The role of polymorphonuclear leukocytes in distant organ (lung) oxidative damage of liver ischemia/reperfusion and the protective effect of rutin.

BACKGROUND: Ischemia/reperfusion (I/R) can cause damage to distant organs. Rutin is known to have antioxidant and anti-inflammatory properties, and inhibits cytokine and polymorphonuclear leukocyte (PMNL) infiltration. It may prevent the development of reperfusion injury. OBJECTIVES: This study aimed to examine the role of PMNLs in distant organ (lung) injury after a liver I/R procedure, and to evaluate the protective effects of rutin in rats using biochemical and immunohistochemical methods. MATERIAL AND METHODS: In this study, 18 Wistar albino male rats (255-275 g) were used. Experimental animals were divided into 3 groups: a liver I/R (LIR) group, a 50 mg/kg rutin+liver I/R (RLIR) group and a sham operation (SG) control group. Experimental results obtained from the RLIR group were compared with the LIR and SG groups. RESULTS: Blood malondialdehyde (MDA) levels in the RLIR and SG groups were significantly lower compared to the LIR group (p < 0.001). Blood myeloperoxidase (MPO) activity in the RLIR and SG groups was significantly lower compared to the LIR group (p < 0.001). Total glutathione (tGSH) levels in the RLIR and SG groups were significantly higher compared to the LIR group (p < 0.001). CONCLUSIONS: Rutin can be used to prevent distant organ (lung) damage due to liver I/R. However, more extensive studies are needed on this issue.

Oxidative and pro-inflammatory lung injury induced by desflurane inhalation in rats and the protective effect of rutin.

BACKGROUND: Desflurane is a mainstay of general inhaled anesthetics with a methyl ethyl ether structure and is widely used in clinical practice. It has been reported to induce inflammation and lipid peroxidation in rat pulmonary parenchyma, to increase alveolar macrophages, and to cause peribronchial infiltration and edema. Rutin, a flavonoid vitamin P1, is known to have biological properties including acting as an antioxidant, an anti-inflammatory, and an inhibitor of bronchoalveolar polymorphonuclear leukocyte (PNL) infiltration. OBJECTIVES: The aim of this study is to examine the effects of rutin on desflurane-induced pulmonary injury using biochemical and histopathological methods. MATERIAL AND METHODS: The rats were divided into 3 groups (n = 6 each): healthy control (HC), rutin+desflurane-treated (DRT) and desflurane-only (DSF). Briefly, 50 mg/kg of rutin was given orally to the DRT group and an equal volume of normal saline was given to the DSF and HC groups. After 1 h, anesthesia was induced and maintained in the DRT and DSF groups for 2 h. After the rats had been sacrificed, the lungs were removed. Malondialdehyde (MDA), total glutathione (GSH), tumor necrosis factor alpha (TNF-α), and nuclear factor kappa B (NF-κB) levels were measured in the excised lung tissue. The removed tissues were also fixed in 10% formalin, and the obtained sections were stained with hematoxylin and eosin (H&E) and evaluated under light microscopy. The biochemical and histopathological results of the DRT group were compared with those obtained from the DSF and HC groups. RESULTS: Desflurane increased MDA, TNF-α and NF-κB, and decreased GSH in lung tissue. The PNL infiltration, alveolar macrophages, hemorrhage, alveolar damage, and edema were observed in the lung tissue of the DSF group. Rutin was histopathologically shown to protect lung tissue from oxidative stress by preventing an increase in oxidant parameters and a decrease in antioxidants. CONCLUSIONS: The results suggest that rutin may be useful in the treatment of desflurane-associated lung injury.

The investigation of the protective effects of nimesulide on experimental testicular ischemia-reperfusion injury in rats / La investigación de los efectos protectores de nimesulida en la lesión de isquemia y reperfusión testicular experimental en ratas

