Badreldin H. Ali

Biological effects of gum arabic: a review of some recent research.

Gum arabic (GA) is a branched-chain, complex polysaccharide, either neutral or slightly acidic, found as a mixed calcium, magnesium and potassium salt of a polysaccharidic acid. The backbone is composed of 1,3-linked beta-D-galactopyranosyl units. The side chains are composed of two to five 1,3-linked beta-D-galactopyranosyl units, joined to the main chain by 1,6-linkages. Pharmacologically, GA has been claimed to act as an anti-oxidant, and to protect against experimental hepatic-, renal- and cardiac toxicities in rats. These reports could not be confirmed by others. GA has been claimed to alleviate the adverse effects of chronic renal failure in humans. This could not be corroborated experimentally in rats. Reports on the effects of GA on lipid metabolism in humans and rats are at variance, but mostly suggest that GA ingestion can reduce plasma cholesterol concentrations in rats. GA has proabsorptive properties and can be used in diarrhoea. It enhances dental remineralization, and has some antimicrobial activity, suggesting a possible use in dentistry. GA has been shown to have an adverse effect on electrolyte balance and vitamin D in mice, and to cause hypersensitivity in humans. More studies are needed before the pharmacological properties of GA can be utilized in therapy.

The acute proinflammatory and prothrombotic effects of pulmonary exposure to rutile TiO2 nanorods in rats.

Nanotechnology is extensively used in industry and is widely explored for possible applications in medicine. However, its potential respiratory and systemic adverse effects remain unknown. Here pure titanium dioxide (TiO2) nanorods with rutile structure were prepared at room temperature by using a soft chemistry technique. The structure of the TiO2 rutile nanorods was confirmed by powder X-ray diffraction, and the size was revealed by transmission electron microscopy. Thereafter, we investigated, in Wistar rats, the acute (24-hr) effects of intratracheal instillation of these rutile TiO2 nanorods (1 and 5 mg/kg) on lung inflammation (assessed by bronchoalveolar lavage), systemic inflammation, and platelet aggregation in whole blood. Compared with vehicle-exposed rats, rats that underwent intratracheal instillation of TiO2 nanorods experienced a dose-dependent increase in macrophage numbers at 1 (+50%) and 5 mg/kg (+81%; P < 0.05) and an influx of neutrophils at 1 (+294%) and 5 mg/kg (+4117%; P < 0.01) in their bronchoalveolar lavage fluid. Both doses of rutile TiO2 nanorods caused pulmonary and cardiac edema, assessed by analysis of the wet weight–to–dry weight ratios. Similarly, the numbers of monocytes and granulocytes in the blood were increased in a dose-dependent manner after exposure to rutile TiO2 nanorods. In contrast, the number of platelets was significantly reduced after pulmonary exposure to 5 mg/kg TiO2 nanorods; this result indicated the occurrence of platelet aggregation in vivo. The direct addition of TiO2 nanorods (0.4–10 μg/ml) to untreated rat blood significantly induced platelet aggregation in a dose-dependent fashion in vitro. It is concluded that the intratracheal instillation of rutile TiO2 nanorods caused upregulation of lung inflammation, pulmonary and cardiac edema, and systemic inflammation. Rutile TiO2 nanorods also triggered platelet aggregation in vivo and in vitro.

Experimental gentamicin nephrotoxicity and agents that modify it: a mini-review of recent research.

The aminoglycoside antibiotic gentamicin (GM) is still widely used against infections by Gram-positive and Gram-negative aerobic bacteria. Its therapeutic efficacy, however, is limited by renal impairment that occurs in up to 30% of treated patients. The drug may accumulate in epithelial tubular cells causing a range of effects starting with loss of the brush border in epithelial cells and ending in overt tubular necrosis, activation of apoptosis and massive proteolysis. GM also causes cell death by generation of free radicals, phospholipidosis, extracellular calcium-sensing receptor stimulation and energetic catastrophe, reduced renal blood flow and inflammation. Many drugs have been shown to either ameliorate or potentiate GM nephrotoxicity. This article aims at updating the literature that has been published in the past decade on the effects of agents that either ameliorate or augment the nephrotoxicity of this aminoglycoside. Notable among the new ameliorating procedures are gene therapy, such as intravenous cell therapy with serum amyloid A protein-programmed cells, and the use of some novel antioxidant agents and oils of natural origin. These include, for example, green tea, garlic saffron, grape seed extracts as well as sesame and oleanolic oils. Agents that may augment GM nephrotoxicity include indomethacin, cyclosporin, uric acid and the Ca(++) -channel blocker verapamil. Most of the nephroprotective agents mentioned here have not been tested in large controlled clinical trials. Because of their relative safety and effectiveness, antioxidant agents seem to be good candidates for testing in humans.

