Study of the possible protective effects of Nigella sativa on some experimentally induced cardiac, renal and liver diseases in rats

This work was designed to declare the possible protective effects of Nigella sativa "crushed seeds" on experimentally induced renal hypertension, myocardial infarction, renal and hepatic toxicities in male albino rats. The results of the present study demonestrated that Nigella sativa. [N.S] orally for four weeks [l80mg/kg/day] produced significant diastolic hypotensive effect in control normal rats and prevented development of renal hypertension when was administered simultaneously with left renal artery ligation in rats. This hypotensive effect of N.S most probably may be due to inhibition of Ca[++] ion entry via slow Ca[++] channels, inhbition of eicosanoids synthesis and increase release of endothelium derived relaxing factors. However, oral pretreatment with N.S for 4 weeks did not produce significant protective effect in isoprenaline-induced myocardial infarction. Simultaneous administration of N.S with gentamicin sulphate [60mg/kg SC once/day] produced signficant protective effect on renal functions manifested by reduction in serum levels of urea and creatinine [as indicators for kidney function]. This may be explained on the ability of N.S to act as free radical scavenger and to stimulate DNA and protein synthesis that improve tissue regeneration. Additionally, enhanced glutathione, DNA and protein synthesis can explain the protective effect of N.S against acetaminophen-induced hepatotoxicity in rats. Furthermore, N.S significantly decreased the renal and hepatic histopathological toxic changes induced by gentamicin or acetaminophen respectively, but did not be able to normalize them long term administration of N.S may modulate the reactivity of the blood vessels to different endogenous vasoactive agents which may be the cause of renal hypertension and may be also used in the prophylaxis against drugs-induced nephrotoxicity and hepatotoxicity. Accordingly, N.S as a medicinal plant has wide range of health promotion and can play a role in the prophylaxis against drugs induced organs toxicity

Pharmacological effect of diazepam on uterine smooth musciles in non-pregnant and pregnant rats

The effect of diazepam on spontaneous uterine contractility was studied in-situ in both non-pregnant rats and pregnant rats at days 20 of gestation [GD20]. The effect of these drugs were given 15 minutes after injection of diazepam. The uterine response was identified in terms of frequency [number of bursts/10 minutes] and amplitude [micro V/10 minutes] of uterine contraction. Diazepam [0.25-4 mg/kg i.v.] showed significant [P < 0.05], dose-dependent tocolytic effect in both non-regnant and pregnant rats with greater effect in pregnant rats as reflected by greater reduction of both frequency and amplitude of uterine contraction. The dose of diazepam that produced 50% reduction in the amplitude of uterine contraction [ID50] in non-pregnant rats was 1.9 mg/kg compared to 0.4 mg/kg in pregnant rats. The ID50 ratio for diazepam in non-pregnant and pregnant rats was about 4.75. In both non-pregnant and pregnant rats, diazepam [1 mg/kg] markedly antagonized the uterotonic effects of oxytocin [1 IU/kg] and PGF2alfa was found to be greater on the muscles of pregnant rats. However, such antagonism did not result in complete loss of the uterotonic activity of oxytocin and PGF2alfa as their [after diazepam] on both frequency and amplitude of uterine contraction were still significantly higher than just before oxytocin and PDSGF2alfa [effect of diazepam alone]. The effect of diazepam was also examined in-vitro on isolated non-pregnant rat uterus. It was found that diazepam in concentrations ranging from 0.125-16 microg/ml produced significant concentration-dependent reduction in the height of contraction elicited by either acetylcholine [1 micro g/ml] or KCl [2.2 mg/ml]. The concentration of diazepam that produced 50% reduction of acetylcholine and KCl responses [IC50] were 1.8 microg/ml and 0.75 micro g/ml respectively. In the presence of flumazenil, diazepam produced nearly the same relaxant effect on acetylcholine-induced contraction with an IC50 value of 2 microg/ml which was not significantly different from that obtained in the absence of flumazenil [1.8 micro g/ml]. In KCl depolarized uterine horns, diazepam [2 micro g/ml] with rightward shift of the concentration response curve of CaCl2, indicating a Ca2+ antagonistic activity for diazepam. It could be concluded that pretreatment with diazepam during near term pregnancy may lead to serious complications during the process of labour-induction by oxytocin or PGF2alfa

pharmacological role of glibenclamide on skeletal muscles in experimental animals