INTRODUCTION AND OBJECTIVES: Testicular ischemia/reperfusion (I/R) injury develops after torsion and following detorsion of the testis. Reactive oxygen species were produced and oxidative damage begins to occur due to I/R process. Nimesulide, which is a specific cyclooxygenase-2 inhibitor drug, have antioxidant, antiinflammatory, analgesics and antipyretic effects. We aimed to investigate biochemically and histopathologically effect of nimesulide on testis I/R injury in rats induced by the testicular torsion-detorsion. MATERIAL AND METHODS: In this study, 24 albino Wistar male rats were divided into four groups (6 rats in each group): ischemia/reperfusion applied+50mg/kg nimesulide administrated (NIM-50), ischemia/reperfusion applied+100mg/kg nimesulide administrated (NIM-100), ischemia/reperfusion applied (IR) and Sham surgery (SS) groups. Nimesulide was administered to NIM-50 and NIM-100 groups at the 50mg/kg and 100mg/kg doses before 2h applied I/R procedures. The IR group were applied only I/R procedures, no drug treatment was applied. Animals were sacrificed under high dose anesthesia and left testes were extracted. Testes were examined biochemically and histopathologically. RESULTS: Total glutathione (tGSH) and cyclooxygenase-1 (COX-1) levels were increased in the NIM-50 and NIM-100 groups compared to IR group. The levels of COX-2, malondialdehyde (MDA), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were lower in the NIM-50 and NIM-100 groups than in the IR group. Some histopathological changes seen in IR group. This findings were decreased in NIM-50 group and prevented in NIM-100 group. CONCLUSION: Nimesulide prevented inflammation and oxidative stress. Our results suggest that nimesulide may be have a protective effect on testicular I/R injury

INTRODUCCIÓN Y OBJETIVOS: La lesión de isquemia y reperfusión testicular (I/R) se desarrolla después de la torsión y la consiguiente detorsión del testículo. Se produjeron especies reactivas de oxígeno y el daño oxidativo comienza a producirse debido al proceso de I/R. La nimesulida, que es un fármaco inhibidor específico de la ciclooxigenasa 2, tiene efectos antioxidantes, antiinflamatorios, analgésicos y antipiréticos. El objetivo fue investigar el efecto bioquímico e histopatológico de la nimesulida sobre la lesión testicular I/R en ratas inducida por la torsión-detorsión testicular. MATERIAL Y MÉTODOS: En este estudio se dividió a 24 ratas albinas Wistar macho en 4 grupos (6 ratas en cada grupo): isquemia y reperfusión aplicada+50mg/kg de nimesulida administrada (NIM-50), isquemia y reperfusión aplicada+100mg/kg de nimesulida administrada (NIM-100), isquemia y reperfusión aplicada (IR) y cirugía simulada (SS). La nimesulida se administró a los grupos NIM-50 y NIM-100 a las dosis de 50 y 100mg/kg, respectivamente, 2h antes de aplicar los procedimientos de I/R. Al grupo IR se aplicó solo procedimientos I/R, no se aplicó tratamiento farmacológico. Los animales se sacrificaron con anestesia a dosis altas y se extrajeron los testículos izquierdos. Los testículos se examinaron bioquímicamente e histopatológicamente. RESULTADOS: Los niveles totales de glutatión (tGSH) y ciclooxigenasa-1 (COX-1) aumentaron en los grupos NIM-50 y NIM-100 en comparación con el grupo IR. Los niveles de COX-2, malondialdehído (MDA), interleucina 1β (IL-1β) y factor de necrosis tumoral-α (TNF-α) fueron menores en los grupos NIM-50 y NIM-100 que en el grupo IR. Se vieron algunos cambios histopatológicos en el grupo IR. Estos hallazgos disminuyeron en el grupo NIM-50 y se evitaron en el grupo NIM-100. CONCLUSIÓN: La nimesulida previno la inflamación y el estrés oxidativo. Nuestros resultados sugieren que la nimesulida puede tener un efecto protector sobre la lesión testicular I/R

Peripheral neurotoxic effects of cisplatin on rats and treatment with rutin.

BACKGROUND: Cisplatin, used in cancer treatment, has toxic and apoptotic effects on the peripheral nervous system. Rutin, also known as vitamin P, has antioxidant and antiapoptotic activity. OBJECTIVES: The purpose of this study was to investigate the biochemical and histopathologic efficacy of rutin on neurotoxic and apoptotic effects caused by cisplatin in the peripheral nervous system. MATERIAL AND METHODS: Twenty-four albino Wistar male rats were divided into the following 4 groups: control group (CG), only cisplatin-injected group (CIS), cisplatin and rutin 50 mg/kg (RG-50)-injected group, and cisplatin and rutin 100 mg/kg (RG-100)-injected group. Analyses were performed on sciatic nerve tissue of experimental animals. Analyses of malondialdehyde (MDA), total glutathione (tGSH), glutathione reductase (GSHRd), glutathione-s-transferase (GST), and superoxide dismutase (SOD) were performed. Caspase-3 expression in nerve tissue was also investigated. The analyzed groups were compared with CG. RESULTS: Biochemical investigation shows that there is a statistically significant difference between CG and only CIS and RG-50. Control group and RG-100 were found to be similar. Cisplatin-induced changes were observed in histopathological analysis of the nerve tissue. The RG-100 and CG were found to be similar. The caspase-3 expression in the neural tissue was compared between groups. Control group and CIS were found to be different. Control group and RG-100 were found to be similar. CONCLUSIONS: Antioxidant and antiapoptotic effectiveness of rutin was detected against the toxic effects caused by cisplatin in the peripheral nerve tissue.

