RESUMO
Cisplatin (CP) is a platinum compound of the alkylating agent class that is used for the treatment of various types of cancer. However, CP treatments in cancer patients are accountable for nephrotoxicity, as it is a major adverse effect. Hence, this research study was proposed to investigate the nephroprotective effect of diosmin, a flavonoid glycoside of hesperidin derivatives against cisplatin-induced kidney damage. Wistar rats received a single intraperitoneal (i.p) injection of CP (7.5 mg/kg, i.p) to induce nephrotoxicity. The administration of CP significantly (p < 0.001) increased the markers of kidney function test (creatinine, blood urea nitrogen, and uric acid) and demonstrated histopathological changes in the kidney of the CP-treated nephrotoxic group. In addition, the CP-treated nephrotoxic group demonstrated a significant (p < 0.001) increase in lipid peroxidation (LPO) levels and depleted activities of reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT).However, diosmin (100 and 200 mg/kg) treatments significantly reduced the elevated levels of kidney function test parameters and restored structural changes in the kidney (p < 0.001). The administration of diosmin (100 and 200 mg/kg) significantly (p < 0.001) reduced LPO levels, increased GSH content and showed improvements in the activities of GPx, GR, SOD and CAT. The markers of inflammatory cytokines such as IL-1ß, IL-6 and TNFα significantly (p < 0.001) increased in the CP-treated nephrotoxic group, whereas diosmin (100 and 200 mg/kg) treatments significantly (p < 0.001) reduced the elevated levels of these cytokines. The findings of this research demonstrate the nephroprotective effect of diosmin against CP-induced kidney damage. Therefore, we conclude that diosmin may be used as a supplement in the management of nephrotoxicity associated with CP treatments in cancer patients.
Assuntos
Diosmina , Nefropatias , Ratos , Animais , Cisplatino/farmacologia , Interleucina-6/metabolismo , Diosmina/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Ratos Wistar , Rim , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Nefropatias/prevenção & controle , Estresse Oxidativo , Antioxidantes/farmacologia , Citocinas/metabolismo , Superóxido Dismutase/metabolismo , Glutationa Peroxidase/metabolismoRESUMO
Liver inflammation and necrosis are the foremost problems interlinked with diabetes mellitus (DM). The methanolic extract of Sargassum muticum (MESM) plays a hepatoprotective role in streptozotocin- (STZ-) induced hepatic injury. In this study, STZ exposure induced diabetes that augmented hepatic damage, which was reflected in serum enzyme markers, the cytokine network, and caspase-3 and caspase-9 levels in Group 2. Exposure to the MESM tremendously modulated the levels of hepatic enzyme markers ALP, ACP, ALT, and AST in Groups 3 and 4. The cytokine network was well regulated by suppressing the release of cytokines, and the levels of caspase-3 and caspase-9 were also reduced in Groups 3 and 4. The present study suggests that MESM treatment at 200 and 500 mg protected the liver and also minimizes the glucose level. Thus, the MESM plays a key role in rejuvenating the liver and can modulate diabetes's pathogenic effect by reducing the glucose level.
Assuntos
Citocinas/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Extratos Vegetais/uso terapêutico , Sargassum/química , Animais , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Hepatopatias/metabolismo , Masculino , Extratos Vegetais/química , Ratos , Ratos WistarRESUMO
The in vivo antioxidant properties of green tea extract (GTE) were investigated against doxorubicin (DOX) induced cardiotoxicity in rats. In this experiment, 48 Wistar albino rats (200-250 g) were divided into eight groups (n = 6). Control group received normal saline for 30 days. Cardiotoxicity was induced by DOX (20 mg/kg ip.), once on 29th day of study and were treated with GTE (100, 200 and 400 mg/kg, p.o.) for 30 days. Aspartate aminotransferase (AST), creatinine kinase (CK), lactate dehydrogenase (LDH), lipid peroxidation (LPO), cytochrome P450 (CYP), blood glutathione, tissue glutathione, enzymatic and non-enzymatic antioxidants were evaluated along with histopathological studies. DOX treated rats showed a significant increased levels of AST, CK, LDH, LPO and CYP, which were restored by oral administration of GTE at doses 100, 200 and 400 mg/kg for 30 days. Moreover, GTE administration significantly increased the activities of glutathione peroxidase (GPX), glutathione reductase (GR), glutathione s-transferase (GST), superoxide dismutase (SOD) and catalase (CAT), in heart, which were reduced by DOX treatment. In this study, we have found that oral administration of GTE prevented DOX-induced cardiotoxicity by accelerating heart antioxidant defense mechanisms and down regulating the LPO levels to the normal levels.
