Antioxidant and immunostimulatory effect of statin, fenofiberate and triton in infection

Statins and fenofibrate are the most effective pharmacological agents used to treat hyperlipidemia. Better understanding of various pleotropic effects of statins and fenofibrate have prompted a new surge of interest in their use to treat or prevent a wide range of chronic and life-threatening disorders. Male Swiss albino mice were treated with either heat killed E. coli or saline. They were classified into 14 groups. The effects of simvastatin and fenofibrate ill with a low and a high triton dose [200 and 400 mg/kg /three times weekly for 3 weeks] on the levels of interferon-gamma [IFN-gamma], total immunoglobulins and total antioxidant activity were examined in both normal and immunized mice. Simvatatin and fenofibrate administration together with the low or high triton dose or triton alone, induced a significant rise in the level of interferon-gamma [IFN- gamma] and total immunoglobulins in immunized animals as compared to non-immunized ones. Moreover, there was all in the total antioxidant activity upon treatment with either simvastatin or fenofibrate in non-immunized and immunized hyperlipidemic mice. In conclusion, these findings revealed that treatment with low or high dose triton in combination with either simvastatin or fenofibrate increased the acquired immunity by increasing the level of interferon- gamma and total immunoglobulins. In addition, these combinations also increased the antioxidant activity during infection

Modification of the antinflammatory, antipyretic and analgesic effects of meloxicam with omeprazol or ranitidine in exeperimental animals

The potential modification of the anti-inflammatory, antipyretic and analgesic effects of meloxicam in concurrent administration of omeprazole or ranitidine was assessed. This study was divided into two sets of experiments. In the first set of experiments, male albino rats were divided into 2 main groups: Group I: to study the anti-inflammatory activity of the tested drugs by induction of inflammation by subcutaneous injection of 0.1mI of 20% brewer's yeast suspension into planter surface of the right hind paw and measuring the rats paw thickness according to the treatment received. Group II: to study the anti-pyretic activity of the tested drugs by induction of pyrexia by subcutaneous injection of 2. 5m1 of 20% aqueous suspension of yeast dorsally and ventrally and recording the rectal temperature according to the treatment received. In the second set of experiments, mice were divided into two main groups: Group I: The analgesic activity of the tested drugs was evaluated by chemical method [p-benzoquinon induced-writhing response]. Group II: The analgesic activity of the tested drugs was evaluated by thermal method [hot plate method]. Intraperitoneal [i.p.] administration of meloxicain produced a significant reduction in the rat paw edema [P<0. 05]. Combined i.p. injection of meloxicam and ranitidine caused a significant decrease in the rats paw edema [P<0. 05]. Also, the combined i.p injection of meloxicam and omeprazole caused a significant reduction in the rat's paw edema [P<0. 05]. Intraperitoneal administration of meloxicam into hyperthermic rats led to a remarkable reduction in body temperature of rats. Combined administration of meloxicam and ranitidine or meloxicam and omeprazole produced a significant decrease in the body temperature [P<0. 05]. The i.p administration of meloxicam before the injection of P-benzoquinon [PBQ] protected the animals against writhing response. The concurrent administration of meloxicam and ranitidine or meloxicam and omeprazole resulted in protection of animals from PBQ-induced writhing response which was significant [P<0. 05]. Furthermore, the combined administration of meloxicam and ranitidine or meloxicam and omeprazole caused a significant increase in the reaction time to thermal stimulus [P<0. 05]. On the other hand, i.p. injection of ranitidine or omeprazole alone caused non significant change in the rat's paw edema or yeast induced pyrexia, but ranitidine caused a significant decrease in PBQ-induced writhing response and in hot plate-induced pain [P<0.05]. In addition, omeprazol produced non significant change in PBQ-induced writhing response and in hot plate-induced pain. It could be suggested that in choice of the use of one of antiulcer drugs with meloxicam we prefer to use ranitidine over omeprazole as ranitidine potentiated the analgesic effect of meloxicam

effectiveness of beta adrenoceptor antagonists on progression of insulin resistance and type 2 diabetes in high fat diet-fed rats