Effect of lutein on methotrexate-induced oxidative lung damage in rats: a biochemical and histopathological assessment.

BACKGROUND/AIMS: This study aimed to investigate the effect of lutein on methotrexate (MTX)-induced pulmonary toxicity in rats biochemically and histopathologically. METHODS: The rats in the MTX + lutein (MTXL, n = 6) group were given 1 mg/kg of lutein orally. A 0.9% NaCl solution was administered orally to the MTX (n = 6) group and the healthy group (HG, n = 6). One hour later, a single 20 mg/kg dose of MTX was injected intraperitoneally in the MTXL and MTX. Lutein or 0.9% NaCl solution was administered once a day for 5 days. At the end of this period, malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH), interleukin 1 beta (IL-1ß), and tumor necrosis factor alpha (TNF-α) were measured in the lung tissues from the animals euthanized with 50 mg/kg thiopental sodium anesthesia. Subsequently, histopathological examinations were performed. RESULTS: The levels of MDA, MPO, IL-1ß, and TNF-α in the lung tissue of the MTX were significantly higher than those of the MTXL and HG groups (p < 0.0001), and the amount of tGSH was lower. The histopathological findings in the MTX group, in which the oxidants and cytokines were higher, were more severe. CONCLUSION: Lutein prevented the MTX-induced oxidative lung damage biochemically and histopathologically. This result indicates that lutein may be useful in the treatment of MTX-induced lung damage.

The effects of thiamine pyrophosphate on ethanol induced optic nerve damage.

BACKGROUND: We aimed to determine the protective effects of thiamine pyrophosphate on ethanol induced optic neuropathy in an experimental model. METHODS: The rats were assigned into 4 groups, with 6 rats in each group as follows: healthy controls (HC group), only ethanol administered group (EtOH group), ethanol + thiamine pyrophosphate (20 mg/kg) administered group (TEt-20 group), and only thiamine pyrophosphate (20 mg/kg) (TPG group) administered group. To the rats in TEt-20 and TPG groups, 20 mg/kg thiamine pyrophosphate was administered via intraperitoneal route. To the rats in HC and EtOH groups, the same volume (0.5 ml) of distilled water as solvent was applied in the same manner. To the rats in TEt-20 and EtOH groups, one hour after application of thiamine pyrophosphate or distilled water, 32% ethanol with a dose of 5 g/kg was administered via oral gavage. This procedure was repeated once a day for 6 weeks. From the blood samples and tissues obtained from the rats, Malondialdehyde (MDA), reduced glutathione (GSH), interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) levels were studied. Histopathological evaluations were performed to the optic nerve tissue. RESULTS: Serum and tissue IL-1ß, TNF-α and MDA levels were the highest in EtOH group which were significantly lower in thiamine pyrophosphate administered group (TEt-20 group) (p: 0.001). Serum and tissue reduced GSH levels were the lowest in EtOH group which were also significantly higher in TEt-20 group (p:0.001). In histopathological evaluations, in EtOH group there was obvious destruction and edema with hemorrhage and dilated blood vessels which were not present in any other groups. CONCLUSIONS: There was an apparent destruction in ethanol administered group in histopathological analyses with an augmented level of oxidative stress markers and all those alterations were prevented with concomitant thiamine pyrophosphate administration. These protective effects of thiamine pyrophosphate are extremely important in chronic ethanol consumption. Clinical studies are warranted to define the exact role of thiamine pyrophosphate in prevention of ethanol induced optic neuropathy.

Effect of taxifolin on oxidative gastric injury induced by celiac artery ligation in rats.

PURPOSE: To examine the effect of taxifolin on I/R induced gastric injury in rats using biochemical and histopatholohical methods. METHODS: Eighteen albino Wistar male rats equally grouped as; gastric I/R (I/R), 50 mg/kg taxifolin + gastric I/R (TAX+ I/R) and sham operation applied (SHAM). Ischemia induced for 1 hour, and reperfusion induced for 3 hours. RESULTS: Oxidant parameters like, Malondialdehyde (MDA) and Hydroxyguanine (8-OHdG) were higher, whereas total glutathione (tGSH) was lower in the I/R group according to SHAM group, histopathological findings such as marked destruction, edema, and proliferated dilated congested blood vessels were observed severely in the I/R group, whereas there was not any pathological finding except mild dilated congested blood vessels in the TAX+ I/R group. CONCLUSION: The taxifolin can be clinically beneficial in the treatment of gastric injury due to I/R procedure.