Assuntos
Antioxidantes/farmacologia , Camellia sinensis , Doxorrubicina , Cardiopatias/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Administração Oral , Animais , Antioxidantes/administração & dosagem , Biomarcadores/sangue , Citoproteção , Modelos Animais de Doenças , Cardiopatias/sangue , Cardiopatias/induzido quimicamente , Cardiopatias/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/administração & dosagem , Plantas Medicinais , Ratos , Ratos Wistar , Fatores de TempoRESUMO
We have investigated the effect of methanolic extract of Rhus coriaria (RC) on hyperinsulinemia, glucose intolerance and insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by single intraperitoneal injection of streptozotocin (STZ, 100 mg/kg) to 2 days old rat pups. RC (200 mg/kg and 400 mg/kg) was administered orally once a day for 5 weeks after the animals were confirmed diabetic (i.e, 90 days after STZ injection). A group of citrate control rats were also maintained which has received citrate buffer on the 2nd day of their birth. There was a significant increase in blood glucose, glycosylated hemoglobin (HbA1c) and serum insulin levels were observed in NIDDM control rats. Treatment with RC reduced the elevated levels of blood glucose, HbA1c and insulin in the NIDDM rats. An oral glucose tolerance test (OGTT) was also performed in the same groups, in which we found a significant improvement in glucose tolerance in the rats treated with RC. The insulin sensitivity was assessed for both peripheral insulin resistance and hepatic insulin resistance. RC treatment significantly improved insulin sensitivity index (K(ITT)) which was significantly decreased in NIDDM control rats. There was significant rise in homeostasis model assessment of insulin resistance (HOMA-R) in NIDDM control rats whereas RC treatment significantly prevented the rise in HOMA-R in NIDDM treated rats. Our data suggest that methanolic extract of RC significantly delayed the onset of hyperinsulinemia and glucose intolerance and improved insulin sensitivity in NIDDM rats.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hipoglicemiantes/farmacologia , Resistência à Insulina/fisiologia , Rhus/química , Animais , Glicemia , Intolerância à Glucose/tratamento farmacológico , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/análise , Hipoglicemiantes/química , Insulina/sangue , Extratos Vegetais/farmacologia , RatosRESUMO
The aim of the present study was to investigate the effects of Withania somnifera (WS) on lipid peroxidation (LPO), activities of both non-enzymatic and enzymatic antioxidants and histopathological examination of pancreas in type 2 diabetic rats. Type 2 diabetes was induced by single intraperitoneal injection of STZ (100 mg/kg) to 2 days old rat pups. Oxidative stress was measured by tissue LPO levels, reduced glutathione (GSH) contents and by enzymatic activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT). Administration of WS to type 2 diabetic rats caused a significant decrease in blood glucose and tissue LPO levels with significant increase in GSH contents when compared with the type 2 diabetic control rats. In addition, WS treated rats also showed a significant increase in the activities of antioxidant enzymes namely GPx, GR, GST, SOD and CAT when compared with type 2 diabetic control rats. Significant reduction in the number and size of pancreatic beta-cells were preserved to near normal morphology by the administration of WS in type 2 diabetic rats as evident from histopathological examination. The results obtained clearly indicate that WS has shown strong free radical scavenging activity and helped in improving the non-enzymatic and enzymatic antioxidants in type 2 diabetic rats.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Células Secretoras de Insulina/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Withania , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Glutationa/metabolismo , Células Secretoras de Insulina/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fitoterapia , Ratos , Ratos Wistar , EstreptozocinaRESUMO
Increased oxidative stress has been implicated in the pathogenesis of dopaminergic neurodegeneration leading to the development of Parkinson's disease. In this study, we investigated whether naphtha[1,2-d]thiazol-2-amine (NTA) may ameliorate haloperidol-induced catalepsy and oxidative damage in mice brain. Haloperidol-induced catalepsy was measured with the standard bar test. The extent of oxidative stress has been evaluated by measuring levels of MDA, GSH and activities of antioxidant enzymes (SOD and GSH-Px) from brain homogenate. Haloperidol treatment significantly induced the catalepsy as observed from increased descent time measured in the bar test. Pretreatment with NTA significantly reduced the catalepsy induced by haloperidol in a dose-dependent manner. The elevated level of MDA in haloperidol-treated mice was significantly decreased by NTA pretreatment. The decreased level of GSH as well as SOD and GSH-Px activities in haloperidol-treated mice were significantly increased by NTA pretreatment. NTA reduces the oxidative stress allowing recovery of detoxifying enzyme activities and controlling free radical production, suggesting a potential role of the drug as an alternative/adjuvant drug in preventing and treating the neurodegenerative diseases, such as Parkinson's disease.
Assuntos
Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Naftalenos/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/prevenção & controle , Tiazóis/farmacologia , Animais , Antioxidantes/química , Antioxidantes/uso terapêutico , Encéfalo/enzimologia , Encéfalo/patologia , Catalepsia/induzido quimicamente , Catalepsia/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Haloperidol/farmacologia , Masculino , Malondialdeído/metabolismo , Camundongos , Naftalenos/química , Naftalenos/uso terapêutico , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/patologia , Superóxido Dismutase/metabolismo , Tiazóis/química , Tiazóis/uso terapêuticoRESUMO
We investigated the effect of an aqueous extract of Withania somnifera (WS) on insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by single intraperitoneal injection of streptozotocin (100 mg/kg) to 2 days old rat pups. WS (200 and 400 mg/kg) was administered orally once a day for 5 weeks after the animals were confirmed diabetic (i.e. 75 days after streptozotocin injection). A group of citrate control rats (group I) were also maintained that has received citrate buffer on the second day of their birth. A significant increase in blood glucose, glycosylated haemoglobin (HbA(1)c) and serum insulin levels were observed in NIDDM control rats. Treatment with WS reduced the elevated levels of blood glucose, HbA(1)c and insulin in the NIDDM rats. An oral glucose tolerance test was also performed in the same groups, in which we found a significant improvement in glucose tolerance in the rats treated with WS. The insulin sensitivity was assessed for both peripheral insulin resistance and hepatic insulin resistance. WS treatment significantly improved insulin sensitivity index (K(ITT)) that was significantly decreased in NIDDM control rats. There was significant rise in homeostasis model assessment of insulin resistance (HOMA-R) in NIDDM control rats whereas WS treatment significantly prevented the rise in HOMA-R in NIDDM-treated rats. Our data suggest that aqueous extract of WS normalizes hyperglycemia in NIDDM rats by improving insulin sensitivity.