Some pharmacological studies on Artemisia herba-alba (Asso.) in rabbits and mice

The aqueous extract of Artemisia herba-alba Asso. (Compositae) produced an initial hyperglycaemia which was followed by hypoglycaemia in normoglycaemic and alloxan-treated rabbits and mice. The extract (0.39 g/kg) significantly increased gastrointestinal transit time and the reaction time to thermal stimuli but had no effect on the activity of alkaline phosphatase or concentrations of creatinine and urea in plasma. Histopathological examination indicated mild hydropic degeneration in hepatocytes and proximal convoluted tubules. The duodenum showed mild oedema of the substantia of the mucosal propria. The plant extract showed weak antimicrobial activity.

Curcumin has a palliative action on gentamicin-induced nephrotoxicity in rats

Generation of free radicals in kidney cortex plays an important role in the pathogenesis of gentamicin (GM) nephrotoxicity, and curcumin, the yellow curry pigment isolated from turmeric, has been confirmed to have a strong antioxidant action. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of curcumin on GM nephrotoxicity. Curcumin was given to rats at an oral dose of 200 mg/kg/day for 10 days, and in some of these rats GM was also injected intramuscularly at a dose of 80 mg/kg/day during the last 6 days of the treatment. Nephrotoxicity was evaluated histopathologically by light microscopy, and biochemically by measuring the concentrations of creatinine and urea in serum, and reduced glutathione (GSH) concentration and superoxide dismutase (SOD) activity in renal cortex. The concentration of GM in renal cortex was measured microbiologically. GM significantly increased the concentrations of urea and creatinine (P < 0.05) by about 111 and 97%, respectively. GM treatment reduced cortical GSH concentration by about 31% (P < 0.05), and the activity of SOD by about 27% (P < 0.05). Curcumin significantly mitigated these effects. Sections from saline and curcumin‐treated rats showed apparently normal proximal tubules. However, kidneys of GM‐treated rats had a moderate degree of necrosis. The degree of necrosis appeared lessened when GM was given simultaneously with curcumin. The concentration of GM in the renal cortex of the rats given GM + curcumin was significantly (P < 0.05) lower than that found in rats treated with GM alone by about 39%. The results suggested that curcumin had ameliorated the histopathological and biochemical indices of nephrotoxicity in rats. Pending further studies, curcumin may potentially be useful as a nephroprotectant agent.

Contrasting actions of diesel exhaust particles on the pulmonary and cardiovascular systems and the effects of thymoquinone

BACKGROUND AND PURPOSE Acute exposure to particulate air pollution has been linked to acute cardiopulmonary events, but the underlying mechanisms are uncertain.

Effect of Gum Arabic on Oxidative Stress and Inflammation in Adenine–Induced Chronic Renal Failure in Rats

Inflammation and oxidative stress are known to be involved in the pathogenesis of chronic kidney disease in humans, and in chronic renal failure (CRF) in rats. The aim of this work was to study the role of inflammation and oxidative stress in adenine-induced CRF and the effect thereon of the purported nephroprotective agent gum arabic (GA). Rats were divided into four groups and treated for 4 weeks as follows: control, adenine in feed (0.75%, w/w), GA in drinking water (15%, w/v) and adenine+GA, as before. Urine, blood and kidneys were collected from the rats at the end of the treatment for analysis of conventional renal function tests (plasma creatinine and urea concentration). In addition, the concentrations of the pro-inflammatory cytokine TNF-α and the oxidative stress markers glutathione and superoxide dismutase, renal apoptosis, superoxide formation and DNA double strand break frequency, detected by immunohistochemistry for γ-H2AX, were measured. Adenine significantly increased the concentrations of urea and creatinine in plasma, significantly decreased the creatinine clearance and induced significant increases in the concentration of the measured inflammatory mediators. Further, it caused oxidative stress and DNA damage. Treatment with GA significantly ameliorated these actions. The mechanism of the reported salutary effect of GA in adenine-induced CRF is associated with mitigation of the adenine-induced inflammation and generation of free radicals.

