ABSTRACT
Objective: To investigate the effect of Cannabis sativa extract on the development of neuro- and hepato-toxicity caused by malathion injection in rats. Methods: The extract of Cannabis sativa was obtained from the plant resin by chloroform treatment. Δ-Tetrahydrocannabinol content of the extract (20%) was quantified using gas chromatography-mass spectrometry. The doses of cannabis extract were expressed as Δ -tetrahydrocannabinol content of 10 or 20 mg/kg. Malathion (150 mg/kg) was intraperitoneally administered followed after 30 min by the cannabis extract (10 or 20 mg/kg, subcutaneously). Rats were euthanized 4 h later. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide and paraoxonase-1 (PON-1) activity were determined in brain and liver. Brain 5-lipoxygenase and butyrylcholinesterase (BChE) activity were measured as well. Histopathological examination of brain and liver tissue was also performed. Results: Compared to controls, malathion resulted in increased oxidative stress in brain and liver. MDA and nitric oxide concentrations were significantly increased (P<0.05) and GSH significantly decreased with respect to control levels (P<0.05). Malathion also significantly inhibited PON-1 and BChE activities but had no effect on brain 5-lipoxygenase. Brain MDA concentrations were not altered by cannabis treatment. Cannabis at 20 mg/kg, however, caused significant increase in nitric oxide and restored the GSH and PON-1 activity. Brain BChE activity significantly decreased by 26.1% (P<0.05) after treatment with 10 mg/kg cannabis. Cannabis showed no effect on brain 5-lipoxygenase. On the other hand, rats treated with cannabis exhibited significantly higher levels of liver MDA, nitric oxide and PON-1 activity compared with the malathion control group. Rats treated with only malathion exhibited spongiform changes, neuronal damage in the cerebral cortex and degeneration of some Purkinje cells in the cerebellum. There were also hepatic vacuolar degeneration and dilated and congested portal vein. These histopthological changes induced by malathion in brain and liver were reduced to great extent by cannabis administration at 20 mg/kg. Conclusions: Our data suggest that acute treatment with cannabis alleviates the malathion-induced brain and hepatic injury in rats possibly by maintaining the levels of GSH and PON-1 activity.
ABSTRACT
Cannabis sativa has long been known for its psychotropic effect. Only recently with the discovery of the cannabinoid receptors, their endogenous legends and the enzymes responsible for their synthesis and degradation, the role of this 'endocannabinoid system' in different pathophysiologic processes is beginning to be delineated. There is evidence that CB1 receptor stimulation with synthetic cannabinoids or Cannabis sativa extracts rich in Δ(9)-tetrahydrocannabinol inhibit gastric acid secretion in humans and experimental animals. This is specially seen when gastric acid secretion is stimulated by pentagastrin, carbachol or 2-deoxy-d-glucose. Cannabis and/or cannabinoids protect the gastric mucosa against noxious challenge with non-steroidal anti-inflammatory drugs, ethanol as well as against stress-induced mucosal damage. Cannabis/cannabinoids might protect the gastric mucosa by virtue of its antisecretory, antioxidant, anti-inflammatory, and vasodilator properties.