The Effect of Taxifolin on Cisplatin-Induced Pulmonary Damage in Rats: A Biochemical and Histopathological Evaluation.

The effect of taxifolin on cisplatin-induced oxidative pulmonary damage was investigated biochemically and histopathologically in male albino Wistar rats. There were four groups, with six animals in each group: 50 mg/kg of taxifolin plus 2.5 mg/kg of cisplatin (TC) group, 2.5 mg/kg of cisplatin only (CIS) group, 50 mg/kg of taxifolin only (TG) group, and a healthy control group (HG). In terms of the experimental procedure, the animals in the TC and TG groups were first treated via oral gavage. The CIS and HG groups received distilled water as solvent, respectively. One hour later, the TC and CIS groups received cisplatin at a dose of 2.5 mg/kg (injected intraperitoneally). Taxifolin, cisplatin, and the distilled water were administered at the indicated dose and volume, using the same method daily for 14 d. At the end of this period, the animals were killed with a high dosage of thiopental anaesthesia (50 mg/kg). Blood and lung tissue samples were taken for biochemical (malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH), and 8-hydroxy-2 deoxyguanosine (8-OHdG)) analyses and histopathological examinations. The biochemical and histopathological results in the TC and HG groups were then compared with those in the CIS group. Cisplatin increased the levels of MDA, myeloperoxidase, and 8-OHdG, a marker of oxidative DNA damage, and reduced the amount of tGSH in the lung tissue. Moreover, severe alveolar damage, including oedema and extensive alveolar septal fibrosis, in addition to infiltration of polymorphic nuclear leucocytes and haemorrhagic foci, was observed in the CIS group. These histopathological findings demonstrate that taxifolin provides protection against pulmonary oxidative stress by preventing increases in oxidant parameters and decreases in antioxidants.

Effect of taxifolin on oxidative gastric injury induced by celiac artery ligation in rats

Abstract Purpose: To examine the effect of taxifolin on I/R induced gastric injury in rats using biochemical and histopatholohical methods. Methods: Eighteen albino Wistar male rats equally grouped as; gastric I/R (I/R), 50 mg/kg taxifolin + gastric I/R (TAX+ I/R) and sham operation applied (SHAM). Ischemia induced for 1 hour, and reperfusion induced for 3 hours. Results: Oxidant parameters like, Malondialdehyde (MDA) and Hydroxyguanine (8-OHdG) were higher, whereas total glutathione (tGSH) was lower in the I/R group according to SHAM group, histopathological findings such as marked destruction, edema, and proliferated dilated congested blood vessels were observed severely in the I/R group, whereas there was not any pathological finding except mild dilated congested blood vessels in the TAX+ I/R group. Conclusion: The taxifolin can be clinically beneficial in the treatment of gastric injury due to I/R procedure.

The effect of anakinra to nephrotoxicity with cisplatin induced in rats: Biochemical, gene expression and histopathological evaluation.

BACKGROUND: Oxidative stress and interleukin-1 beta (IL-1ß) have been reported to play a role in the pathogenesis of nephrotoxicity induced by cisplatin. OBJECTIVES: The objective of this study was to investigate the effect of anakinra, which is an IL-1ß receptor antagonist, on cisplatin-induced nephrotoxicity in rats, through biochemical, gene expression and histopathological analyses. MATERIAL AND METHODS: The study was designed with 4 groups. For 1 week, the control group (C) and the cisplatin (Cis) group received distilled water, while the cisplatin + anakinra 50 (Cis + ANA50) group and the cisplatin + anakinra 100 (Cis + ANA100) group were intraperitoneally administered 50 mg/kg and 100 mg/kg of anakinra, respectively. The Cis, Cis + ANA50 and Cis + ANA100 groups were intraperitoneally injected with a 2.5 mg/kg dose of cisplatin for 7 days. After sacrifice, the kidney tissue of each rat was extracted for the assessment of the malondialdehyde (MDA) and total glutathione (tGSH) levels, and for gene expression analyses of IL-1ß. The kidney tissues were histopathologically evaluated. Statistical analyses of the data were performed using one-way analysis of variance (ANOVA). RESULTS: The administration of cisplatin (the Cis group) yielded a higher level of MDA (4.75 ±0.25 nmol/mL; p < 0.001) and lower levels of tGSH (1.80 ±0.35 mg/L; p < 0.001) compared to other groups. Cisplatin also increased IL-1ß gene expression (6.33 ±0.27 gene expression levels; p < 0.001) compared to other groups. The impact of anakinra on the MDA and tGSH levels, and on IL-1ß gene expression induced by cisplatin was observed as a reversal of these findings (p < 0.05). Anakinra better prevented an increase of the levels of MDA and IL-1ß at a dose of 100 mg/kg compared to a 50 mg/kg dose. CONCLUSIONS: Anakinra prevents oxidative kidney damage induced by cisplatin, in a dose-dependent manner. This result suggests that anakinra may be useful in the treatment of cisplatin-induced kidney damage.

