Bahadir Suleyman

Biochemically and histopathologically comparative review of thiamine's and thiamine pyrophosphate's oxidative stress effects generated with methotrexate in rat liver

Summary Background Oxidative liver injury occurring with methotrexate restricts its use in the desired dose. Therefore, whether or not thiamine and thiamine pyrophosphate, whose antioxidant activity is known, have protective effects on oxidative liver injury generated with methotrexate was comparatively researched in rats using biochemical and histopathological approaches. Material/Methods Thiamine pyrophosphate+methotrexate, thiamine+methotrexate, and methotrexate were injected intraperitoneally in rats for 7 days. After this period, all animals’ livers were excised, killing them with high-dose anesthesia, and histopathologic and biochemical investigations were made. Result Biochemical results demonstrated a significant elevation in level of oxidant parameters such as MDA and MPO, and a reduction in antioxidant parameters such as GSH and SOD in the liver tissue of the methotrexate group. Also, the quantity of 8-OHdG/dG, a DNA injury product, was higher in the methotrexate group with high oxidant levels and low antioxidant levels, and the quantity of 8-OHdG/dG was in the thiamine pyrophosphate group with low oxidant levels and high antioxidant levels. In the thiamine and control groups, the 8-OHdG/dG rate was 1.48±0.35 pmol/L (P>0.05) and 0.55±0.1 pmol/L (P<0.0001). Thiamine pyrophosphate significantly decreased blood AST, ALT and LDH, but methotrexate and thiamine did not decrease the blood levels of AST, ALT and LDH. Histopathologically, although centrilobular necrosis, apoptotic bodies and inflammation were monitored in the methotrexate group, the findings in the thiamine pyrophosphate group were almost the same as in the control group. Conclusions Thiamine pyrophosphate was found to be effective in methotrexate hepatotoxicity, but thiamine was ineffective.

Effect of Mirtazapine on Oxidative Stress Created in Rat Kidneys by Ischemia-Reperfusion

Abstract In this study, the effect of mirtazapine on rat kidneys versus ischemia-reperfusion (IR) damage was biochemically and histopathologically investigated. The results have shown that malondialdehyde (MDA) level of healthy rat group is 15.2 mol/g protein. The level of this substance was measured as 26.7 mol/g in only ischemia group. The MDA levels of IR and mirtazapine + renal ischemia-reperfusion (MRIR) groups were 39 ± 17.6 mol/g protein. While myeloperoxidase activity of healthy rat group was 20.2 u/g, the activities of only ischemia, IR, and MRIR groups were 28, 36.3, and 21 u/g, respectively. The glutathione levels were measured as 17.7, 12.8, 7.5, and 16.2 nmol/g in healthy, only ischemia, IR, and MRIR groups, respectively. Finally, glutathione S-transferase activities of healthy, only ischemia, IR, and MRIR groups were determined as 20, 13.8, 7.1, and 18.3 u/g, respectively. Histopathologically, while hemorrhage in interstitial area was observed in only ischemia group, significant tubular epithelial swelling, necrosis, and cast accumulation were seen in IR group. In MRIR group, only mild tubular epithelial swelling and mild hyaline cast accumulation were observed in kidney tissue. Consequently, it can be said that mirtazapine has a protective effect on IR-induced kidney damage.

Antiulcerative effect of dexmedetomidine on indomethacin-induced gastric ulcer in rats

A gastroprotective effect occurs when α(2) receptors are innervated. The dextro isomer of medetomidine, dexmedetomidine, is a highly selective α(2)-adrenoreceptor agonist. The aim of this study was to investigate whether dexmedetomidine has an antiulcerative effect and to show whether the antiulcer mechanism of dexmedetomidine is linked with oxidant/antioxidant parameters. The antiulcerative effect of dexmedetomidine was studied in an indomethacin-induced ulcer model, and some oxidant/antioxidant parameters were measured in these gastric tissues. Whereas the average ulcerous areas for the groups that received 10, 25, 50, and 100 μg/kg dexmedetomidine doses were 29 ± 4.2, 8 ± 2.1, 0 ± 0 and 0 ± 0 mm(2), respectively, the ulcerous area was 52.1 ± 4.5 mm(2) in the indomethacin control group and 0.5 ± 0.2 mm(2) in the famotidine group. In conclusion, the α(2)-adrenoreceptor agonist dexmedetomidine showed a significant antiulcerative effect in rat gastric tissue at all doses. This antiulcerative effect is stronger with increasing dosage; at the 50 and 100 μg/kg doses, no ulcerous areas were observed. In light of these results, we conclude that there is a correlation between antiulcer mechanisms and α(2)-receptor activation. In rats given dexmedetomidine, all of the investigated antioxidant parameters increased, except for catalase (CAT). Conversely, aside from myeloperoxidase (MPO), all oxidant parameters decreased. Therefore, oxidant/antioxidant parameters play a role in the antiulcer mechanism of dexmedetomidine.

