possible antidiabetic role of selective beta-3 adrenoceptor agonist in animal models of diabetes mellitus

Control of blood glucose is a key objective in the management of type I and type II diabetes mellitus [DM] as well. The basis for development of new antidiabetic drug is the proper control of the hyperglycemia and furthermore could manage accompanying [isomers especially dyslipidemia. The aim of this study was to investigate a newly developed Beta-3 adrenergic agonist [BRL 37344] to confirm its effect on blood glucose in two animal models of DM. which induced by streptozotocin [STZ] in a dose of 70 or 40 mg/kg for induction of type I or II D. M, respectively and try to explore for the possible underlying mechanism this effect. Oral administration of BRL 37344 for 4 successive days in either STZ type I or STZ type II diabetic rats produced significant reduction in mean serum glucose level and non-significant change in mean serum insulin level in comparison with non treated STZ diabetic rats. BRL treatment significantly increased glucokinase activity and decreased glucose-6-phosphatase activity in hemogenated hepatic tissues which were isolated from both STZ diabetic rat models. In in-vitro study, BRL. produced non-signiticant changes in insulin secretion from isolated pancreatic tissue of STZ type II diabetic rats, while BRL showed significant increase in glucose uptake by isolated soleus muscle from both STZ diabetic rat models. These results showed that selective stimulation of the [Beta-3 -adrenoceptors in diabetic rats, produced significant antihyperglycemic effect. This effect is not through stimulation of pancreatic insulin secretion but it is through inhibition of hepatic glucose output or enhanced glucose utilization by skeletal muscles

Effect of non steroidal anti-inflammatory drugs on the diuretic effect of bumetanide in rats

This study was designed to explore the possibility of interaction between non-steroidal anti-inflammatory drugs [NSAIDs] and loop diuretics [bumetanide] using selective cyclooxygenase-2 [COX-2] inhibitor [meloxicam] and non- selective cyclooxygenase inhibitor [indomethacin]. Animals were divided into six groups, each contained 16 rats. Four rats of each group were caged in a metabolic cage designed for urine collection. The results of this study were presented and discussed

Effect of angiotensin converting enzyme inhibitors on gentamicin nephrotoxicity in rats

The effect of two angiotensin converting enzyme inhibitors; namely, captopril [1.8 mg/kg/day orally] and enalapril [0.8 mg/kg/day orally] on gentamicin induced nephrotoxicity [each given seven days pretreatment for 14 days concomitantly with gentamicin] was studied in rats. Treatment with gentamicin [40 mg/kg/day IP for 14 days] resulted in an increased serum malondialdehyde and a significant decrease of urinary prostaglandin E2. It could be concluded that angiotensin converting enzyme inhibitors were of a significant value in the protection against nephrotoxic insults and they are worth to be tried clinically

Effect of silymarin on some nephrotoxic drugs in rats

The aim of this study was to examine whether silymarin could protect against renal injury due to the nephrotoxic drugs as gentamicin and cisplatin. Animals were subdivided into six groups, each containing ten rats: The first group was used as a control and received normal saline orally at a dose of 0.5 ml/day for seven days, the second group was treated with silymarin orally at a dose of 200 mg/kg/day for seven days, the third group was treated with gentamicin at a dose of 80 mg/kg/day IP for seven days, the fourth group was treated with cisplatin at a single dose of 5 mg/kg IV infusion and the fifth and sixth groups were pretreated with silymarin for seven days. The present data showed clearly the protective effect of silymarin against experimentally induced nephrotoxicity

Evaluation of the possibility of prophylactic and therapeutic effects of praziquantel in adjuvant arthritic rats

This work was designed to study the effect of praziquantel [an antibilharzial drug] on adjuvant arthritis in rats in comparison with indomethacin. An animal model of adjuvant arthritis was adopted in rats by intradermal injection of Freund's adjuvant. Oral administration of praziquantel in adjuvant arthritic rats at a dose of 187 mg/kg/week for four weeks as a prophylactic or therapeutic regimen resulted in a significant anti-inflammatory effect which was more or less similar to indomethacin. It was concluded that the administration of praziquantel could be used for the treatment of rheumatic diseases and it could prevent the progress of the rheumatic disease