Effect of anakinra, an interleukin one beta antagonist, on oxidative testicular damage induced in rats with ischemia reperfusion.

BACKGROUND: It has been reported in the literature that proinflammatory interleukin-1 beta (IL-1ß) is increased in cases of testicular ischemia reperfusion (I/R) damage. This information suggests that anakinra, an IL-1ß antagonist, may be effective in testicular I/R damage. OBJECTIVE: In our study, we investigated the effect of anakinra on testicular I/R damage induced in rats with torsion/detorsion. METHODS: The 50mg/kg anakinra+testicular torsion/detorsion (KTD-50) and 100mg/kg anakinra+testicular torsion/detorsion (KTD-100) groups received an intraperitoneal (i.p.) injection of 50mg/kg and 100mg/kg of anakinra, respectively. In turn, the testicular torsion/detorsion (TTD) and sham operation (SOG) groups received a single dose of distilled water as a solvent 1h before ketamine anaesthesia. After the testes of the TTD, KTD-50 and KTD-100 groups were subjected to torsion and detorsion for 4h each, the rats were killed with a high-dose anaesthesia, and their testicles were removed and evaluated through biochemical, gene expression and histopathological examinations. The results were evaluated in comparison with those of the SOG group. RESULTS: The levels of malondialdehyde (MDA), myeloperoxidase (MPO) and IL-1ß showed significant increases in the TTD group, which underwent torsion/detorsion, compared to the KTD-50, KTD-100 and SOG groups. Conversely, the levels of glutathione (tGSH), glutathione peroxidase (GPO) and glutathione s-transferase (GST) were found to be significantly higher in the KTD-50, KTD-100 and SOG groups than in the TTD group. CONCLUSION: Anakinra at a 100mg/kg dose histologically suppressed better oxidative stress and tunica albuginea, germ cell, seminiferous tubule and interstitial damage in the testicular tissue compared to a 50mg/kg dose. Experimental results indicate that anakinra might be beneficial in the attenuation of testicular I/R damage.

Effect of anakinra, an interleukin one beta antagonist, on oxidative testicular damage induced in rats with ischemia reperfusion / Efecto de la anakinra, que es un antagonista de la interleucina 1 beta en oxidativo daño testicular, inducida en ratas con isquemia reperfusión

It has been reported in the literature that proinflammatory interleukin-1 beta (IL-1β) is increased in cases of testicular ischemia reperfusion (I/R) damage. This information suggests that anakinra, an IL-1β antagonist, may be effective in testicular I/R damage. Objective: In our study, we investigated the effect of anakinra on testicular I/R damage induced in rats with torsion/detorsion. Methods: The 50mg/kg anakinra+testicular torsion/detorsion (KTD-50) and 100mg/kg anakinra+testicular torsion/detorsion (KTD-100) groups received an intraperitoneal (i.p.) injection of 50mg/kg and 100mg/kg of anakinra, respectively. In turn, the testicular torsion/detorsion (TTD) and sham operation (SOG) groups received a single dose of distilled water as a solvent 1h before ketamine anaesthesia. After the testes of the TTD, KTD-50 and KTD-100 groups were subjected to torsion and detorsion for 4h each, the rats were killed with a high-dose anaesthesia, and their testicles were removed and evaluated through biochemical, gene expression and histopathological examinations. The results were evaluated in comparison with those of the SOG group. Results: The levels of malondialdehyde (MDA), myeloperoxidase (MPO) and IL-1β showed significant increases in the TTD group, which underwent torsion/detorsion, compared to the KTD-50, KTD-100 and SOG groups. Conversely, the levels of glutathione (tGSH), glutathione peroxidase (GPO) and glutathione s-transferase (GST) were found to be significantly higher in the KTD-50, KTD-100 and SOG groups than in the TTD group. Conclusion: Anakinra at a 100mg/kg dose histologically suppressed better oxidative stress and tunica albuginea, germ cell, seminiferous tubule and interstitial damage in the testicular tissue compared to a 50mg/kg dose. Experimental results indicate that anakinra might be beneficial in the attenuation of testicular I/R damage

