role of quercetin in cisplatin-induced nephrotoxicity and hepatotoxicity in rats

This work was carried out to investigate the effect of quercetin on cisplatin [CDDP] induced nephrotoxicity and hepatotoxicity in male albino rats. Forty eight animals were divided equally into 6 groups. Group I served as control and was injected intraperitoneally with a single dose of 1 ml saline. Group II was treated with cisplatin in a single dose of 5 mg /kg i.p. Group III was used as control and was treated by oral ingestion of 1 ml gum acacia [5%] daily for 7 days.Group IV was treated by ingestion of quercetin dissolved in gum acacia in a dose of 50 mg /kg /day for 7 days .Group V was given quercetin, 50 mg / kg /day for 7 days followed by cisplatin in a single dose of 5 mg / kg .Group VI was injected with single cisplatin dose [5 mg / kg] after which quercetin was given orally, 50 mg /kg /day for 7 days. The nephrotoxic and hepatotoxic effects of cisplatin as well as its modification by quercetin were assessed either by biochemical or histopathological studies. Biochemical methods included measurements of urinary activity of N -acetyl - beta -glucosaminidase [NAG]; serum creatinine, urea as well as albumin. Glutathione [GSH] was measured in liver and kidney homogcnates while lipid peroxidation [Thiobarbituric acid reactive substance [TEARS] and nitric oxide [NO]] was measured in both serum and homogenates of the liver and kidney. Histopathological studies were performed using light and electron microscopic techniques as well as alkaline phosphatase in the brush border of the proximal and distal renal tubules. A single dose of cisplatin [5 mg/Kg i.p] produced a significant elevation in serum urea and creatinne, a decrease in serum albumin and marked increase of urinary NAG. Renal and hepatic toxicity was also confirmed by a significant decrease of glutathione in kidney and liver homogenates and a significant increase of serum and tissue Lipid peroxide and nitric oxide [NO]. Histopathological changes of the kidney show evidence of destruction mainly involving the proximal convoluted tubules and manifested by weak alkaline phosphatase reaction. Ultrastructurally, there was disruption of apical microvilli, swelling and vacuolation of mitochondria and many lysosomes. Cisplatin induced hepatotoxicity evidenced by mitochonehial injury and hepatocytes damage. Administration of querectin [50mg/kg] 7 days before and after cisplatin injection produced significant protection against nephrotoxicity and hepatotoxicity induced by cisplatin. The amelioration of nephrotoxicity and hepatotoxicity was evidenced by significant reduction in serum urea and creatinine concentration. In addition quercetin tended to normalize the decreased levels of serum albumin and the increased levels of urinary NAG. Quercetin prevented the rise of NO and lipid peroxides in plasma and in kidney and liver tissue homogenates and also prevented the reduction of kidney and liver GSH Histopathologically kidney cells and hepatocytes nearly returned to normal. Enzymes such as alkaline phosphatase in the brush border of the proximal tubular cells also returned to normal. These results suggest that quercetin has a protective effect on nephrotoxicity and hepatotoxicity induced by cisplatin

investigation of the possible mechanism for propranolol induced sexual dysfunction

Propranolol as a beta adrenergic blocking agent is widely used in therapeutics for many indications. The drug has been observed to produce sexual dysfunction in many patients. However, the mechanisms of this effect is still unclarified. The present work is designed to investigate the effect of subchronic administration of propranolol on rat testicular tissues and serum testosterone level. Propranolol was given in 3-dose levels for 4 weeks. Results revealed that propranolol could produce degenerative changes in the interstitial cells of Leydig as well as the sperm cells and this associated with significant reduction in serum testosterone level. These changes may be the cause of sexual dysfunction that complicate propranolol therapy. The possible mechanisms underlying these changes were discussed

comparison between the effect of calcium channel blocking agents and salbutamol on pregnant rabbit with reference to antagonism with oxytocin and prostaglandin F2a

The effect of Ca[2+] channels blocking agents verapamil and diltiazem either alone or in combination with oxytocin or prostaglandin F[2] alpha on pregnant rabbit's uterus near full term was studied in vivo. Verapamil [0. 25 mg/kg] produced significant decrease in the amplitude while diltiazem [0.5 mg/kg] produced significant decrease in both the amplitude and frequency of the uterine contractions with no effect on mean blood pressure. When the doses were doubled, both verapamil and diltiazem produced signficiant decrease in the amplitude and frequency of uterine contractions as well as significant decrease in the mean blood pressure. Although qualitatively similar results were obtained for salbutamol, the effects of the three drugs are different quantitatively. Their effects can be arranged in a decreasing order to be diltiazem > verapamil > salbutamol on the uterus and salbutamol > verapamil > diltiazem on systemic BP. In another set of experiments, verapamil [0.5 mg/kg] and diltiazem [1 mg/kg] were administered 5 minutes either before or after oxytocin as well as prostaglandins. Diltiazem completely abolished both oxytocin and prostaglandin F[2] alpha induced uterine activities while verapamil only partially did so. It can be concluded that Ca[2+] channel blockers can decrease the uterine activities and this effect can be used therapeutically to delay premature labour

Anti-inflammatory, antipyretic and analgesic actions of tramadol in combination with ketoprofen

The aim of this work is to study the anti-inflammatory, antipyretic and analgestic activity of tramadol in animals, and evaluating these activities when combined with ketoprofen, moreover, the local anaesthetic effect of tramadol was assessed. Tramadol 4.5 mg/kg was found to be devoide of anti-inflammatory activity against edematous paws rat induced by yeast injection. While in a dose of 9 mg/kg - produced significant anti-inflammatory activity in the same test. Furthermore, tramadol 9 mg/kg exerts antipyretic effects in experimentally hyperthermic rats, but in a dose of 4.5 mg/kg did not affect the body tempreture in the same test. When tramadol 4.5 mg/kg was given in combination with ketoprofen 4.5 mg/kg produced marked and highly significant anti-inflammatory and antipyretic effect. On the otherhand tramadol at the dose levels of 6.5 and 13 mg/kg in mice produced significant increase in the hot plate [HP] latency. In the combined experiments, 6.5 mg/kg for mice given concomitently with 6.5 mg/kg ketoprofen produced marked and significant prolongation in the HP latency. The combination of tramadol and ketoprofen produced better anti-infammatory, antipyretic and analgesic effect. Also the results indicate that - tramadol has a local anaesthetic effect

Cardiovascular and intestinal responses to melatonin administration

The effects of melatonin on both cardiovascular system and intestinal tract were investigated. The cardiovascular response was studied either in vitro using rabbit's isolated and perfused heart or in vitro. The intestinal effects of melatonin were investigated on isolated rabbits duodenum. It was observed that melatonin has cardiac and intestinal inhibitory effects. Trying to spot the site of such melatonin effects different drugs were used in combination with melatonin. It can be suggested that both serotonin receptors as well as calcium channels are involved as sites of melatonin action