Evaluation of the diuretic effect of natural honey in rats

The aim of this study was to evaluate the possibility of a diuretic effect of natural honey in rats and the possible mechanism of action. Oral administration of honey to rats at a dose of 1, 2, 4 or 8 gm/kg resulted in a diuretic effect as compared with the control group. In comparison with hydrochlorothiazide, there was no significant difference between honey and hydrochlorothiazide as regards urine volume, but the diuretic effect of honey was accompanied with a more significant increase in sodium and chloride excretion when compared with the effect of hydrochlorothiazide. The results showed that diuretic effect of honey was not attributed to the osmotic effect of its sugar content, since a mixture of glucose-fructose-sucrose and maltose [GFSM] in the same proportions as they were found in natural honey given to rats orally at a dose of 4 gm/kg and 8 gm/kg did not produce any diuretic effect

Prophylactic effect of Nigella sativa on hepatic injury in rats

Thirty albino rats were used for investigation of the effect of Nigella sativa on paracetamol induced hepatic necrosis. The rats were divided into 3 equal groups. Nigella sativa protected rats against paracetamol and carbon tetrachloride hepatic injury evidenced by improvement of the histopathological changes and normalization of the biochemical changes induced by either paracetamol or CCL4

effects of melatonin administration on some endocrine functions in rats

This study was conducted to investigate the effects of chronic oral melatonin administration in dose of 0.4 mg/kg B.W. daily for 30 days on serum TSH, T4, FSH, LH and insulin. 160 albino rats of both sexes were used, they were grouped into 16 groups, of which 8 groups were used to investigate the endocrinal effects of melatonin in both light and dark conditions. The other 8 groups were used for the same investigations under stressful condition in both light and dark as well. Half of all these groups were served as placebo controls. It was concluded that exogenous melatonin is recommended only as replacement therapy for persons sleeping in light to avoid disturbance of thyroid function especially in hyperthyroid patients. Also, melatonin has no role in counteracting the effects of acute stress on the endocrine functions related to TSH, T4, LH, FSH and insulin

Comparative study of non-steroidal anti-inflammatory drugs [NSAIDs] and their interaction with drugs affecting prostaglandins

This experimental study was carried out to evaluate the possible therapeutic and toxic effects of a more or less recent non-steroidal anti-inflammatory drug [NSAID], tenoxicam, in management of rheumatoid arthritis model in rats in comparison with indomethacin, being a standard one and piroxicam as a member of its group [oxicams]. In addition, a possible interaction between tenoxicam and both the anti- hypertensive drugs, captopril and clonidine, was also studied. This study was carried out in rats in which rheumatoid like-arthritis was induced experimentally by collagen II and complete Freund's adjuvant mixture

Preliminary study of the anti diabetic effect of sammo in rats

The dried powdered leaves of sammo plant has been used for a long time by some diabetic patients in the sense that it improved their diabetic state In our study, we tested the effect of the leaves of sammo on the blood glucose level, serum bilirubin, serum oxalecetic transaninase [SGOT], serum pyrvic transaminase [SGPT], serum bilirulin and serum ceratinine in non diabetic and alloxanized diabetic rats. Also histopathologicl examination of the pancreas [using modified aldehyde fuchsin stain], liver and kidney [using Hematoxlin and Eosin stain] was performed. Administration of the dried powder leaves of sammo orally, to non diabetic and diabetic rats in a dose of 1.2 gram/kg/day for 30 days produced significant decrease of the fasting serum glucose when the serum glucose was estimated 15 days and 30 days after administration of the dried powdered leaves of sammo Histopathological examination of the pancreas [using modified aldehyde fuchsin stain] of diabetic rats revealed that the dried powdered leaves produced regeneration of the beta cells of the islets of longerhans similarly hyperplasia of beta cells of the islets of langerhans was demonstrated in the non diabetic rats after administration of the dried powdered leaves of the plant. No toxic effect on the liver or kidney was evidence in non diabetic or diabetic rats after oral administration of the dried powdered leaves of the plant 30 days to non diabetic and diabetic rats, evidence by biochemical and histopathological study. Further investigations, including long term toxicity studies are necessary before it is justifiable to use the dried powdered leaves of the plant by the diabetic patiens