The effect of glibenclamide was studied on isolated toad's rectus abdominals muscle as well as on the gastrocnemius sciatic nerve preparation of anaesthetized rats. Glibenclamide [10 uM/ml] produced significant protestation of acetylcholine-induced contraction of isolated toad's abdominals muscle with shift of the concentration response curve of acetylcholine to the left. Moreover, it augmented the potentiating effect induced by eostigmine. Investigating the effete of serum cholinesterase enzyme revealed that gilbenclamide has the ability to antagonize the inhibiotory effect induced by serum. The contractile response of the isolated rectus muscle to caffeine and low concentrations of KCI were potentiated significantly b glibenclamide [10uM/ml], with shift of the concentration response curves to the left. However, contractions induced by high concentrations of KCI were significantly reduced with shift of the curves to the right. In anaesthetized rats, glibenclamide [0.5 mg/kg] elicited significant increase in the contractile tension of the hastrocenmius-sciatic nerve preparation in response to direct and indirect electrical stimulation. However, the depressor responses of the muscle induced by the calcium antagonists, verapamil and trifluroperazine were augmented by glibenclamide, while the depressor responses produced by dantrolene and atracurium were antagonized. Conclusively, glibenclamide, has an effect on contraction of the skeletal muscles induced by various stimuli, post probably mediated through an effect on cholinesterase enzyme and calcium ions movement

Experimental and clinical study of the effects of flavoxate in comparison with propantheline

In the present study the pharmacological effects of both flavoxate hydrochloride and propantheline bromide were studied experimentally on urinary bladder strips, intestinal smooth muscles, hearts and aortic strips isolated from rabbits. In-vivo experiments were also carried out to detect their effects on mean arterial blood pressure, heart rate and intraocular pressure of anaesthetized rabbits. In addition, antisecretory effects on basal gastric secretion in rats were investigated. Finally, both drugs were evaluated urodynamically in a clinical study on patients with cystitis. Each of flavoxate and propantheline elicited a significant concentration dependent spasmolytic effect on isolated urinary bladder strips and jejunal smooth muscles. Flavoxate was found to be more selective than propantheline on urinary bladder smooth muscle with potency ratio equal to 38.2. On the other hand, propantheline was found to exhibit a higher selectivity on isolated intestinal smooth muscle with potency ratio equal to 82.2. Comparing the smooth muscle relaxant activity of flavoxate and propantheline on the previous tissues, it was found that flavoxate activity was 237.4 times higher at the urinary bladder while propantheline activity was 13.2 times higher at jejunal smooth muscle. Flavoxate and propantheline displaced the Ach concentration response curves of the rabbit urinary bladder strips to the right. Propantheline and flavoxate produced competitive and weak anticholinergic activities with percentages of antagonistic actions about 83.3% and 33.3% respectively. The Ca [++] antagonistic activity of flavoxate was confirmed in the performed study on CaCl[2] concentration response curves on isolated urinary bladder strips depolarized with KCl, flavoxate produced competitive antagonism with the percentage of 76.5% while propantheline elicited non competitive Ca [++] antagonism with the percentage of 8.8%. Flavoxate also expressed its Ca[++] antagonistic activity on isolated rabbit hearts and aortic strips. Furthermore, in water cystometric recordings for patients with cystitis, flavoxate was more effective in increasing bladder capacity indicating its effect on micturition center, while bladder contractility was decreased more by propantheline denoting its higher antimuscarinic activity