Mohammad Dallak

The influence of pulmonary receptors on respiratory drive in a rabbit model of pulmonary emphysema

We have observed that pulmonary rapidly adapting receptor activity is greater in emphysematous rats than in controls. Pulmonary receptor activity, if modified by lung disease, may produce an inappropriate drive to breathe which may be perceived as dyspnoea. To investigate the efferent (drive) component of this hypothesis respiratory drive (phrenic nerve activity) was recorded in a rabbit model of emphysema. Drive was measured as slope and peak height of phrenic nerve activity. Slope and peak height were greater in emphysematous rabbits than controls, by 28% and 34%, respectively. Block of slowly adapting pulmonary stretch receptors by inhaled sulphur dioxide (which left only rapidly adapting and C-fibre receptors active) decreased drive in control (slope: 38.89+/-2.29 to 24.09+/-1.26, P<0.01) but not emphysematous rabbits (slope: 49.92+/-4.11 to 54.51+/-5.28, NS). Subsequent vagotomy decreased drive in emphysematous rabbits (slope: 54.51+/-5.28 to 41.41+/-3.90, P<0.05) but not controls (24.09+/-1.26 to 23.07+/-1.84, NS). Increased rapidly adapting receptor activity may, in part, increase respiratory drive in emphysema. This vagal component is only part of the total increased drive which may be perceived as dyspnoea in man.

Swim exercise inhibits hemostatic abnormalities in a rat model of obesity and insulin resistance

Abstract Background: We sought to determine whether swim exercise can inhibit high carbohydrate and fat diet (HCFD)-induced biomarkers of coagulation and thrombosis. Material and methods: Rats were either fed with HCFD (model group) or a standard laboratory chow (control group) for 15 weeks. Swim exercise-‘treated’ rats started swim exercise training from the 11th week until being sacrificed, on Week 15. Results: HCFD caused a significant increase in blood glucose, insulin resistance (HOMA-IR), lipidemia, and inflammatory biomarkers. In addition, HCFD significantly modulated coagulation and thrombosis biomarkers; fibrinogen, plasminogen activator inhibitor-1, von Willebrand factor, prothrombin time, activated partial thromboplastin time, blood clotting and bleeding time, and ADP-induced platelet aggregation that was effectively inhibited by swimming exercises. Conclusions: We demonstrate that in an animal model of obesity and insulin resistance, there is a significant change in hemostasis, which is ameliorated by swim exercise.

Exercise protects against insulin-dependent diabetes-induced osteoarthritis in rats: A scanning electron microscopy study

ABSTRACT We tested the hypothesis that swim exercise can protect the articular cartilage from damages induced secondary to insulin-dependent diabetes mellitus in rats using the scanning electron microscopy and to monitor the blood levels of oxidative and antioxidative stress biomarkers that are known to be modulated in osteoarthritis (OA). A profound damage to the cartilage was observed in the diabetic rats. Our findings also show that swim exercise protects the knee joints from damage induced by diabetes as well as significantly inhibiting OA-induced upregulation of thiobarbituric acid reactive substances (TBARS) and tumor necrosis factor alpha (TNF-α) and augmented superoxide dismutase (SOD) inhibition by OA. Thus, we demonstrated an effective protection by swim exercise against diabetes-induced OA in a rat model of the disease.

A synergistic protective effect of selenium and taurine against experimentally induced myocardial infarction in rats

Abstract This study investigated the protective effect of subacute pre-adminsitration of either selenium (Se), taurine (Tau), or both drugs in combination against experimentally induced myocardial infarction (MI) in rats and illustrates the possible mechanisms of action. While solely pre-administration of Se or Tau resulted in partial amelioration in all of the measured parameters in MI rats, concomitant administration of both drugs to MI rats significantly restored contractility function by increasing LVSP and decreasing LVEDP and significantly normalized serum levels of LDH, CK-MB and BNP and restored normal cardiac architecture. This concomitant treatment acted by increasing the activity of major antioxidant enzymes (SOD and GPx), decreasing the levels of inflammatory markers including TNF-α, IL-6 as well as levels of Bcl-2 and caspase-3 and downregulating mRNA levels of Bax and P53, markers of apoptosis. In conclusion, a combination of Se and Tau provides a new strategy to alleviate MI-induced cardiac dysfunction.

