Endothelium-dependent effect of sesame seed feeding on vascular reactivity of streptozotocin-diabetic rats: underlying mechanisms

Cardiovascular disorders continue to constitute major causes of morbidity and mortality in diabetic patients. In this study, the effect of chronic administration of sesame [Sesamum indicum L] seed feeding was studied on aortic reactivity of streptozotocin [STZ]-diabetic rats. Male diabetic rats received sesame seed-mixed food at weight ratios of 3% and 6% for 7 weeks, one week after diabetes induction. Contractile responses to KCl and phenylephrine [PE] and relaxation response to acetylcholine [ACh] and sodium nitroprusside [SNP] were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to PE was significantly lower in sesame-treated diabetic rats [at a ratio of 6%] relative to untreated diabetics and endothelium removal abolished this difference. Endothelium-dependent relaxation to ACh was also significantly higher in sesame-treated diabetic rats [at a ratio of 6%] as compared to diabetic rats and pretreatment of rings with nitric oxide synthase inhibitor, N[G]-nitro-l-arginine methyl ester [L-NAME] significantly attenuated the observed response. Two-month diabetes also resulted in an elevation of malondialdehyde [MDA] and decreased superoxide dismutase [SOD] activity and sesame treatment significantly reversed the increased MDA content and restored activity of SOD. We thus conclude that chronic treatment of diabetic rats with sesame seed could in a dose- manner prevent some abnormal changes in vascular reactivity through nitric oxide and via attenuation of oxidative stress in aortic tissue and endothelium integrity is necessary for this beneficial effect

Antinociceptive effect of curcumin, an effective constituent of turmeric, in diabetic rats and evaluation of the involvement of lipid peroxidation

This study was designed to investigate the antinociceptive effect of curcumin in diabetic rats by using the formalin and hot tail immersion tests. Wistar rats were divided into the following six groups: control; curcumin-treated control [50 mg/kg]; diabetic; sodium salicylate [SS]-treated diabetic; and two curcumin-treated diabetic groups [10 and 50 mg/kg]. Curcumin was administered seven days after streptozotocin injection for a total of five weeks. High-dose curcumin treatment of diabetic rats reduced the pain score in both acute and chronic phases of the formalin test [p<0.05]. SS-treated diabetic rats had a reduction in pain score only in the chronic phase of the formalin test [p<0.05]. In the hot tail immersion test, diabetic rats showed a significant reduction in tail flick latency compared to the control group [p<0.01]. High-dose curcumin treated diabetic rats showed significantly increased latency relative to untreated diabetic rats [p<0.05]. Diabetic rats also showed a significant increase in the tissue level of malondialdehyde [MDA; p<0.01]. High-dose curcumin treated diabetic rats had a significantly reduced level of MDA [p<0.05]. Chronic administration of curcumin could attenuate the nociceptive score in both the acute and chronic phases of the formalin test in a streptozotocin-induced experimental model of diabetes mellitus and increase thermal pain threshold. The beneficial effect of curcumin is partly attributed to attenuation of lipid peroxidation in the periphery

Chronic oral epigallocatechin-gallate alleviates streptozotocin-induced diabetic neuropathic hyperalgesia in rat: involvement of oxidative stress

Due to the anti-diabetic and antioxidant activity of green tea epigallocatechin-gallate [EGCG], this research study was conducted to evaluate, for the first time, the efficacy of chronic treatment of EGCG on alleviation of hyperalgesia in streptozotocin-diabetic [STZ-diabetic] rats. Male Wistar rats were divided into control, diabetic, EGCG-treated-control and diabetic and sodium salicylate [SS]-treated control and diabetic groups. For induction of diabetes, STZ was intraperitoneally injected [IP] at a single dose of 60 mg/Kg. EGCG was orally administered daily at doses of 20 and 40 mg/Kg for seven weeks; one week after diabetes induction. Finally, hyperalgesia was assessed using standard formalin, hot tail immersion and paw pressure tests. Meanwhile, markers of oxidative stress in brain were measured. Diabetic rats showed a marked chemical, thermal and paw pressure hyperalgesia, indicating that the development of diabetic neuropathy and EGCG treatment at a dose 40 mg/Kg significantly ameliorated the alteration in hyperalgesia [p < 0.05] in diabetic rats as compared with untreated diabetics. EGCG treatment [40 mg/Kg] also significantly decreased diabetes-induced thiobarbituric acid reactive substances formation [p < 0.05] and nitrite [p < 0.05] content and reversed the reduction of antioxidant defensive enzyme superoxide dismutase [p < 0.05]. The results may suggest therapeutic potential of EGCG for the treatment of diabetic hyperalgesia through the attenuation of oxidative stress