Pulmonary exposure to diesel exhaust particles promotes cerebral microvessel thrombosis: Protective effect of a cysteine prodrug l-2-oxothiazolidine-4-carboxylic acid

Inhaled particulate matter is associated with increased cerebro- and cardiovascular events. However, the systemic mechanisms underlying these effects remain unclear. In the present study, we investigated the mechanisms underlying the relationship between airway and systemic inflammation and pial cerebral venular thrombosis, 24h after intratracheal (i.t.) instillation of diesel exhaust particles (DEP; 15 or 30 microg/mouse) or saline (control). Doses of 15 and 30 microg/mouse induced a dose-dependent macrophage and neutrophil influx into the bronchoalveolar lavage (BAL) fluid with elevation of total proteins and Trolox equivalent antioxidant capacity (TEAC), but without IL-6 release. Similarly, in plasma, IL-6 concentrations did not increase but the TEAC was significantly and dose-dependently decreased. The number of platelets and the tail bleeding time were both significantly reduced after exposure to DEP (30 microg). Interestingly, the same dose showed platelet proaggregatory effect in mouse pial cerebral venules. Pretreatment with the cysteine prodrug l-2-oxothiazolidine-4-carboxylic acid (OTC, 80 mg/kg) 24 and 1h before i.t. DEP (30 microg), abolished the DEP-induced macrophage and neutrophil influx, and the increase of TEAC in BAL. Lung histopathology confirmed the protective effect of OTC on DEP-induced lung inflammation. OTC also reversed the decrease of TEAC concentrations in plasma, the shortening of the bleeding time, and the thrombotic effect of DEP in pial cerebral venules. We conclude that pulmonary exposure to DEP cause oxidative stress responsible, at least partially, for the pulmonary and systemic inflammation and thrombotic events in the pial cerebral microvessels of mice. OTC pretreatment abrogated these effects through its ability to balance oxidant-antioxidant status.

Protective Effect of Curcumin on Pulmonary and Cardiovascular Effects Induced by Repeated Exposure to Diesel Exhaust Particles in Mice

Particulate air pollution has been associated with increased risk of cardiopulmonary diseases. However, the underlying mechanisms are not fully understood. We have previously demonstrated that single dose exposure to diesel exhaust particle (DEP) causes lung inflammation and peripheral thrombotic events. Here, we exposed mice with repeated doses of DEP (15µg/animal) every 2nd day for 6 days (a total of 4 exposures), and measured several cardiopulmonary endpoints 48 h after the end of the treatments. Moreover, the potential protective effect of curcumin (the yellow pigment isolated from turmeric) on DEP-induced cardiopulmonary toxicity was assessed. DEP exposure increased macrophage and neutrophil numbers, tumor necrosis factor α (TNF α) in the bronchoalveolar lavage (BAL) fluid, and enhanced airway resistance to methacoline measured invasively using Flexivent. DEP also significantly increased plasma C-reactive protein (CRP) and TNF α concentrations, systolic blood pressure (SBP) as well as the pial arteriolar thrombosis. It also significantly enhanced the plasma D-dimer and plasminogen activator inhibitor-1 (PAI-1). Pretreatment with curcumin by oral gavage (45 mg/kg) 1h before exposure to DEP significantly prevented the influx of inflammatory cells and the increase of TNF α in BAL, and the increased airway resistance caused by DEP. Likewise, curcumin prevented the increase of SBP, CRP, TNF α, D-dimer and PAI-1. The thrombosis was partially but significantly mitigated. In conclusion, repeated exposure to DEP induced lung and systemic inflammation characterized by TNFα release, increased SBP, and accelerated coagulation. Our findings indicate that curcumin is a potent anti-inflammatory agent that prevents the release of TNFα and protects against the pulmonary and cardiovascular effects of DEP.

Effects of Gum Arabic in rats with adenine-induced chronic renal failure:

Gum Arabic (GA [Acacia senegal]) is reputed, in Arabian medicinal practices, to be useful in treating patients with chronic renal failure (CRF), albeit without strong scientific evidence. We have previously shown that GA had no significant effect in rats with CRF induced by surgical nephrectomy. Here, we used another animal model of human CRF (feeding adenine at a concentration of 0.75%w/w for four weeks) to test the effect of GA on CRF. Renal morphology and measurements of plasma concentrations of urea and creatinine (Cr), and Cr clearance, in addition to urinary volume, osmolarity and protein concentrations, and N-acetylglucosamine and lactate dehydrogenase activities were performed. Interleukin-6 and the total antioxidant levels in urine, as well as the activity of superoxide dismutase in renal tissues, were estimated. Adenine feeding resulted in marked renal damage. GA (6%w/v and 12%w/v in drinking water for four consecutive weeks) significantly ameliorated the adverse biochemical alterations indicative of renal failure, abated the decrease in body weight and reduced the glomerular, tubular and interstitial lesions induced by adenine. Our study provides evidence that GA attenuated renal dysfunction in this model of CRF, suggesting a promising potential for it in protecting against renal failure progression. The mechanism(s) of this nephroprotection is uncertain but may involve anti-oxidant and/or anti-inflammatory actions.