Evaluation of potential protective effects of curcumin versus metformin in experimentally-induced metabolic syndrome in rats

Metabolic syndrome [MetSyn] is the clustering of various interrelated risk factors of metabolic origin that increased incidence of cardiovascular diseases and type 2 diabetes. In this study the effectiveness of curcumin was evaluated in comparison with metformin in fructose-induced MetSyn disease in rats. Fructose was fed [10% solution in drinking water] for 8 weeks during which groups of rats were administered once daily vehicle [2% carboxy methyl cellulose], curcumin [40 and 80 mg/kg], metformin [100 and 200 mg/kg], their combinations and compared with group received tap water instead of fructose. The results revealed that induction of MetSyn was associated with glucose intolerance, insulin resistance alongside with increased weights of body and visceral fats. This was accompanied with an elevation of arterial blood pressure. Meanwhile, it caused disturbances in lipid profile [triglyceride, total cholesterol, HDL-C and LDL-C] and both oxidative stress [inalondialdehyde, 8-Iso-PGF[2alpha] and superoxide dismutase] and inflaminatory status [tumor necrosis factor-a, interleukin-6, C- reactive protein and adiponectin] parameters. Each of curcumin and metformin significantly prevents, to variable extents, the progression of most of these signs of MetSyn. Furthermore, the efficacy of each of the two drugs in question was significantly augmented upon their concurrent administration. These protective effects of the two drugs under investigation presumably may be relevant to their ability to reduce the oxidative stress and to ameliorate the inflammatory processes

Further investigations of the central effects of a calcum-entry blocker [Verapamil]

The intracerebroventricular injection [ICVI] of the selective alpha2- agonist clonidine into anesthetized rabbits produced significant lowering in mean arterial blood pressure [B.P]. However, each of the entry selective - anatagonist yohimbine and the Ca2+ entry blocking agent verapamil produced transient increase in B.P. Pretreatment with yohimbine completely prevented the occurrence of the hypotensive effect of the subsequent dose of clonidine. Similarly, prior administration of verapamil, significantly attenuated clonidine-hypotensive effect. Both yohimbine and verapamil displayed considerable prophylactic activity against ouabain-induced arrhythmias in conscious mice. These results support the suggestion that alpha2- adrenoceptors play a role in the cardiovascular responses of Ca2+ - entry blockers. Verapamil injected intracerebroventricularly but not yothimbine, displayed protective capacity against neurological changes, including the convulsions, induced by central injection of ouabain into conscious mice. These results reflect the wide spectrum of the CNS actions of Ca2+ - entry blocker verapamil compared to those of alpha2- antagonists

Antinociceptive activity of some tricyclic antidepressants

The antinociceptive activities of the tricyclic antidepressants amitriptyline and desipramine were experimentally evaluated in comparison with morphine. For mesurement of analgesia acetic acid stretching test and hot-plate method in mice as well as tail flick procedure in rats were adopted. Amitrityline in a dose of 30 mg/kg i,p. displayed antinocicetive activity in both hot-plate and tail-flick whereas desipramine, failed to exhibit antinociceptive effect in he three different tests used. Morphine showed a marked antinociceptive effect in all the three methods used. Pretreatment of animals for two weeks with daily single dose [5 mg/kg i.p] of either amitriptyline or desipramine has enhanced morphine analgesia in hot-plate and tail-flick procedures. However, the analgesic effect of morphine against acetic acid stretching test was not affected by the subacute pretreatment with the two antidepressant agents. The antinociceptive effect of amitriptyline as assessed by hot-plate test was partly attenuated but not antagonized by prior injection of naloxone in a dose of 3 mg/kg. The possible implication of opiate receptors and the other mechanisms in the analgestic properties of tricyclic antidepressants has been discussed

Some cardiovascular responses elicited by beta-adrenergic antagonists, calcium-entry blockers and their combinations

The present study was carried out on both intact rabbits and isolated perfused rabbit's heart for the assessment of the cardiovascular actions of Ca++ - entery blockers, beta blockers and their combinations. The results indicated that the Ca++ blockers, verapamil and nifedipine and the non selective beta blocker propranolol have a negative inotropic and chronotropic effects on the isolated heart preparation. The selective B-blocker atenolol, depressed the myocardium only in very high dose which is much greater than the therapeutic dose. The combinations of the two groups have an additive negative inotropic and chronotropic actions. The combinations of verapamil with the beta blockers, specially propranolol produced much more negative inotropic effect than when nifedipine was used instead of verapamil. The individual drugs of both groups have a hypotensive effect on the blood pressure [B.P.] of rabbits. The combinations of both groups of the drugs have no additive effect on the B.P. of rabbits. Electrocardiographic monitoring indicated that each verapamil, propranolol, atenolol and their combinations produced bradycardia and prolongation of both P-R and Q-T intervals. Nifedipine caused tachycardia and shortening of Q-T interval. The two groups of drugs produced insignificant changes in the electrolyte levels in serum and cardiac tissue except for Ca++ ion level in the cardiac tissue which was significantly reduced by the individual Ca++ blocking drugs and by their combination with the B-blockers

Two novel pyrazoles derivatives with penicillamine-like activities

The antidotal activities of two positional isomers of dimethyl 1 H-pyrazole carboxylic acid derivatives [GI and GII] were evaluated against copper sulphate [CuSO4] in rats. The antiinflammatory properties of these compounds were determined in rats by the trypan blue method. Penicillamine was used in these experiments as a reference drug for comparative purposes. Median lethal doses [LD 50] of compounds in question were determined in mice. In addition, some pharmacological tests were carried out on the compounds. Results of these studies revealed that both the two compounds exhibited antidotal and anti-inflammatory effectiveness superior than those of penicillamine. Intraperitoneal injection of these compounds did not lead to any remarkable changes in the blood pressure, ECG or respiration of rabbits