title: The combined effect of metformin and L-cysteine on inflammation, oxidative stress and insulin resistance in streptozotocin-induced type 2 diabetes in rats.
abstract: Increasing evidence has established causative links between obesity, chronic inflammation and insulin resistance; the core pathophysiological feature in type 2 diabetes mellitus. This study was designed to examine whether the combination of L-cysteine and metformin would provide additional benefits in reducing oxidative stress, inflammation and insulin resistance in streptozotocin-induced type 2 diabetes in rats. Male Wistar rats were fed a high-fat diet (HFD) for 8 weeks to induce insulin resistance after which they were rendered diabetic with low-dose streptozotocin. Diabetic rats were treated with metformin (300 mg/kg/day), L-cysteine (300 mg/kg/day) and their combination along with HFD for another 2 weeks. Control rats were fed normal rat chow throughout the experiment. At the end of treatment, fasting blood glucose, fasting serum insulin, homeostasis model assessment-insulin resistance index (HOMA-IR) and serum free fatty acids (FFAs) were measured. Serum levels of the inflammatory markers; monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP) and nitrite/nitrate were also determined. The liver was isolated and used for determination of malondialdehyde (MDA), reduced glutathione (GSH), caspase-3 and cytochrome c levels. The hypoglycemic effect of the combination therapy exceeded that of metformin and L-cysteine monotherapies with more improvement in insulin resistance. All treated groups exhibited significant reductions in serum FFAs, oxidative stress and inflammatory parameters, caspase-3 and cytochrome c levels compared to untreated diabetic rats with the highest improvement observed in the combination group. In conclusion, the present results clearly suggest that L-cysteine can be strongly considered as an adjunct to metformin in management of type 2 diabetes.
authors.affiliation: Medical Research Institute, University of Alexandria, 165 Horreya Avenue, Alexandria, Egypt.
authors.forename: Zenat K
authors.initials: ZK
authors.lastname: Salman
authors.forename: Rowaida
authors.initials: R
authors.lastname: Refaat
authors.forename: Eman
authors.initials: E
authors.lastname: Selima
authors.forename: Ashgan
authors.initials: A
authors.lastname: El Sarha
authors.forename: Menna A
authors.initials: MA
authors.lastname: Ismail
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D003545:Cysteine / Q000494:pharmacology* / Q000627:therapeutic use; D045304:Cytochromes c / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004347:Drug Interactions; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018932:Chemokine CCL2; D005230:Fatty Acids, Nonesterified; D009566:Nitrates; D009573:Nitrites; D008315:Malondialdehyde; D002097:C-Reactive Protein; D045304:Cytochromes c; D008687:Metformin; D053148:Caspase 3; D005978:Glutathione; D003545:Cysteine
keywords: Insulin resistance; Metformin; Streptozotocin-induced type 2 diabetes; l-Cysteine