[ effect of thymoquinone on short-term spatial memory, passive avoidance learning and memory of diabetic rats and the involvement of hippocampal oxidative stress]

Chronic diabetes mellitus accompanies disturbance in learning, memory, and cognitive skills. With regard to anti-diabetic and antioxidant activity of thymoquinone [TQ], the effect of its chronic administration on learning and memory of diabetic rats was investigated. In this experimental study, male rats were divided into control, high dose TQ-treated control, diabetic, and low and high dose TQ- treated diabetic groups. TQ was administered i.p. at doses of 2.5 and 5 mg/kg one week after diabetes induction by streptozotocin, for 5 weeks. For evaluation of learning and memory, initial [IL] and step-through latencies [STL] were determined at the end of the study using passive avoidance test, and alternation behavior percentage was obtained using Y maze. In addition, hippocampal homogenate malondialdehyde [MDA] level was measured. STL significantly decreased in diabetic [p<0.01] and TQ-treated diabetic groups [p<0.001]; TQ treatment did not improve it in any of its doses. Alternation percentage was significantly lower in the diabetic group compared to the control [p<0.005]. TQ-treated diabetic group [at a dose of 5 mg/kg] showed a significantly higher score compared with diabetic group [p<0.01]. Diabetic rats also showed a significant increase in tissue level of malondialdehyde [p<0.01] and TQ treatment significantly reduced the level of MDA [p<0.05]. Although chronic treatment of diabetic rats with TQ could not enhance the capability of consolidation and recall in diabetic rats, it could improve spatial memory in them; part of its effect is via attenuation of lipid peroxidation

[ effect of curcumin on serum level of aspartate and alanine amoinotransferase and cardiac level of oxidative stress markers in diabetic rats]

Diabetes mellitus in long term accompanies with enhanced oxidative stress and decreased activity of antioxidant defense system. Due to antidiabetic and antioxidant activity of effective constituent of turmeric, curcumin, the effect of this component on serum level of aspartate and alanine aminotransferase and cardiac level of some oxidative stress markers were determined. In this experimental study, rats were divided into 5 groups, i.e. control, curcumin-treated control [50 mg/kg], diabetic, and curcumin-treated diabetic groups [10 and 50 mg/kg]. Curcumin was administered 7 days after streptozotocin injection for 5 weeks. Serum level of aspartate and alanine aminotransferase and heart tissue level of malondialdehyde [MDA] and nitrite and activity of Superoxide dismutase [SOD] were measured. Diabetic rats showed a significant increase in serum level of aspartate and alanine aminotransferase [p<0.01-0.05], while high-dose curcumin significantly reduced serum level of these enzymes [p<0.05]. In addition, diabetes was followed by increased level of MDA and nitrite in heart tissue [p<0.05-0.01] and non-significant decrease of SOD activity, whlie high-dose curcumin treatment significantly reduced MDA and nitrite level [p<0.05] and did not significantly change activity of SOD. Chronic treatment with curcumin could improve serum level of alanine and aspartate aminotransferase and some oxidative stress markers in cardiac tissue of diabetic rats

Varenicline ameliorates learning and memory deficits in amyloid beta[25-35] rat model of Alzheimer's Disease