The effects of carvedilol a third generation beta-blocker on progression of insulin resistance and type 2 diabetes mellitus were compared to the prototypic non-selective beta-blocker, propranolol. Male albino rats were fed a high fat diet [HFD] for 3 months to induce insulin resistance and mild type 2 diabetes [T2DM] Oral administration of carvedilol [2 or 20 mg/kg], propranolol [30 mg/kg], or vehicle was started along with HFD in different groups. Indices of body composition and insulin resistance, oral glucose tolerance, fasting serum insulin levels, lipid profile, serum levels of lipid peroxidation markers as well as levels of advanced glycosylation end products were determined. In high fat-fed animals, an increase in body composition index, area under the oral glucose tolerance curve, fasting serum insulin, and insulin resistance were observed in comparison to normal diet controls. In addition, significant dyslipidemic changes were also observed in these animals. Moreover, in concordance with these hyperglycemic and dyslipidemic changes, HFD significantly increased serum levels of markers of lipid peroxidation and advanced glycosylation end products [AGEs]. On the other hand, beta-adrenergic blockers treatment showed better effects on glucose disposal, insulin levels, and insulin resistance. However, carvedilol treatments showed enhanced lipid profiles and lower AGEs when compared to propranolol treatment in HFD animals. These preferential metabolic effects of carvedilol can be attributed to its antioxidant effects and negative regulation of lipolysis. We concluded that carvedilol have protective effects against the development of insulin resistance and T2DM, in addition to amelioration of the consequent cardiovascular complications

Modification of antiinflammatory, antipyretic and analgesic effects of celecoxib with some antiulcer drugs in experimental animals

Patients under antiulcer therapy may suffer from a concurrent disease which requires the use of one of NSAIDs, In such cases, these patients are likely to receive a combination of one of the antiulcer drugs plus the NSAIDs. Accordingly, the simultaneous use of one of the NSAIDs with one of the antiulcer drugs may lead to drug-drug interaction. The present work was devoted to the assessment of the modification of the anti-inflammatory, antipyretic and analgesic effects of celecoxib after the concurrent administration of the antiulcer drugs, omeprazole and ranitidine. This study was performed on two animal species, rats and mice. Rats were used to detect the anti-inflammatory and the antipyretic activities of the investigated drugs. Mice were utilized to study the analgesic activity of the same drugs.Male albino rats were divided into 2 main groups: Group I. rats were divided into 5 subgroups, to study the anti-inflammatory activity of the tested drugs by induction of inflammation by subcutaneous injection of 0.1 ml of 20% brewer's yeast suspension into planter surface of the right hid paw and measuring the rats paw thickness according to the treatment received. Group II: rats were divided into 5 subgroups, to study the anti-pyretic activity of the tested drugs by induction of pyrexia by subcutaneous injection of 2.5ml of 20% aqueous suspension of yeast dorsally and ventrally and recording the rectal temperature according to the treatment received. GroupIII: mice were divided into two set of experiment each of which divided into 5 subgroups. The analgesic activity of the drugs was evaluated by chemical method [p-benzoquinon induced -writhing response and the thermal method [hot plate method]. Intraperitoneal [i.p.] administration of celecoxib produced highly significant reduction in the rat's paw edema. Intraperitoneal injection of celecoxib and ranitidine caused highly significant decrease in the rat's paw edema. Similarly the combined i.p injection of celecoxib and omeprazole gave a highly significant reduction in the rat's paw edema. Intraperitoneal administration of celecoxib Into hyper-thermic rats led to a remarkable reduction in body temperature of rats. Combined administration of celecoxib and ranitidine produced highly significant decrease in body temperature. The combined i.p administration of celecoxib and omeprazole caused a highly significant decrease. In body temperature. The i.p administration of celecoxib before the injection of P-benzoquinon [PBQ] protected the animals against writhing response. Intraperitoneal injection of celecoxib and ranitidine resulted in protection of animals from PBQ-induced writhing response which was highly significant. The simultaneous administration of celecoxib and omeprazole protected the animals from PBQ-induced writhing response which was highly significant. Intraperitoneal injection of celecoxib revealed a highly significant increase in the reaction time. The combined administration of celecoxib and ranitidine caused highly significant increase in the reaction time. Intraperitoneal administration ofcelecoxib and omeprazole also produced highly significant increase in the reaction time to thermal stimulus. Intraperitoneal injection of ranitidine or omeprazole caused non significant change in the rat's paw edema or yeast induced pyrexia, but ranitidine caused a significant decrease in PBQ-induced writhing response and in hoi plate-induced pain. On the other hand omeprazol produced non significant change in PBQ-induced writhing response and in hot plate-induced pain. It could be suggested that ranitidine is a relatively better drug than omeprazole with respect to anti-inflammatory, antipyretic and analgesic actions when used concurrently with a selective COXII inhibitor

Influence of praziquantel on the levels of certain essential hepatic metabolizing enzymes in schistosoma mansoni infected mice