Importance of time of administration of levamisole in adjuvant arthritic rats

The effect of oral levamisole on arthritis was studied in rats rendered arthritic by intradermal injection of Freund's adjuvant. In the arthritic rats, levamisole was given in a dose of 10 mg/kg/day for 7 days before injection of Freund adjuvant then Freund adjuvant was injected intradermally and levamisole was given daily from the first day of Freund adjuvant inoculation till the full development of arthritis [i.e.21days] as prophylactic agent or given after establishment of arthritis for 21 days as curative agent. It was found that the prophylactic administration of levamisole significantly decreased the arthritic disease activity as evidenced by increase pain threshold and reduction of development of paw oedema. On the other hand, administration of levamisole as therapeutic agent did not affect arthritic disease activity as evidence by its insignificant effect on pain threshold or paw oedema.The present findings strongly suggest the prophylactic, rather than the therapeutic value of oral levamisole in induced arthritis in rats and this should be taken in consideration for further clinical studies

Effect on interaction between clonidine and calcium channel blockers on vascular smooth muscles

The 2 alpha receptor triggered vasoconstriction appears to be largely dependent upon the influx of extracellular calcium ions. This study was conducted to study the interaction between calcium channel blockers [nifedipine and isradipine] and clonidine.Mongrel dogs were used to study this interaction on the blood pressure nifedipine and isradipine attenuated the effect of clonidine on the blood pressure. When dogs were subjected to bleeding, it was found that nifedipine and isradipine also attenuated the effect of clonidine on the blood pressure of dogs.Using Abino rat hind quarter preparations, it was found that nifedipine and isradipine produced significant increase in the vascular outflow rate. The effect of isradipine was more significant than that of nifedipine. Clonidine non- significantly decreased the vascular outflow rate nifedipine and isradipine significantly attenuated the vasoconstrictor response to clonidine and this should be taken in consideration if a subject under nifedipine or isradipine treatment needs alpha 2-stimulants for treatment of emergency hypotensive states

Effect of captopril on some hydroclorothiazide adverse metabolic effects in rats

This study was conducted to declare the effect of calcium channel blockers [nifedipine and isradipine] on the vasoconstrictor responseophenylephrine and norepinephrine.Mongrel dogs were used to study this interaction on the blood pressure, nifedipine and isradipine attenuated the effect of vasopressors on the blood pressure. The degree of attenuation was in the following order: norepinephrine > phenylephrine. When dogs were subjected to bleeding, it was found that nifedipine and isradipine also attenuated the effect of vasopressors on the blood pressure of dogs. The degree of attenuation was in the following order: norepinephrine > phenylephrine. Using Albino rat hind quarter preparations, it was found that nifedipine and isradipine produced significant increase in the vascular outflow rate. The effect of isradipine was more significant than that of nifedipine. Phenyleprine and norepinephrine significantly decreased the vascular outflow rate. Nifedipine and isradipine did not attenuate the vasoconstrictor response of phenylephrine and non significant attenuation to the vasoconstrictor response of norepinephrine was observed. In conclusion, and 2 -mediated vasoconstriction is mostly dependent upon the influx of calcium through calcium channels. This effect is almost totally blocked by nifedipine and isradipine. and1 -mediated vasoconstriction is mediated, by the previously mentioned mechanism and other mechanisms e.g. intracellular release of calcium. The vasopressor effect mediated by and 1-stimulant is resistant to total blockade by nifedipine or isradipine. Blockade of the vasoconstrictor effect mediated by and 1 or and 2 stimulants should be taken in consideration if a subject under nifedipine or isradipine treatment needs and 1 or and 2 stimulant for treatment of emergency hypotensive states

Effect of interaction between clonidine and tiaprofenic acid in experimental animals

The present work was done to study the interaction between clonidine. an antihypertensive drug which has a prostaglandin synthesis stimulating effect and tiaprofenic acid an analgesic anti-inflammatory drug which has prostaglandin synthesis inhibiting effect.It was found that tiaprofenic acid significantly decreased the hypotensive effect of clonidine in dogs.On the other hand, it was found that clonidine decreased the analgesic and anti-inflammatory effects of tiaprofenic acid significantly in arthritic rats, when the analgesemeter and rats paw edema meter were used for assessment of the analgesic and anti inflammatory effect. Accordingly, simultaneous administration of tiaprofenic acid and clonidine is not recommended because each drug may antagonise some beneficial effects of the other drug