Effects of Calcium Channel Blockers On Hyaluronidaseinduced Capillary Vascular Permeability

Halici, Zekai,Suleyman, Halis,Cadirci, Elif 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.7

Inflammation and increased capillary permeability is a significant aspect of the pathogenesis of many diseases including atherosclerosis. L-type calcium channel blockers (CCB) are commonly used as cardiovascular drugs. Amlodipine, lacidipine, and nicardipine were evaluated for anti-inflammatory activity on the paw oedema produced by carrageenan. The effect of these drugs was compared with the activity of indomethacin. Their effects on vascular permeability were also tested by hyaluronidase-induced capillary permeability. In our animal experiments, amlodipine decreased the carrageenan-induced paw oedema at doses of 1, 3, and $6\;mg\;kg^{-1}$ by 27.3%, 43.7%, and 67.3% four hour after carrageenan administration; the same doses of lacidipine and nicardipine decreased paw oedema by 37.1%, 55.6%, 76.4%, 11.2%, 31.0%, 91%; and indomethacin decreased oedema by 38.2% at a dose of $6\;mg\;kg^{-1}$. Lacidipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at doses of 1, 3, and $6\;mg\;kg^{-1}$ compared with the control group. However, amlodipine and nicardipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at 3 and $6\;mg\;kg^{-1}$ doses. A $6\;mg\;kg^{-1}$ dose of indomethacin significantly decreased the capillary permeability which was increased by hyaluronidase. These results suggest that CCBs can be efficient anti-inflammatories, and can also significantly decrease capillary permeability.

Effects of Calcium Channel Blockers On Hyaluronidaseinduced Capillary Vascular Permeability

Zekai Halici,Halis Suleyman,Elif Cadirci 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.7

Inflammation and increased capillary permeability is a significant aspect of the pathogenesis of many diseases including atherosclerosis. L-type calcium channel blockers (CCB) are commonly used as cardiovascular drugs. Amlodipine, lacidipine, and nicardipine were evaluated for anti-inflammatory activity on the paw oedema produced by carrageenan. The effect of these drugs was compared with the activity of indomethacin. Their effects on vascular permeability were also tested by hyaluronidase-induced capillary permeability. In our animal experiments, amlodipine decreased the carrageenan-induced paw oedema at doses of 1, 3, and 6 mg kg-1 by 27.3%, 43.7%, and 67.3% four hour after carrageenan administration; the same doses of lacidipine and nicardipine decreased paw oedema by 37.1%, 55.6%, 76.4%, 11.2%, 31.0%, 91%; and indomethacin decreased oedema by 38.2% at a dose of 6 mg kg-1. Lacidipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at doses of 1, 3, and 6 mg kg-1 compared with the control group. However, amlodipine and nicardipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at 3 and 6 mg kg-1 doses. A 6 mg kg-1 dose of indomethacin significantly decreased the capillary permeability which was increased by hyaluronidase. These results suggest that CCBs can be efficient anti-inflammatories, and can also significantly decrease capillary permeability.

Effect of Mirtazapine on MNNG-Induced Gastric Adenocarcinoma in Rats

Bilici, Mehmet,Cayir, Kerim,Tekin, Salim Basol,Gundogdu, Cemal,Albayrak, Abdulmecit,Suleyman, Bahadir,Ozogul, Bunyamin,Erdemci, Burak,Suleyman, Halis Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

Objective: In this study, anticancer effects of mirtazapine on rats were investigated in an adenocarcinoma model induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and compared with those of cisplatin. Materials and Methods: For this purpose, 10 mg/kg doses of mirtazapine were administered orally to one group of rats, while 1 mg/kg doses of cisplatin were administered intraperitoneally to another group. At 1 hour after administration, 200 mg/kg doses of MNNG were given orally to both groups. MNNG administration was repeated once every 10 days through 3 months, after which period, gastric tissue was taken and pathologically evaluated. Results: Mirtazapine prevented adenocarcinoma induction by MNNG in rats to a greater extent than cisplatin. Some of the rats receiving cisplatin demonstrated severe dysplasia in gastric samples and others exhibited mild dysplasia. Rats given mirtazapine were not observed to suffer severe dysplasia, only mild dysplasia being observed. Conclusion: For adenocarcinoma induced by MNNG on rats, mirtazapine was determined more effective than cisplatin. In order to make statement about mechanism of anticancer activity of mirtazapine, wider studies are required.