Antecedentes: Se ha reportado en la literatura que citoquinas interleuquina-1 beta (IL-1β) es mayor en el daño de la isquemia reperfusión testicular (I/R). Esta información sugiere que la anakinra, que es un antagonista IL-1β puede ser eficaz en daño testicular I/R. Objetivo: En nuestro estudio se investigó el efecto de este medicamento en daño testicular I/R inducida en ratas con detorsion/torsión. Métodos: KTD-50 grupo recibido intraperitonealmente (i.p.) inyección de 50mg/kg y KTD-100 Grupo 100mg/kg de anakinra, mientras TTD (control) y SOG (sham grupo operación) recibieron una dosis única de agua destilada como solvente, una hora antes de ketamina anestesia. Después de que los testículos de TTD, KTD-50 y KTD-100 grupos fueron sometidas a torsión y detorsion para cuatro por cuatro horas, las ratas fueron asesinados con altas dosis de anestesia, sus testículos fueron extraídos y evaluados a través de la expresión génica, bioquímicas e histopatológicas de exámenes. Los resultados fueron evaluado en comparación con la de SCG grupo. Resultados: Los niveles de MDA, MPO y IL- 1β mostraron incrementos significativos en el grupo TTD/torsión detorsion administrados frente a-50, KTD KTD-100 y SOG grupos. Por el contrario, los niveles de tGSH, GPO y GST resultaron significativamente más altas en KTD-50 KTD-100 y grupos SOG de TTD en grupo. Conclusión: La anakinra en 100mg/kg dosis mejor histológicamente suprime el estrés oxidativo y la túnica albuginea, células germinales, túbulos seminíferos apretadamente enrollados intersticial y daño en el tejido testicular en comparación con la dosis de 50mg/kg. Los resultados experimentales indican que la anakinra puede ser beneficiosa en la atenuación de los daños I/R testicular

Protective effects of Rutin against methanol induced acute toxic optic neuropathy: an experimental study.

AIM: To determine the effects of Rutin on methanol induced optic neuropathy and compare the results with the effects of ethanol. METHODS: Totally 30 rats were divided into 5 groups, with 6 rats in each group as follows: healthy controls (C), methotrexate (MTX), methotrexate+methanol (MTM), methotrexate+methanol+ethanol (MTME) and methotrexate+ methanol+Rutin (MTMR). In all rabbits except those of the control group, MTX, diluted in sterile serum physiologic, 0.3 mg/kg per oral was applied for 7d by the aid of a tube. After this procedure to the rats of MTM, MTME and MTMR groups, 20% methanol with a dose of 3 g/kg per oral was given by the aid of a tube. In MTME group, 4h after the application of methanol, 20% ethanol was applied by the same way with a dose of 0.5 g/kg. On the other hand, in MTMR group 4h after the application of methanol, Rutin, which was dissolved in distilled water, was applied by the same way with a dose of 50 mg/kg. RESULTS: There were statistically significant differences in tissue 8-hydroxy-2 deoxyguanine (8-OHdG), interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), myeloperoxidase (MPO). glutathione peroxidase (tGSH) and superoxide dismutase (SOD) levels between groups (P<0.001). In MTMR group tissue 8-OHdG, IL-1ß, MDA, and MPO levels were similar with the healthy controls but significantly different than the other groups. In histopathological evaluations, in MTX group there was moderate focal destruction, hemorrhage and decrease in number of astrocytes and oligodendrocytes; in MTM group there was severe destruction and edema with decrease in number of astrocytes and oligodendrocytes; in MTME group there was mild hemorrhage, mild edema, mildly dilated blood vessels with congestion while in MTMR group, optic nerve tissue was resembling the healthy controls. CONCLUSION: Rutin may prevent methanol-induced optic neuropathy via anti-inflammatory effects and decreasing the oxidative stress. New treatment options are warranted in this disease to avoid loss of vision in patients.

The effect of metyrosine on oxidative gastric damage induced by ischemia/reperfusion in rats. Biochemical and histopathological evaluation.

