ABSTRACT
BACKGROUND: Patients with diabetes mellitus (DM) are at risk of experiencing chronic complications such as retinopathy, nephropathy and myopathy. We aimed to evaluate the effects of L-carnitine on type II DM (T2DM)-induced biochemical, contractile and pathological changes in skeletal muscles of rats. METHODS: Thirty-two male Sprague Dawley rats were divided into the control, control+L-carnitine, T2DM and T2DM+L-carnitine groups. Plasma levels of glucose, insulin, malondialdehyde and antioxidants such as reduced glutathione, catalase and superoxide dismutase, haemoglobin A1c (HbA1c), insulin sensitivity index (ISI) as well as the contractile properties of the gastrocnemius muscle were measured. Also, histopathological studies and immunohistochemical examination of the gastrocnemius muscle using the MuRF1 (muscle RING-finger protein-1) marker were performed. RESULTS: In diabetic rats, malondialdehyde, glucose, insulin, HbA1c and MuRF1 were increased, whereas ISI and antioxidants were decreased and the contractile properties deteriorated. L-carnitine decreased malondialdehyde, glucose, insulin, HbA1c and MuRF1 and increased ISI and antioxidants. Also, L-carnitine improves the contractile properties in diabetic rats. Histopathological studies confirm our data. CONCLUSIONS: We conclude that L-carnitine exhibits protective effects on skeletal muscles of T2DM rats through its hypoglycemic and antioxidant actions as well as its inhibitory effect on protein degradation.
Subject(s)
Carnitine/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Muscle, Skeletal/drug effects , Animals , Antioxidants/metabolism , Catalase/metabolism , Diabetes Mellitus, Experimental/metabolism , Glucose/metabolism , Glutathione/metabolism , Glycated Hemoglobin/metabolism , Hypoglycemic Agents/pharmacology , Insulin/metabolism , Insulin Resistance/physiology , Male , Malondialdehyde/metabolism , Muscle Contraction/drug effects , Muscle Proteins/metabolism , Muscle, Skeletal/metabolism , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolismABSTRACT
OBJECTIVES: To study the effects of darbepoetin-α (DPO-α) (erythropoietin analog) on adriamycin (ADR)-induced chronic nephropathy in rats. METHODS: Sixty-nine male Sprague-Dawley rats divided into 3 groups (23 rats each): negative control group: normal rats received saline as a vehicle; positive control (ADR) group: rats received 2 iv injection of ADR via penile vein at 14-day interval without treatment; and DPO-α group: as ADR group but rats received sc DPO-α (0.3 µg/kg bw) once weekly for 12 weeks. By the end of experiment hemoglobin (Hb) content, serum creatinine, BUN, albumin, triglycerides and cholesterol, urinary protein excretion and kidney injury molecule-1 (KIM-1). GSH, malondialdehyde, caspase-3 expression histopathological and electron microscopic examinations for kidney tissues were done. RESULTS: DPO-α significantly improved the animal survival rate and body weight, Hb, serum BUN, triglycerides, cholesterol, and albumin and urinary protein excretion and KIM-1 in urine. Also, administration of DPO-α improved the morphological damage in glomeruli and renal tubules as well as caspase-3 expression and markers of oxidative stress in kidney tissues. CONCLUSION: Administration of DPO-α alleviates ADR nephropathy and this might due to improvement of Hb content, hyperlipidemia, enhancement of endogenous antioxidants, reduction of apoptosis and tubulointerstitial injury and maintaining the integrity of glomerular membrane.