Effect of Mirtazapine on MNNG-Induced Gastric Adenocarcinoma in Rats

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.

Influence of adrenal hormones in the occurrence and prevention of stress ulcers

PURPOSE The aim of the study was to examine whether endogenous cortisol and adrenalin have a role in the formation of stress ulcers in intact and adrenalectomized rats. METHODS The study was composed of 4 experiments: ulcerated areas in stomachs of adrenalectomized and intact rats were measured, adrenaline (100 μg/kg) and prednisolone (5 mg/kg) were injected intraperitoneally in adrenalectomized rats, metyrapone (200 mg/kg) and metyrosine (200 mg/kg) were administered to intact rats, and metyrapone (200 mg/kg) and metyrosine (200 mg/kg) were administered orally with yohimbine (10 mg/kg) and yohimbine (10 mg/kg) alone were administered to intact rats. After 24-hour restraint stress, ulcerated areas were measured. RESULTS In the stomach of intact rats, the degree of stress ulcer was 7.25 times more severe than that noted in adrenalectomized rats. Furthermore, stress ulcers in adrenalectomized rats that received adrenaline or prednisolone only were fewer and less severe than rats receiving both adrenaline and prednisolone. CONCLUSIONS Simultaneous administration of adrenaline and prednisolone did not prevent the formation of stress ulcers. However, either of these hormones alone (adrenaline or prednisolone), in the absence of the other, repressed the formation of stress ulcers. This antiulcer activity may be related to α2-adrenergic receptor activity.

The Effect of Anakinra on Paclitaxel-Induced Peripheral Neuropathic Pain in Rats

OBJECTIVE Paclitaxel is used in the treatment of cancer, and it may cause interleukin-1 beta (IL-1β)-related peripheral neuropathic pain. While our primary aim was to investigate the analgesic efficacy of an IL-1β antagonist, a secondary outcome was to assess whether a correlation exists between analgesic effects and antioxidant activity. METHODS A total of 24 albino Wistar male rats were divided into the following groups: paclitaxel-control, paclitaxel+50 mg kg-1 anakinra, paclitaxel+100 mg kg-1 anakinra and healthy group (HG). After the normal paw pain threshold in all animal groups was measured using a Basile algesimeter, a single dose of 2 mg kg-1 paclitaxel was intraperitoneally administered on the 1st, 3rd, 5th and 7th days. Anakinra was intraperitoneally administered following the final paclitaxel administration. The paw pain thresholds in the groups were measured before and seven days after paclitaxel administration and at the 1st and 3rd hours after anakinra administration. After the third hour of measurement, the rats were killed with high doses of ketamine, and the paw tissues were removed. Malondialdehyde, myeloperoxidase and total glutathione levels were measured in claw tissues, and IL-1β gene expression was determined. The biochemical results were compared with the results of the HG; in the meanwhile the claw pain threshold results were compared with the results obtained after the last paclitaxel and the results obtained from the 1st and 3rd hours after the anakinra application. RESULTS The claw paw pain threshold of the rats decreased one and three hours after anakinra administration. Further, 100 mg kg-1 anakinra had greater analgesic activity than 50 mg kg-1 anakinra. A correlation was found between the antioxidant and analgesic activities of 100 mg kg-1 anakinra. CONCLUSION Anakinra may be useful to reduce paclitaxel-induced neuropathic pain; further, 100 mg kg-1 anakinra may have greater analgesic and antioxidant activities.

The effects of ketamine and thiopental used alone or in combination on the brain, heart, and bronchial tissues of rats

Introduction We compared the side effects of ketamine and thiopental used alone and of a ketamine/thiopental combination dose on the brain,heart, and bronchial tissues of rats. Material and methods Three groups received intraperitoneal injections of 30 mg/kg ketamine (K-30); 15 mg/kg thiopental (T-15); or of both in combination (KTSA). These doses were doubled in another set of study groups (K-60, T-30, and KTA groups, respectively). Optimal anesthesia duration was examined in all groups. Results Anesthesia did not occur with 30 mg/kg ketamine or 15 mg/kg thiopental. However, when used alone ketamine and thiopental led to oxidative stress in the striatum, heart, and bronchial tissues. Conversely, combined administration of anesthetics and subanesthetic doses were found not to create oxidative stress in any of these areas. The highest level of adrenaline in blood samples collected from the tail veins was measured in the KTA-60, and the lowest amount in the T-30. Creatine kinase activity was highest in the KTA-60 group (p < 0.001). When we compared for all 5 groups to untreated control group; the creatine kinase-MB activities were significiantly different in K-30, T-15 and T-30 (p < 0.001). Conclusions The studied doses of ketamine led to oxidative stress by increasing the amount of adrenaline. Thiopental increased oxidative stress with decreases in adrenaline. A longer anesthetic effect with minimal adverse events may be achieved by ketamine and thiopental in combination.