Impact of L-Arginine on diabetes-induced neuropathy and myopathy: Roles of PAI-1, Irisin, oxidative stress, NF-κß, autophagy and microRNA-29a.

BACKGROUND: T2DM is a chronic disorder with progressive neuromuscular alterations. L-arginine (ARG) is the most common semi-essential amino acid having several metabolic functions. AIM: to investigate the impact of L-arginine in combating diabetic-induced neuromyopathy and its possible mechanisms. MATERIALS & METHODS: 24 rats were divided into CON, CON+ARG, DC, DC+ARG. Behavioral tests, Body weight (BW), fasting blood glucose (FBG), insulin, total antioxidant capacity (TAC), malondialdehyde (MDA), plasminogen activator inhibitor-1 (PAI-1), and irisin were done. Creatine kinase-MM (CK-MM), interleukin 4 (IL-4), interleukin 6 (IL-6), TAC, MDA, expression of microRNA-29a mRNA & light chain 3 protein were determined in muscle. Histological and NF-κß immunohistochemical expression in muscle and nerve were assessed. RESULTS: ARG supplementation to diabetic rats improved altered behavior, significantly increased BW, insulin, TAC, irisin and Il-4, decreased levels of glucose, microRNA-29a, NF-κß and LC3 expression, PAI-1, CK-MM and restored the normal histological appearance. CONCLUSIONS: ARG supplementation potently alleviated diabetic-induced neuromuscular alterations.

Pioglitazone and/or irbesartan ameliorate COPD-induced endothelial dysfunction in side stream cigarette smoke-exposed mice model.

AIMS: Cigarette smoking (CS) is the main cause of chronic obstructive pulmonary disease (COPD). Endothelial dysfunction is related to the severity of pulmonary disease in COPD. This study aimed to evaluate the effectiveness of single and combined administration of pioglitazone (Pio) and irbesartan (Irb) against COPD-induced endothelial dysfunction in mice and the involvement of NO and H2S in their effects. MATERIALS AND METHODS: Adult male Swiss mice (n = 40, weighing 25-30 g) were assigned into 5 groups. The normal control group received 1% carboxy methyl cellulose (CMC). The CS group was exposed to CS and administered 1% CMC for 3 months. The CS + Pio, CS + Irb, and CS + Pio/Irb groups were subjected to CS and received Pio (60 mg/kg), Irb (50 mg/kg), and their combination respectively, daily orally for 3 months. Body weight gain, mean blood pressure, urinary albumin, serum NO and ET-1 levels with TNF-α and IL-2 levels in lung tissue and bronchoalveolar lavage were measured. Lung H2S and ET-1 levels, protein expression of PPARγ in lung and VEGF in lung and aortic tissues with histological changes were assessed. KEY FINDINGS: Our results illustrated that CS induced a model of COPD with endothelial dysfunction in mice. Pio/Irb singly and in combination elicited protective effects against the pathophysiology of the disease with more improvement in the combined group. There is a strong correlation between NO and H2S as well as the other measured parameters. SIGNIFICANCE: Collectively, both drugs performed these effects via their anti-inflammatory potential and increasing H2S and NO levels.

Garlic (Allium sativum) exhibits a cardioprotective effect in experimental chronic renal failure rat model by reducing oxidative stress and controlling cardiac Na+/K+-ATPase activity and Ca2+ levels.

Gentamicin (GNT)-induced nephrotoxicity culminates into renal failure with a possible cardiovascular impact. Garlic extract (GE) is a cardiovascular protectant with limited mechanistic data. Therefore, we assessed the disturbance in specific cardiac parameters and the potential protective effect of GE supplementation against them in a rat model of GNT-induced chronic renal failure (CRF). Adult male rats (n = 24) were randomly assigned into four groups (n = 6 each): normal controls (CON), garlic extract controls (GE; 250 mg kg-1, orally), GNT-induced CRF (GNT; 100 mg kg-1, i.p.), and GNT + GE (GNT and GE in the same previous doses) groups. GNT and GE were given daily for 3 weeks. Animals co-treated with GNT and GE exhibited improved renal functions, body weight (BW), and heart weight (HW)/BW ratio; declined blood pressure; lowered plasma levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and total peroxides (TP); and elevated total antioxidant capacity (TAC) levels. Moreover, the heart tissue contained raised levels of TAC and Na+/K+-ATPase activity and lowered levels of TP and Ca2+. Findings provide evidence that administration of GE in experimental CRF model helped protect the heart through reducing oxidative stress and controlling cardiac Na+/K+-ATPase activity and Ca2+ levels.

The role of ITPA and ribavirin transporter genes polymorphisms in prediction of ribavirin-induced anaemia in chronic hepatitis C Egyptian patients.

Few data are available concerning the roles of polymorphisms of inosine triphosphatase (ITPA) gene and ribavirin (RBV) transporter genes in the prediction of RBV-induced anaemia among Egyptians with chronic hepatitis C (CHC). Genotyping of three ITPA gene variants and two variants of RBV transporter genes has been performed in 123 patients under pegylated interferon-α/ribavirin treatment. The baseline haemoglobin and ITPA rs1127354 CA/AA have been found as predictors of anaemia at 4, 8 and 12 weeks of RBV therapy. In addition, ITPA rs7270101 AC/CC and age predicted anaemia after 12 weeks of therapy. In conclusion, the ITPA variant rs1127354C>A significantly predict RBV-induced anaemia during the first 3 months of treatment and it is recommended to be assessed before RBV administration.