Alzheimer's disease [AD] is a enfeeble neurodegenerative disorder characterized by increased beta-amyloid [Abeta] deposition and neuronal dysfunction leading to impaired learning and recall. Among proposed risk factors, impaired cholinergic transmission is a main cause for incidence of disease. In the present study, effects of the intracerebroventricularly administration of an agonist of nicotinic cholinergic receptors, varenicline[0.5 and 2 microg/microl], on learning and memory impairments induced by intrahippocampal Abeta[25-35] injection was assessed in rats. The results showed that the intrahippocampal Abeta[25-35] injected rats exhibit lower spontaneous alternation score inY-maze tasks [p<0.05], impaired retention and recall capability in the passive avoidance test [p<0.05], and fewer correct choices [p<0.001] and more errors[p<0.001] in the RAM task. Varenicline, almost in both doses, significantly improved alternation score in Y-maze task [p<0.001], impaired retention and recall capability in the passive avoidance test [p<0.05], and correct choices in the RAM task [p<0.001]. This study indicates that varenicline pretreatment attenuates Abeta- induced impairment of short-term spatial memory in rats probably due to its agonist activity at nicotinic receptors.

[Antinociceptive effect of chronic administration of the flavonoid hesperetin in diabetic rats: behavioral evidence]

This study was designed to investigate the antinociceptive effect of chronic administration of the flavonoid hesperetin in streptozotocin-diabetic rats using formalin and hot tail immersion tests. Rats were divided into 5 control groups, hesperetin-treated control, diabetic, sodium salicylate [SS] -treated diabetic, and hesperetin-and glibenclamide-treated diabetic groups. Hesperetin [10 mg/kg] was administered i. p. one other day 1 week after diabetes induction for 6 weeks. Finally, thermal pain tolerance and nociception were evaluated using hot water tail immersion and formalin tests respectively. Diabetic rats exhibited a higher score of pain at both phases of the formalin test [P<0.05] and hesperetin-treated diabetic rats exhibited a lower nociceptive score at both phases of the test [P<0.05]. Regarding thermal pain tolerance, diabetes significantly reduced tail immersion latency [P<0.01] and hesperetin treatment did produce a significant change in this respect [P<0.05]. Chronic treatment with hesperetin for 6 weeks does mildly increase thermal pain tolerance and reduces chemical nociception in an experimental model of diabetes mellitus and this may be considered as an auxiliary treatment for diabetic hyperalgesia

flavonoid hesperetin alleviates behavioral abnormality in 6-hydroxydopamine rat model of hemi-parkinsonism

Parkinson's disease [PD] is a neuropathologieal and debilitating disorder involving the degeneration of mesencephalic dopaminergieneurons. Neuroproteetive effect of hesperetin has already been reported, therefore, this study examined whether the administration of this flavonoid would attenuate behavioral abnormalities in an experimental model of PD in rat. For this purpose, unilateral intrastriatal 6-hydroxydopamine [6-OHDA, 12.5 microg/5micro1 of saline-ascorbate]-lesioned rats were pretreated i.p. with hesperetin [10 mg/ kg]. It was found out that hesperetin administration attenuates the rotational behavior in lesioned rats. In summary, hesperetin administration attenuates behavioral abnormality in hemiparkinsonian rats and this may be of benefit, along with other therapies, in neurodegenerative disorders including PD

effect of crataegus spp branchlet feeding on endothelium-dependent contractile and relaxatory response of thoracic aorta from diabetic rats

