Mohammad Shokrzadeh1,2, Atefeh Mirshafa2,3, Niusha Yekta Moghaddam2,3, Behnoosh Birjandian2,3, Fatemeh Shaki1,2. 1. a Pharmaceutical Sciences Research Center, Faculty of Pharmacy , Mazandaran University of Medical Sciences , Sari , Iran. 2. b Department of Toxicology and Pharmacology, Faculty of Pharmacy , Mazandaran University of Medical Sciences , Sari , Iran. 3. c Student Research Committee , Mazandaran University of Medical Sciences , Sari , Iran.
Abstract
INTRODUCTION: Uncontrolled chronic hyperglycemia in diabetic patients could result in various complications, including neurotoxicity. Urtica dioica L. (UD) is known for its hypoglycemic and antioxidant effects. In this study, we evaluated the efficacy of UD and pioglitazone (PIO) in reduction of neurotoxicity and oxidative stress in streptozocin-induced diabetic mice. MATERIALS AND METHODS: Male mice were divided into seven groups: control, diabetic, dimethyl sulfoxide-treated control, PIO-treated, UD-treated, UD-PIO-treated, and vitamin E-treated. For induction of diabetes, streptozocin was injected in a single dose (65 mg/kg, i.p.). All treatments were performed for 5 weeks. Neurotoxicity was evaluated through hot plate and formalin test. Then, animals were killed, brain tissue was separated and the mitochondrial fraction was isolated with different centrifuge technique. Also, oxidative stress markers (reactive oxygen species, lipid peroxidation, protein carbonyl, glutathione) were measured in brain. Mitochondrial function was evaluated by MTT test in brain isolated mitochondria. RESULTS: Elevation of oxidative stress markers and mitochondrial damage were observed in diabetic mice compared to control group. Administration of PIO and UD ameliorated the oxidative stress and mitochondrial damage (p < 0.05) in diabetic mice. Also increase in pain score was shown in diabetic mice that treatment with UD and PIO diminished elevation of pain score in diabetic mice. Interestingly, simultaneous administration of PIO and UD showed synergism effect in attenuation of oxidative stress and hyperglycemia. CONCLUSION: UD showed a therapeutic potential for the attenuation of oxidative stress and diabetes-induced hyperglycemia that can be considered as co-treatment in treatment of diabetic neurotoxicity.
INTRODUCTION: Uncontrolled chronic hyperglycemia in diabeticpatients could result in various complications, including neurotoxicity. Urtica dioica L. (UD) is known for its hypoglycemic and antioxidant effects. In this study, we evaluated the efficacy of UD and pioglitazone (PIO) in reduction of neurotoxicity and oxidative stress in streptozocin-induced diabeticmice. MATERIALS AND METHODS: Male mice were divided into seven groups: control, diabetic, dimethyl sulfoxide-treated control, PIO-treated, UD-treated, UD-PIO-treated, and vitamin E-treated. For induction of diabetes, streptozocin was injected in a single dose (65 mg/kg, i.p.). All treatments were performed for 5 weeks. Neurotoxicity was evaluated through hot plate and formalin test. Then, animals were killed, brain tissue was separated and the mitochondrial fraction was isolated with different centrifuge technique. Also, oxidative stress markers (reactive oxygen species, lipid peroxidation, protein carbonyl, glutathione) were measured in brain. Mitochondrial function was evaluated by MTT test in brain isolated mitochondria. RESULTS: Elevation of oxidative stress markers and mitochondrial damage were observed in diabeticmice compared to control group. Administration of PIO and UD ameliorated the oxidative stress and mitochondrial damage (p < 0.05) in diabeticmice. Also increase in pain score was shown in diabeticmice that treatment with UD and PIO diminished elevation of pain score in diabeticmice. Interestingly, simultaneous administration of PIO and UD showed synergism effect in attenuation of oxidative stress and hyperglycemia. CONCLUSION:UD showed a therapeutic potential for the attenuation of oxidative stress and diabetes-induced hyperglycemia that can be considered as co-treatment in treatment of diabetic neurotoxicity.