PURPOSE: To investigate the effect of metyrosine against I/R induced gastric damage in rats. METHODS: Eighteen albino Wistar male rats were divided into groups; gastric I/R (GIR), 50 mg/kg metyrosine+gastric I/R (MGIR), and sham (SG) groups. 50 mg/kg metyrosine was given to the MGIR group, and distilled water was given to the GIR and SG groups by the oral gavage. After 30 minutes, 25 mg/kg thiopental sodium was injected intraperitoneally. Ischemia was achieved for 1 hour by clamping the celiac artery of the MGIR and GIR groups, then reperfusion was achieved for 3 hours. After that, animals were killed with 50 mg/kg thiopental. Biochemical and histopathological examinations performed on the gastric tissues. RESULTS: Metyrosine decreased the MDA and MPO and the increased the tGSH and SOD. In addition, it reduced inflammation by suppressing the decrease of COX-1 and the increase of COX-2. Histopathologically, metyrosine decreased symptoms caused by I/R such as mucosal necrosis, hemorrhage, edema, PMNL infiltration, and dilated congested blood vessels. CONCLUSIONS: Metyrosine prevented the I/R induced oxidative stress in the gastric tissue. Metyrosine may be beneficial for gastric I/R injury.

The effect of metyrosine on oxidative gastric damage induced by ischemia/reperfusion in rats. Biochemical and histopathological evaluation

Abstract Purpose: To investigate the effect of metyrosine against I/R induced gastric damage in rats. Methods: Eighteen albino Wistar male rats were divided into groups; gastric I/R (GIR), 50 mg/kg metyrosine+gastric I/R (MGIR), and sham (SG) groups. 50 mg/kg metyrosine was given to the MGIR group, and distilled water was given to the GIR and SG groups by the oral gavage. After 30 minutes, 25 mg/kg thiopental sodium was injected intraperitoneally. Ischemia was achieved for 1 hour by clamping the celiac artery of the MGIR and GIR groups, then reperfusion was achieved for 3 hours. After that, animals were killed with 50 mg/kg thiopental. Biochemical and histopathological examinations performed on the gastric tissues. Results: Metyrosine decreased the MDA and MPO and the increased the tGSH and SOD. In addition, it reduced inflammation by suppressing the decrease of COX-1 and the increase of COX-2. Histopathologically, metyrosine decreased symptoms caused by I/R such as mucosal necrosis, hemorrhage, edema, PMNL infiltration, and dilated congested blood vessels. Conclusions: Metyrosine prevented the I/R induced oxidative stress in the gastric tissue. Metyrosine may be beneficial for gastric I/R injury.

The effect of thiamine and its metabolites on peripheral neuropathic pain induced by cisplatin in rats.

Thiamine pyrophosphate (TPP) is the active metabolite of thiamine. This study aimed to investigate the effects of thiamine and TPP on cisplatin-induced peripheral neuropathic pain (PNP). Male albino Wistar type Rattus norvegicus were divided into six groups (n=6) that received 2 mg/kg cisplatin (CIS), 25 mg/kg thiamine (TM), 2 mg/kg cisplatin+25 mg/kg thiamine (CTM), 25 mg/kg TPP (TPP), 2 mg/kg cisplatin+25 mg/kg TPP (CTPP), or distilled water (healthy group; HG) for 8 days intraperitoneally. Analgesic effect was measured with a Basile Algesimeter. IL-1ß, malondialdehyde (MDA), total glutathione (tGSH), thiamine, and TPP were determined in blood samples. Histopathological examinations were performed on removed sciatic nerves. The percent analgesic effects of the CTM and CTPP groups were calculated to be 21.3% and 82.9%, respectively. Increased production of IL-1ß and MDA by cisplatin was inhibited by TPP, while it was not inhibited by thiamine. Conversion of thiamine to TPP significantly decreased in the CIS group. Histopathological and biochemical investigations demonstrated that hyperalgesia and sciatic nerve damage developed in the CIS and CTM groups with low TPP levels. These results indicate that cisplatin inhibits the formation of TPP from thiamine, leading to severe PNP. This finding suggests that TPP may be more beneficial than thiamine for the treatment of cisplatin-induced PNP.

Effect of etoricoxib on experimental oxidative testicular ischemia-reperfusion damage in rats induced with torsion-detorsion.

Etoricoxib features antioxidant and anti-inflammatory properties concomitantly, suggesting that it may be beneficial in testicular ischemia reperfusion (I/R) damage. Our aim is to investigate the effects of etoricoxib on testicular I/R damage induced with torsion-detorsion (TD). The etoricoxib + torsion-detorsion (ETD) groups of animals were given etoricoxib in 50 and 100 mg/kg of body weight (ETD-50 and ETD-100), while the testes torsion-detorsion (TTD) and sham operation rat group (SOG) animals were given single oral doses of distilled water as a solvent. TTD, ETD-50 and ETD-100 groups were subjected to 720° degrees torsion for four hours, and detorsion for four hours. The SOG group was not subjected to this procedure. Biochemical, gene expression and histopathological analyses were carried out on the testicular tissues. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) were significantly higher, and the levels of total glutathione (tGSH) and glutathione reductase (GSHRd) were significantly lower in the TTD group, compared to the ETD-50, ETD-100 and SOG groups. Etoricoxib at a dose of 100 mg/kg better prevented I/R damage than the 50 mg/kg dose. Etoricoxib may be useful in clinical practice in the reduction of I/R damage on testes caused by torsion-detorsion.