Unacylated ghrelin stimulates steroidogenesis in lean rats and reverses reproductive dysfunction in high fat diet-fed rats

ABSTRACT This study investigated the effect of sub-chronic administration of unacylated ghrelin (UAG) on steroidogenesis, sperm parameter, and reproductive function in lean and high fat diet (HFD)-induced obese male rats. Rats were divided into 4 groups (n = 12 each) as 1) Control-fed standard diets (STD): (10 kcal%), 2) STD + UAG (200 ng/kg, i.p.), 3) HFD obese: fed HFD (45 kcal%), and 4) HFD + UAG. Diet regimen was continued for 16 weeks after which normal saline as a vehicle or UAG was administered to desired groups for the next 4 weeks. In vitro, testicular slices were incubated with increasing concentrations of UAG (10−8–10−6 M) in the presence or absence of GSH-R1a antagonist, [D-Lys-3]-GHRP-6 (10−6 M). UAG significantly increased the circulatory levels of FSH, LH and testosterone, increased testicular testosterone levels and sperm count and motility in lean and obese rats and reduced sperm morphological abnormalities and increased pregnancy rate and number of pups at birth in HFD-obese rats. Associated with the reduction in the final body and fat masses weights and independent of food intake, UAG post-therapy to both lean and HFD-fed rats significantly lowered fasting blood glucose and insulin levels, lowered HOMA-IR value, enhanced OGTT and ITT, lowered circulatory leptin levels, downregulated aromatase expression in adipose and testicular tissue and inhibited HFD-induced testicular oxidative stress and activation of cleaved caspase-3. Dysregulation of testicular levels of StAR, SF-1, CYP11A1 in the testis of both groups as well as in the in vitro preparation, in a dose-dependent manner, independent of GSH-R1a and not associated with activation of STAT3, a mediator of leptin signaling was apparent. In conclusion, administration of UAG can enhance reproductive function in lean rats and reverses HFD-induced reproductive dysfunction in obese rats. Abbreviations: AG: acylated ghrelin; BMI: body mass index; CHOL: cholesterol;FSH: follicular stimulating hormone; GHS: growth hormone secretagogues; GSH: reduced glutathione; HFD: high fat diet; HOMA-IR: homeostasis model assessment of insulin resistance: IR: insulin resistance; OGTT: oral glucose tolerance test; ITT: insulin tolerance test; LH: luteinizing hormone; MDA: malondialdehyde; STAT3: signal transducer and activator of transcription; SOD: superoxide dismutase; STD: standard diet; SF-1: steroidogenic factor-1; StAR: steroidogenic acute regulatory protein; CYP11A1: cholesterol side-chain cleavage enzyme (or P450scc); TGs: triglycerides; UAG: unacylated ghrelin.

Metformin Pretreatment Ameliorates Diabetic Nephropathy Induced by a Combination of High Fat Diet and Streptozotocin in Rats

Kidney injury secondary to diabetes is the most common cause of kidney failure. We sought to determine whether pretreatment with the insulin-sensitizing drug metformin prior to the induction of diabetes can protect the kidney against the development of diabetic nephropathy (DN) induced by a combination of a high-fat diet and streptozotocin. Rats were either injected with veh icle (control group) or with a single injection of streptozotocin (STZ) (50 mg/kg) two weeks after being fed on a high-fat diet (HFD ) (model group) and continued on HFD until being sacrificed 10 weeks post diabetic induction. The protective group that also fed on a HF D f r 12 weeks was put on metformin (200 mg/kg/day) two weeks before STZ injection and continued on metformin until the sacrifice day. Harvested kidney tissues were examined by light microscopy after staining with hematoxylin and eosin (H&E) and periodic acid Sc h ff (PAS). Blood samples were assayed for sugar, urea, creatinine, and biomarkers of inflammation. Compared to a normal tissue hist ology in the control group, there was a profound damage to the kidney in the model group as demonstrated by markedly dilated capsular spa e, increased mesangial matrix expansion, congested blood vessels, and many tubular epithelial cells showing small pyknotic nuclei and vacuolated cytoplasm, which were significantly but not completely protected by metformin. Our findings also show that metformin significantly inhibited the inflammatory biomarkers, tumor necrosis factor-alpha (TNFα) and C-reactive protein (CRP) induced by diabetes and HFD as well as significantly inhibiting blood sugar, urea, and creatinine. However, the levels of TNFα, CRP, glucose, and creatinine in the metformin-treated group was still significant to the control group. Thus, we demonstrated an efficient but no t complete protection by metformin pretreatment against DN induced by a combination of HFD and streptozotocin in rats.