Metformin-attenuated sepsis-induced oxidative damages: a novel role for metformin

Document Type: Original Article

Authors

1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran

2 Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran

3 Iranian Evidence-Based Medicine Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran

4 Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

5 Medical Education Research Center, Health Management and safety Promotion Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran

6 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

7 Clinical Pharmacy (Pharmacotherapy) Department, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Objective(s): Sepsis can result in severe organ injury by provoking inflammatory cascades and oxidative stress. Several studies are currently underway to find a drug with anti-inflammatory effects to prevent mortality and morbidity during sepsis. The present study was undertaken to assess the effects of metformin on oxidative stress and antioxidant status in sepsis induced by the Cecal Ligation and Puncture (CLP) method.
Materials and Methods: Male Wistar rats were divided into 4 groups (n=10): sham, CLP, and 50 and 100 mg/kg metformin-treated CLP groups. After 12 hr, blood samples were collected and lung tissue was removed for histopathological study to detect tissue damage and degree of inflammation based on neutrophil infiltration and assay of the oxidative stress biomarkers superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA), myeloperoxidase (MPO), glutathione peroxidase (GPx), and plasminogen activator inhibitor‐1 (PAI‐1).
Results: The MPO activity and MDA level were decreased in the metformin-treated groups (P<0.05). Moreover, the groups receiving metformin showed lower inflammation scores than the CLP group (P<0.05). No significant differences in SOD, GPx, or PAI in the different groups were observed. The TAC level was reduced in the CLP group compared to the sham group (P<0.05), and interestingly, this value was reduced even further in the metformin-treated groups (PConclusion: It was concluded that metformin protects lung tissue against sepsis-induced oxidative damage, and this protective effect may be more related to its anti-inflammatory and reduced neutrophil accumulation and less to its anti-oxidative properties.

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Main Subjects


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