ABSTRACT
Cannabis sativa has long been known for its psychotropic effect. Only recently with the discovery of the cannabinoid receptors, their endogenous legends and the enzymes responsible for their synthesis and degradation, the role of this ‘endocannabinoid system’ in different pathophysiologic processes is beginning to be delineated. There is evidence that CB
ABSTRACT
The effect of Ginkgo biloba extract on acute liver injury caused by CCl4 was studied and compared to that of silymarin in the rat. Ginkgo biloba at doses of 25 or 50 mg/kg or silymarin at dose of 22 mg/kg was given once daily orally for 15 days starting at time of CCI[4] administration. Ginkgo biloba at 50 mg/kg conferred- significant protection against the hepatotoxic actions of CCl[4], reducing serum aspartate aminotransferase [AST], alanine aminotransferase [ALT] and alkaline phosphatase [ALP] levels to 39.6%, 46.8% and 33.1% of that of controls, respectively. In comparison, the elevated serum AST, ALT and ALP levels decreased to 28.4%, 45.1% and 34.2% of controls, respectively by 22 mg kg of silymarin. Histological examination showed marked decrease in centrilobular necrotic areas in rats treated with silymarin or ginkgo biloba. Rats treated with ginkgo biloba revealed more or less normal hepatocyte architecture. Stained sections were subjected to morphometric evaluation using computerized image analyzer. On image analysis, the area of damage was reduced by 34.8%, 65.5% by 25 or 50 mg/kg ginkgo biloba and by 89.2% by 22 mg/kg silymarin, respectively. The study suggests that administration of ginkgo biloba in a model of CCl4 induced liver injury result in less liver damage. Ginkgo biloba might be of value in the therapy of chronic hepatitis
ABSTRACT
vinpocetine is a widely used drug for the treatment of cerebrovascular and memory disorders. This study aimed to investigate the effect of vinpocetinc on the acute hepatic injury caused in the rat by the administration of CCl[4] in viva. Vinpocetine [2.1, 4.2, 8.4 mg/kg] or silymarin [30 mg/kg] was given once daily orally simultaneously with CCl[4] and for 15 days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. Stained sections were subjected to morphometric evaluation using computerized image analyzer. The results showed that vinpocetine administered to CCl[4]-treated rats decreased the elevated alanine aminotransferase [ALT] by 49.3, 58.] and 63.6%, aspartate aminotransferase [AST] by 10.5, 22.6 and 27.2% and alkaline phosphatase [ALP] by 52.5, 59.6 and 64.9%, respectively and in a dose-dependent manner. Meanwhile, silymarin reduced elevated ALT, AST and ALP levels by 53.1, 26.9 and 66%, respectively. Histological examination of liver specimens revealed a marked reduction in liver cell necrosis in vinpocetine and silymarin- treated rats compared with vehicle-treated CCl[4]-treated rats. Quantitative analysis of the area of damage showed 85.3% reduction in the area of damage after silymarin and 72.2, 78.9 and 85.3% reduction after vinpocetine treatment at 2.1, 4.2, 8.4 mg/kg, respectively. It is concluded that administration of vinpocetine in a model of CCl4-induced liver injury in rats resulted in reduction of liver damage. The reduction obtained by 4.2 mg/kg of vinpocetine was similar to that obtained by 30 mg/kg silymarin. Therefore, it is suggested that vinpocetine might be a good pharmacological agent in the treatment of liver disease besides its neuroprotective effects
ABSTRACT
In this study, we investigated whether alpha2-adrenoceptors are involved in the antinociception induced by different classes of antidepressant drugs using the acetic acid-induced writhing test in mice. The subcutaneous [s.c.] administration of the non-selective noradrenaline and serotonin rcuptake inhibitors; imipramine and amitriptyline; the selective 5-hydroxytryptamine [serotonin] reuptake inhibitors [SSRJs]; fluoxetine and sertraline and the heterocyclic agent; trazodonc caused dose-related decrease in the number of abdominal constrictions [writhings] caused by intraperitoneal [i.p.] injection of dilute acetic acid in mice. The acute analgesia induced by amitriptyline, sertraline and trazodone was blocked by co-administration of the alpha2-adrenoceptor antagonist yohirnbine [4 or 8 mg/kg]. In contrast, alpha-2 blockade enhanced imipramine-induced an1inociception. Meanwhile, yohimbine administration at 4 mg/kg bu1 not 8 mg/kg significantly reduced the fluoxetine-induced analgesia. These data suggest that alpha2-adrenoceptors mediate the analgesic effect of some antidepressant drugs independent of their effect on neurotransmitter release. The present data also suggest that distinct routes mediate the analgesic effect of individual agents within the same class of antidepressant drugs
