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.

Protective Effect of Ginkgo biloba and Magnetized Water on Nephropathy in Induced Type 2 Diabetes in Rat.

We aimed in our current study to explore the protective effect of Ginkgo biloba (GB) and magnetized water (MW) against nephrotoxicity associating induced type 2 diabetes mellitus in rat. Here, we induced diabetes by feeding our lab rats on a high fat-containing diet (4 weeks) and after that injecting them with streptozotocin (STZ). We randomly divided forty rats into four different groups: nontreated control (Ctrl), nontreated diabetic (Diabetic), Diabetic+GB (4-week treatment), and Diabetic+MW (4-week treatment). After the experiment was finished, serum and kidney tissue samples were gathered. Blood levels of glucose, triglycerides, cholesterol, creatinine, and urea were markedly elevated in the diabetic group than in the control group. In all animals treated with GB and MW, the levels of urea, creatinine, and glucose were significantly reduced (all P < 0.01). GB and MW attenuated glomerular and tubular injury as well as the histological score. Furthermore, they normalized the contents of glutathione reductase and SOD2. In summary, our data showed that GB and MW treatment protected type 2 diabetic rat kidneys from nephrotoxic damages by reducing the hyperlipidemia, uremia, oxidative stress, and renal dysfunction.

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.

Vitamin D reduces high-fat diet induced weight gain and C-reactive protein, increases interleukin-10, and reduces CD86 and caspase-3.

Obesity can be associated with dysfunction of the immune system. An increased risk of obesity has been reported among individuals with low levels of vitamin D. However, much is still unknown about the link between vitamin D and dysfunction of the spleen and immune system in obesity. Therefore, the objectives of this study were to evaluate the effects of a high-fat diet (HFD) on the spleen and immune system and to determine the protective effects of chronic treatment with vitamin D in reversing the detrimental effects of HFD. Body weight (BW) gain, the serum levels of calcium, C-reactive protein (CRP), and interleukin-10 (IL-10), and the expression of both CD86 and caspase-3 in the spleen were investigated. Twenty-four adult male Wistar rats were divided into three equal groups: the control (C) group received a control diet for 10 weeks, the HFD-C group received a HFD for 10 weeks, and the HFD-treated group received a HFD co-administered with oral vitamin D (1µg/kg) daily for 10 weeks. Administration of vitamin D in combination with HFD significantly decreased BW gain, decreased the serum levels of both calcium and CRP, increased the serum level of IL-10, improved the general histological appearance of the spleen, and decreased the expression of both CD86 and caspase-3 in the spleen in comparison with results seen in the HFD-C group. Our data suggest that vitamin D supplementation holds promise as an adjunct treatment to alleviate the dysfunction of the spleen and immune system commonly seen in HFD-induced obesity.

The effect of omega-3 on cognition in hypothyroid adult male rats.

Thyroid hormones and omega-3 are essential for normal brain functions. Recent studies have suggested that omega-3 may protect against the risk of dementia. The aim of this study was to investigate the effect of hypothyroidism on spatial learning and memory in adult male rats, the underlying mechanisms and the possible therapeutic value of omega-3 supplementation. Thirty male rats were divided into three groups; control, hypothyroid and omega-3 treated. Hypothyroidism induced significant deficits in working and reference memories in radial arm maze, retention deficits in passive avoidance test and impaired intermediate and long-term memories in novel object recognition test. Serum total antioxidant capacity (TAC) and hippocampal serotonin and γ-aminobutyric acid (GABA) levels were decreased in the hypothyroid group as compared to the control group. Moreover, the hippocampus of hypothyroid rats showed marked structural changes as diffuse vacuolar degeneration and distortion of the pyramidal cells. Immunohistochemistry showed that the expression of Cav1.2 (the voltage dependent LTCC alpha 1c subunit) protein was increased in the hypothyroid group as compared to the control group. Omega-3 supplementation ameliorated memory deficits, increased TAC, decreased the structural changes and decreased the expression of Cav1.2 protein. In conclusion omega-3 could be useful as a neuroprotective agent against hypothyroidism-induced cognitive impairment.