas e de mortalidade em Hemigrammus caudovittatus e Danio rerio / Chronic exposure to metformin chloridrate and glibenclamide causes behavioral, blood glucose and mortality changes of Hemigrammus caudovittatus and Danio rerio

Hemigrammus caudovittatus e Danio rerio foram expostos aos hipoglicemiantes orais (HOs) cloridrato de metformina a 40µg/L e 120µg/L e glibenclamida a 0,13µg/L e 0,39µg/L durante 100 dias. Foram avaliados os efeitos tóxicos dos fármacos em relação ao peso, ao comportamento animal, à glicemia e à mortalidade. H. caudovittatus expostos à menor concentração dos fármacos apresentaram aumento significativo (P<0,05) no evento Respiração Aérea. Ainda, foi observado aumento no comportamento Descansar quando os animais foram expostos à glibenclamida a 0,39µg/L. Em D. rerio expostos ao cloridrato de metformina a 120µg/L, foi observado aumento (P<0,05) no comportamento Descansar. A glibenclamida provocou redução (P<0,05) na glicemia de H. caudovittatus. Ambos os fármacos causaram efeito letal na espécie D. rerio, contudo a glibenclamida foi mais tóxica, causando 100% de mortalidade em 30 dias de exposição. Os animais que vieram a óbito apresentaram congestão nos arcos branquiais e hemorragia. Os HOs foram desenvolvidos para apresentarem efeitos fisiológicos em mamíferos, entretanto efeitos tóxicos foram encontrados nas duas espécies de peixe estudadas. Isso levanta a preocupação sobre possíveis efeitos tóxicos de HOs e sobre quais métodos serão utilizados para a sua degradação no ambiente aquático.(AU)

Hemigrammus caudovittatus and Danio rerio were exposed to oral hypoglycemic drugs (HOs) metformin hydrochloride at 40µg/L and 120µg/L and to glibenclamide at 0.13µg/L and 0.39µg/L during 100 days. Toxic effects of the drugs were evaluated based on weight, animal behavior, blood glucose and mortality. H. caudovittatus exposed to lowest concentration of the drugs showed significant increase (P< 0.05) in the Air breathing event. Furthermore, increase in Rest event was observed when animals were exposed to glibenclamide at 0.39µg/L. An increase (P< 0.05) in the frequency of Rest behavior in the D. rerio exposed to metformin hydrochloride at 120µg/L was observed. Glibenclamide caused decrease (P< 0.05) in the blood glucose of H. caudovittatus. Both drugs caused lethal effect against D. rerio. Nevertheless, glibenclamide was more toxic causing 100% of mortality after 30 days of exposure. The animals that died showed congestion on the branchial arches and hemorrhage. The HOs were developed to have physiological effects in mammals. However, toxic effects were found in both species of fish studied. This raises concerns about possible toxic effects of HOs and what methods will be used for their degradation in the aquatic environment.(AU)

Serum concentrations and renal expressions of IL-1 and TNF-a early after hemorrhage in rats under the effect of glibenclamide

PURPOSE:To investigate changes in the serum concentration and renal expression of IL-1 and TNF-α cytokines in rats that received sevoflurane and glibenclamide prior to hemorrhage.METHODS:Two groups of sevoflurane-anesthetized Wistar rats (n=10): G1 (control) and G2 (glibenclamide, 1 µg/g i.v.); hemorrhage of 30% blood volume (10% every 10 min), with replacement using Ringer solution, 5 ml/kg/h. Serum concentrations of IL-1 and TNF-α were studied in the first hemorrhage (T1) and 50 min later (T2), renal expression, at T2.RESULTS:In serum, G1 TNF-α (pg/mL) was T1=178.6±33.5, T2=509.2±118.8 (p<0.05); IL-1 (pg/mL) was T1=148.8±31.3, T2=322.6±115.4 (p<0.05); in G2, TNF-α was T1=486.2±83.6, T2=261.8±79.5 (p<0.05); IL-1 was T1=347.0±72.0, T2= 327.3±90.9 (p>0.05). The expression of TNF-α and IL-1 in the glomerular and tubular cells was significantly higher in the G2 group.CONCLUSIONS:Hemorrhage and glibenclamide elevated TNF-α and IL-1 concentrations in serum and kidneys. High levels of TNF-α already present before the hemorrhage in the glibenclamide group may have attenuated the damages found in the kidneys after the ischemia event.(AU)

Antidiabetic effect of Gymnema sylvestre in Streptozotocin induced diabetes in rats

The purpose of the study was to study the hypoglycemic effect of Gymnema sylvestre in streptozotocin induced diabetic rat model. G. sylvestre was administered at the dose rate of 50 and 100 mg/kg b w and was compared with standard hypoglycemic drug, glibenclamide for its anti hyperglycemic effect. There was improvement in various parameters such as body weight, haemoglobin, serum glucose, cholesterol, triglycerides, AST, ALT and antioxidant enzymes in all the treatment groups. G. sylvestre elicited dose dependent effect with 100 mg/kg b w being more effective in alleviating most of the diabetic clinical signs. The findings were clearly substantiated by histopathology and immunohistochemistry. In conclusion, G. sylvestre has significant antidiabetic effect at 100 mg/kg b w when administered daily for 45 days.

Antidiabetic effect of Gymnema sylvestre in Streptozotocin induced diabetes in rats

The purpose of the study was to study the hypoglycemic effect of Gymnema sylvestre in streptozotocin induced diabetic rat model. G. sylvestre was administered at the dose rate of 50 and 100 mg/kg b w and was compared with standard hypoglycemic drug, glibenclamide for its anti hyperglycemic effect. There was improvement in various parameters such as body weight, haemoglobin, serum glucose, cholesterol, triglycerides, AST, ALT and antioxidant enzymes in all the treatment groups. G. sylvestre elicited dose dependent effect with 100 mg/kg b w being more effective in alleviating most of the diabetic clinical signs. The findings were clearly substantiated by histopathology and immunohistochemistry. In conclusion, G. sylvestre has significant antidiabetic effect at 100 mg/kg b w when administered daily for 45 days.(AU)