This study was carried out on mice infected with three different levels of Schistosoma mansoni [S. mansoni] cercariae as well as non infected mice for the assessment of the influence of praziquantel on the pattern of some members of essential hepatic metabolizing enzymes. The results showed a significant increase in the hepatic content of the microsomal protein, cytochrome P-450 [Cyt P450], cytochrome b5 [Cyt b5], hepatic glutathione [GSH] and the activity of glutathione-S- transferase [GST] in all infected mice. The magnitude of this increase was in direct relationship with the level of infection. Praziquantel failed to produce any significant effect in all tested hepatic components of the non-infected mice. However, its administration into the infected mice produced variable modulation on the hepatic components that were previously elevated during infection. The elevated levels of the hepatic microsomal protein, Cyt P450, Cyt b5 and activity retreated under the influence of praziquantel to approximate the normal [preinfection] levels

Comparison between the effects of early schistosoma mansoni infection and the classical inducers phenobarbitone and 3-methylcholanthrene on some hepatic microsomal monooxygenases

Hepatic schistosomiasis was induced experimentally in male albino mice using Schistosoma mansoni [S. Mansoni] cercariae for a period of 33-days post infection. Five different levels of infection [60, 120, 180, 300 and 600 cercariae/mouse] were used for the assessment of the comparison of their effects on some hepatic microsomal monooxygenases with those produced by classical enzyme inducers phenobarbitone [PB] and 3-methylcholanthrene [MC]. Similar to the two tested classical inducers, the 33 days post infection of mice with S. mansoni increased the total microsomal protein content [23.6%, 40.5%, 59.9%, 47.2% and 33.7%] and the specific concentration of cytochrome P450 Cyt P450 [26.8%, 35.4%, 71.7%, 56.7% and 48.0%] at all tested infection levels. The maximum increase was recorded at the infection level of 180 cercariae/mouse

Comparison between the effect of pyrazole, cobalt and tin on hepatic and renal microsomal cytochrome P450 concentration and metabolism of coumarin and 7 ethoxycoumarin

Recently, the metabolism of coumarin and 7-ethoxycoumarin were reported to be enhanced several folds in the mouse liver after pretreatment with either N-containing heteroaromatic compounds [e.g. pyrazole, PL] or heavy metals [e.g. Cobalt, Co and Tin, Sn]. The effect of these compounds on the mouse renal microsomes is not thoroughly investigated. Accordingly the present study was designed to compare the effect of pyrazole. cobalt and tin on hepatic and renal microsomes. The study revealed that in both kidney and liver microsomes, the concentration of Cyt P450 was decreased to about the same extent after pretreatment of male mice [NMRI-type] with these compounds. In contrary the metabolism of 7-ethoxy-coumarin and of Coumarin were increased several folds. In the liver microsomes, the highest increase in the metabolism of the coumarin derivatives, were observed after pretreatment of mice with Sn [Sn > PL > Co]. On the other hand, in the kidney microsomes, the most potent inducer was found to be PL [PL> Co>Sn]. These results indicate that PL, Co or Sn enhance the hepatic and renal metabolism of coumarin derivatives by different rates. Accordingly, these data suggested the different regulation of the coumarin derivatives metabolizing enzymes in the -liver from that in the kidney

Comparitive study of hepatic coumarin hydroxylase [cyp2a-5] induction by heavy metal tin

The selective induction of the hepatic coumarin hydroxylase [Cyp 2a-5] elicited by the heavy metal tin [Sn C12] has been compared in male NMRI mice with that of the standard inducers, phenobarbitone [PB] and 3-methylcholanthrene [MC]. Although the standard inducers, PB and MC increase the microsomal specific content of cytochrome P 450 [P 450/mg microsomal protein], stannous chloride leads to a decrease in this concentration. On the other hand, regarding Cyp 2a-5 activity, ethoxycoumarin O-deethylase was increased to about 3.5-fold and coumarin 7-hydroxylase as much as 8-fold after pretreatment with stannous chloride. This-increase was much higher than that caused by PB, the only well known inducer of coumarin 7-hydroxylase and MC. However, the 2.2- or 2.4-fold increase in the N-demethylation of ehtylmorphine of benzphetamine, the model substrate used to visualize the latent PB-induction, by PB were insignificantly decreased after pretreatment by stannous chloride. The same is true when ethoxyresorufin O-deethylation, which would indicate MC-induction type was considered. Stannous chloride did not affect such activity whereas the MC increases it to about 11-fold. The data indicate that the heavy metal salt-stannous chloride causes induction of microsomal monooxygenase complex selective for coumarin 7-hydroxylase and 7-ethoxycoumarin O-deethylase and does not affect the rate of metabolism of model substrates, which would indicate a PB-or MC-type of induction