ABSTRACT
The effect of the non-selective cyclo-oxygenase inhibitors indomethacin. Diclofenac, sulindac, tolmetin, piroxicam and the selective cyclo-oxygenase type 2 [COX-2] inhibitors celecoxib and rofecoxib on biliary secretion was studied in urethane anaesthetised rats. Drugs were intraperitonealIy administered prior to bile duct cannulation and bile collection. Bile secretions were collected at 30-min intervals for 4 h following drug administration. Bile flow was determined. In addition, total proteins, cholesterol, total, lipids, glucose and several hepatic enzymes were assessed in bile. Results indicated that basal bile secretion was unchanged after diclofenac, but decreased after piroxicam, indomethacin, tolmetin, celecoxib and rotecoxib administration by 23-25%. In contrast, bile flow was increased by 39.3-66.6% after the administration of sulindac. The concentration of cholesterol in bile was increased by all NSAIDs examined. Cholesterol secretion into bile was increased by indomethacin, Piroxicam, high dose sulindac, celecoxib and rofecoxib. All NSAIDs in the study decreased lipid secretion into bile to variable extent. Protein secretion was unchanged by most drugs, but increased by diclofenac and small dose rofecoxib and decreased by tolmetin. These data collectively suggest that NSAIDs alter biliary secretion and composition which is likely to have important clinical implications. Data also suggest that preferential COX-2 inhibition did not result in marked difference compared with conventional NSAIDs as regards the effect on bile flow, cholesterol or biliary lipid secretion
ABSTRACT
This study aimed to investigate the hepatoprotective effect of the bile salt taurine and its interaction with silymarin or melatonin on the acute hepatic injury caused in the rat by the administration of acetaminophen in vim. Taurine [50. 100 or 200 mg/kg] or taurine [100 mg/kg] combined with either siLymarin [22 mg/kg] or melatonin [3 mg/kg] was given orally twice daily for 7 days, starting on time of acetaminophen administration. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. Taurine exerted dose-dependent protective effect reducing serum levels of hepatocellular enzymes. When administered at a dose of 50 mg/kg, taurine significantly reduced plasma ALT value by 35.3%. At doses of 100 and 200 mg/kg, the drug caused significant reduction in plasma ALT [by 43.6 and 51.8%], AST [by 16 and 32.4%] and ALP [by 22.6 and 26.2%]. Silymarin [22 mg/kg] co-administrated with taurine [100 mg/kg] resulted in further decrease in plasma AST, whereas the combination of taurine 100 mg/kg and melatonin [3 mg/kg] exhibited significantly lower plasma ALT and AST levels compared with those given 100 mg/kg taurine alone. Examination of liver specimens revealed a marked reduction in liver cell necrosis in taurine-pretreated rats compared with the control acetaminophen-treated rats. The addition of either melatonin or silymarin resulted in further histological improvement. The present study thus indicates that in the model of acetaminophen-induced hepatic toxicity. taurine was useful in decreasing hepatic damage and the combination of taurine and melatonin or taurine and silymarin proved more effective
ABSTRACT
Gastric antral biopsies were obtained from 40 insulin-dependent diabetics [IDDM] and non-insulin dependent diabetics [NIDDD] in Kasr El-Aini Hospital [13 males and 27 females]. Endoscopy showed that 47.5% of the patients have normal endoscopic appearance. Antral gastritis was present in 47.5%, esophagitis in 15% and duodenitis in 12.5% of patients. Campylobacter pylori were isolated from the antral mucosa of 22.5% of the patients. 15.8% of these patients have normal endoscopic findings, 31.6% of patients have gastritis. No Campylobacter pylori were isolated from biopsies obtained from patients having only duodenitis. No significant difference in prevalence of Campylobacter pylori was found between the two groups of diabetes. Candida albicans were isolated more frequently from antral gastric biopsies than Campylobacter pylori