Diabetes mellitus is accompanied with higher incidence of cardiovascular disorders. There is some evidence on antidiabetic and cardiovascular improving potential of Crataegus spp [CS]. Thus, the endothelium-dependent effect of oral administration of CS branchlet for 6 weeks on contractile and relaxatory response of thoracic aorta from diabetic rats was investigated. Male Wistar rats were divided into control, CS-treated control, diabetic, CS-treated diabetic, and glibenclamide-treated diabetic groups. Treated groups received CS-mixed pelleted food at a weight ratio of 6.25%. Body weight and serum glucose level was measured before the study and at weeks 3 and 6. At the end of study, contractile reactivity of thoracic aortic rings to KC1 and phenylephrine and relaxatory response to acetylcholine and sodium nitroprusside was determined using isolated tissue setup. Serum glucose level significantly decreased in CS-treated diabetic group [p<0.01] versus untreated diabetics. In addition, endothelium-intact CS-treated diabetic group showed a significantly lower contraction to KC1 and phenylephrine [p<0.05] as compared to diabetic group and endothelium removal abolished this response. Meanwhile, relaxation response of endothelium-intact rings to acetylcholine was significantly higher in CS-treated diabetic group as compared to diabetics [p<0.05]. In addition, there were no significant changes amongst the groups regarding relaxatory response to sodium nitroprusside. Chronic oral administration of CS through affecting endothelial-related agents could decrease contractile response and enhance relaxatory response in aortic tissue of diabetic rat and this may be beneficial in prevention of long-term vascular complications of diabetes

[ effect of feeding with aerial part of vaccinium myrtillus on blood glucose and lipids of diabetic rats]

Use of medicinal plants for attenuation of hyperglycemia and restoration of lipids to normal levels is very important. The effect of oral administration of Vaccinium myrtillus [VM] on serum glucose and lipids in diabetic rats was investigated. Female Wistar rats were divided into 4 groups: control, VM-treated control, diabetic, and VM-treated diabetic groups. The treatment groups received oral administration of plant-mixed food [6.25%] for 4 weeks. Serum glucose, triglyceride, total cholesterol, LDL- and HDL- cholesterol levels were determined before the study, and at 2nd and 4th weeks after the study. Serum glucose level in diabetic group increased 2 and 4 weeks after the experiment as compared to data one week before the study [P<0.001] and VM treatment of diabetic rats did have a significant hypoglycemic effect [P<0.01]. In addition, triglyceride level in diabetic group increased 4 weeks after the experiment in comparison with related data one week before the study [P<0.05] and there was a significant lower level of triglyceride in VM-treated diabetic rats [P<0.05]. Furthermore, there was no significant changes regarding serum total cholesterol, HDL- and LDL- cholesterol levels in treated diabetic group as compared to untreated diabetic group. Oral administration of VM has a significant hypoglycemic effects and leads to an appropriate changes only in triglyceride level

role of L-type calcium channels in the vascular effect of trigonella foenum-graecum L. in diabetic rats

Some ion channels like voltage-operated calcium channels [VOCC] within the plasma membrane of vascular muscle cells from the walls of resistance arteries and arterioles play a central role in the regulation of vascular tone. On the basis of reports about the beneficial attenuating effect of fenugreek [Trigonella foenum-graecum L.; TFG] on the contractile reactivity of aortic rings of diabetic rats, this study was carried out to evaluate the possible involvement of L-type voltage-operated calcium channels in the vascular effect of this medicinal plant. For this purpose, male Wistar rats were made diabetic using streptozotocin [STZ, 60 mg/Kg, i.p]. The extract-treated control and diabetic rats received aqueous leaf extract of TFG [200 mg/Kg, i.p.] every other day for two months. At the end of the study, contractile response of isolated aortic rings to KC1 and noreadrenaline [NA] was determined in the absence and presence of the calcium channel blocker nifedipine. The results showed that aortic rings from diabetic rats are more responsive to the effect of KC1 and NA than those of controls, TFG extract treatment could attenuate the enhanced contractile response of aortic rings of diabetic rats, and nifedipine pretreatment could partially neutralize the beneficial effect of this extract. It is concluded that TFG extract attenuates the enhanced vascular reactivity in chronic diabetic rats and voltage-operated calcium channels are in part responsible for this effect of TFG extract

Time course of changes in passive aviodance and y-maze performance in male diabetic rats