A comparative investigation of biochemical and histopathological effects of thiamine and thiamine pyrophosphate on ischemia– reperfusion induced oxidative damage in rat ovarian tissue

Ismail Demiryilmaz,Ebru Sener,Nihal Cetin,Durdu Altuner,Fatih Akcay,Halis Suleyman 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.9

In this study, the biochemical and histopathologicaleffects of thiamine and thiamine pyrophosphate onischemia–reperfusion induced oxidative damage in ratovarian tissue were investigated. Animals were divided intofour groups of six rat each, ovarian ischemia–reperfusion(IR), 25 mg/kg thiamine ? ovarian ischemia–reperfusion(TIR), 25 mg/kg thiamine pyrophosphate ? ovarian ischemia–reperfusion (TPIR) and Sham group (SG). The resultsof the biochemical experiments have shown that the ratovarian tissue with thiamine treatment, the level of MDA,GSH and the 8-hydroxyguanine are almost the same as theIR group; while in the group with thiamine pyrophosphatetreatment, the level of MDA, GSH and the 8-hydroxyguanineare almost the same as the SG. Ovarian tissue of rats inthe IR group were congested and dilated vessels, edema,hemorrhage, necrotic and apoptotic cells. In this group, themigration and the adhesion of the polymorphonuclear leucocytesto the endothelium were observed. Both ovaries inTPIR group, there was no difference according to the SG. Histopathology of ovarian tissues in the TIR group wasalmost the same with the IR group. Our results indicate thatthiamine pyrophosphate significantly prevents the ischemia–reperfusion induced oxidative damage in ovarian tissue,whereas thiamine has no effect. In conclusion, we havefound that thiamine pyrophosphate prevents oxidativedamage due to ischemia–reperfusion injury, whereasthiamine does not have this effect. Furthermore, we haveconfirmed that the results of our biochemical analyses are inconcordance with the histopathological findings.

Effects of Epinephrine and Cortisol on the Analgesic Activity of Metyrosine in Rats

Yavuz Albayrak,Mustafa Bahadir Saglam,Kadir Yildirim,Saliha Karatay,Beyzagul Polat,Turan Uslu,Fatih Akcay,Halis Suleyman 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.9

Some endogenous hormones (epinephrine and cortisol) can change an individual’s pain threshold. Propranolol is a non-selective β adrenergic receptor blocker which antagonises the antiinflammatory effect of non-steroidal anti-inflammatory drugs via the β1 and β2 adrenergic receptors. The roles of epinephrine and cortisol were investigated in the analgesic activity of metyrosine in rats with reduced epinephrine levels induced by metyrosine. Pain threshold measurement was performed using an analgesimeter with different doses and the single or combined usage of metyrosine, prednisolone, metyrapone and propranolol in rats. Epinephrine and corticosterone levels were measured by high-performance liquid chromatography in metyrosine-administered rats. Metyrosine reduces the epinephrine levels without affecting the corticosterone levels, thereby creating an analgesic effect. It was determined that prednisolone did not have an analgesic effect in rats with normal epinephrine levels, but its analgesic activity increased with a parallel decrease in the epinephrine levels. Similarly, the combined use of prednisolone and metyrosine provided a stronger analgesic effect than that rendered by metyrosine alone. The strongest analgesic effect, however, was observed in the group of rats with the lowest epinephrine level in whom the metyrosine + prednisolone combination was administered. The findings of this study may be useful in severe pain cases in which the available analgesics are unable to relieve the individual’s pain.

The effect of adenosine triphosphate on propofol-induced myopathy in rats: a biochemical and histopathological evaluation

Kezban Tuna Ozkaloglu Erdem,Zehra Bedir,Irem Ates,Ufuk Kuyrukluyildiz,Taha Abdulkadir Coban,Gulce Naz Yazici,Yusuf Kemal Arslan,Zeynep Suleyman,Halis Suleyman 대한약리학회 2021 The Korean Journal of Physiology & Pharmacology Vol.25 No.1

Propofol infusion syndrome characterized by rhabdomyolysis, metabolic acidosis, kidney, and heart failure has been reported in long-term propofol use for sedation. It has been reported that intracellular adenosine triphosphate (ATP) is reduced in rhabdomyolysis. The study aims to investigate the protective effect of ATP against possible skeletal muscle damage of propofol in albino Wistar male rats biochemically and histopathologically. PA-50 (n = 6) and PA-100 (n = 6) groups of animals was injected intraperitoneally to 4 mg/kg ATP. An equal volume (0.5 ml) of distilled water was administered intraperitoneally to the P-50, P-100, and HG groups. One hour after the administration of ATP and distilled water, 50 mg/kg propofol was injected intraperitoneally to the P-50 and PA-50 groups. This procedure was repeated once a day for 30 days. The dose of 100 mg/kg propofol was injected intraperitoneally to the P-100 and PA-100 groups. This procedure was performed three times with an interval of 1 days. Our experimental results showed that propofol increased serum CK, CK-MB, creatinine, BUN, TP I, ALT, AST levels, and muscle tissue MDA levels at 100 mg/kg compared to 50 mg/kg and decreased tGSH levels. At a dose of 100 mg/kg, propofol caused more severe histopathological damage compared to 50 mg/kg. It was found that ATP prevented propofol-induced muscle damage and organ dysfunction at a dose of 50 mg/kg at a higher level compared to 100 mg/kg. ATP may be useful in the treatment of propofol-induced rhabdomyolysis and multiple organ damage.