Diabetes mellitus is accompanied with disturbances in learning, memory, and cognitive skills in the human society and experimental animals. Therefore, this research study was conducted to evaluate time-dependent changes in passive avoidance and Y-maze performance in male diabetic rats. For this purpose, male Wistar rats were randomly divided into control and diabetic groups. For induction of diabetes, streptozotocin [STZ] was injected i.p. at a single dose of 60 mg/kg. For evaluation of learning and memory, initial latency [IL] and step-through latency [STL] were determined at the end of 1[st], 2[nd], and 3[rd] months using passive avoidance and Y-maze tasks. It was found out that mean IL exhibits a significant increase only at the end of 2[nd] [p<0.05] and 3[rd] [p<0.01] months. In addition, STL significantly reduced at the end of 2[nd] [p<0.05] and 3[rd] months [p<0.01]. Regarding Y-maze task, alternation score of the diabetic rats was lower than that of the control ones at the end of 1[st] [p<0.05], 2[nd] [p<0.01], and 3[rd] [p<0.01] months as compared to time-matched control group. To conclude, at least one month is strictly required for development of behavioral disturbances in passive avoidance and Y-maze tasks in STZ-diabetic rats

Green tea polyphenol epigallocatechin-3-Gallate attenuates behavioral abnormality in hemi-parkinsonian rat

Epigallocatechin gallate [EGCG], a major constituent of green tea, has been introduced as a potent free radical scavenger and can effectively reduce free radical-induced lipid peroxidation. Since free radical injury plays an important role in neuronal damage in Parkinson's disease [PD], this study examined whether EGCG administration would reduce functional asymmetry in an experimental model of PD in male Wistar rats. For this purpose, unilateral intrastriatal 6-hydroxydopamine-lesioned rats were intraperitoneally pretreated with EGCG [40 mg/Kg] 2 hours before surgery and daily [20 mg/Kg] for a period of 2 weeks post-surgery. Apomorphine- and amphetamine-induced rotations were measured pre- and post-surgery after 2 weeks. The results showed that there are 35.1% [P<0.05] and 33.2% [P<0.05] reductions in controversies apomorphine- and ipsiversive amphetamine-induced rotations in EGCG-treated-lesioned group respectively as compared to the untreated lesioned group at 2[nd] week post-surgery. Taken together, these results showed that two-week administration of EGCG could attenuate the drug-induced behavioral abnormalities in this model of PD

analgesic effect of oral administration of tarragon in diabetic rats

Hyperalgesia is one of the major symptoms of diabetic neuropathy in some patients and could affect life quality. Regarding treatment of hyperalgesia, there are some evidence for antidiabetic potential of tarragon in traditional medicine. To evaluate the analgesic effect of oral administration of tarragon in streptozotocin-induced diabetic male rats. This was an experimental study in which 40 rats were randomly divided into control, tarragon-treated control, salicylate-treated control, diabetic, and tarragon-treated diabetic groups. All treatment periods continued for one month. At the end of the experiment, nociceptive response was evaluated in both acute and chronic phases of the standard formalin test. The results showed that there was an increase in the pain scores in both phases of the test and in diabetic rats [P<0.05], and administration of tarragon for one month did produce a significant reduction in nociceptive scores for both phases, especially in the chronic phase of the formalin test [P<0.05]. In contrast, sodium salicylate as positive control only reduced pain scores in the chronic phase [P<0.05]. Oral administration of tarragon for one month has a significant analgesic effect in diabetic rats and this may be considered as a potential treatment for diabetic neuropathy

Quinapril attenuates the effect of long-term L-NAME administration on the vascular reactivity of diabetic rats

Angiotensin-converting enzyme [ACE] inhibitors including quinapril could exert a protective effect on cardiovascular system through endothelial system in normoglycemic and diabetic rats. The present experimental work was designed to study the vascular reactivity of aortic ring segments isolated from streptozotocin [STZ]-diabetic rats treated for 4 weeks with nitro-L-arginine-methyl ester [L-NAME; 50 mg/100 ml] or L-NAME plus quinapril [10 mg/100 ml] in drinking water. The results showed that quinapril treatment significantly attenuated the augmented contractile response to phenylephrine and KC1 in diabetic rats. In addition, quinapril treatment partially restored the reduced contractile response in diabetic animals treated chronically with L-NAME. It can be concluded that quinapril could partly counteract the effect of long-term L-NAME administration on vascular reactivity in STZ-diabetic rats