Necl 4 and RNase 5 Are Important Biomarkers for Gastric and Colon Adenocarcinomas.

BACKGROUND There is a need to identify new prognostic factors that may be used in addition to the known risk factors in gastrointestinal adenocarcinomas. In this study, we aimed to determine the expression of Necl 4 and RNase 5 biomarkers in gastric and colon adenocarcinomas, as well as the prognostic efficacy of these biomarkers in gastric and colon adenocarcinomas. MATERIAL AND METHODS Ninety-two cases resected due to stomach and colon adenocarcinoma were included in the study. The expression of Necl 4 and RNase 5 biomarkers was evaluated by immunohistochemical staining of the stomach and colon normal mucosa and adenocarcinoma areas. RESULTS In colon adenocarcinomas, there was a significant association between Necl 4 and lymphovascular invasion, vascular invasion, and perineural invasion (p<0.05). There was a significant association between RNase 5 and histological differentiation in colon adenocarcinomas (p<0.05). There was no association between RNase 5 and Necl 4 in gastric or colon adenocarcinomas. CONCLUSIONS Necl 4 may have prognostic value in colon adenocarcinomas, but it is difficult to ascertain in gastric adenocarcinomas.

Effect of Hippophae rhamnoides Extract on Oxidative Oropharyngeal Mucosal Damage Induced in Rats Using Methotrexate.

OBJECTIVES: The objective of this study is to investigate and evaluate the effect of Hippophae rhamnoides extract (HRE) on oropharyngeal mucositis induced in rats with methotrexate (MTX) through biochemical, gene expression, and histopathological examinations. METHODS: Experimental animals were divided into a healthy group (HG), a HRE+MTX (HREM) group, HRE group (HREG), and a control group that received MTX (MTXG). The HREM and HREG groups of rats was administered 50 mg/kg HRE, while the MTXG and HG groups were given an equal volume distilled water with gavage. Then, the HREM and MTXG rat groups were given oral MTX at a dose of 5 mg/kg 1 hour after HRE and distilled water was administered. This procedure was repeated for 1 month. At the end of this period, all of the animals were sacrificed with a high dose of anesthesia. Then, the amounts of malondialdehyde (MDA) and total glutathione (tGSH) were determined in the removed oropharyngeal tissues. Interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) gene expressions were measured, and all the tissues were studied histopathologically. RESULTS: The amount of MDA was significantly increased in the MTXG group compared to the HREM, HREG, and HG groups (P<0.001). MTX significantly decreased the amount of tGSH in the MTXG group compared to the HREM, HREG, and HG groups (P<0.001). In this study, there were no visible ulcers in the animal group in which the levels of MDA, IL-1ß, and TNF-α were high and the level of tGSH was low. However, histopathologic examination revealed mucin pools in wide areas due to ruptured oropharynx glands, and proliferated, dilated, and congested blood vessels and dilated ductal structures in some areas. CONCLUSION: HRE protected oropharyngeal oxidative damage induced by MTX. As an inexpensive and natural product, HRE has important advantages in the prevention of oropharyngeal damage induced by MTX.

The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate.

OBJECTIVE:: To investigate the effect of HRE (Hippophae rhamnoides extract) on oral mucositis induced in rats with MTX. MATERIAL AND METHODS:: Experimental animals were divided into groups as healthy (HG), HRE+MTX (HMTX), and control group, which received MTX (MTXC). HMTX group received 50 mg/kg HRE while MTXC and HG groups received equivolume distilled water with gavage once a day. After one hour of HRE and distilled water administration, HMTX and MTXC groups received a single dose of oral MTX 5 mg/ kg. This procedure was repeated for one month. RESULTS:: The levels of MDA, IL-1ß, and TNF-α were found to be significantly higher in the cheek, lower lip, and tongue tissue of the animals receiving MTX, compared with HG and HMTX groups; however, these parameters were lower in the cheek and low lip tissue, and a milder damage ocurred in these tissues, compared with the tongue tissue in MTXC group. No histopathologic damage was observed in the cheek, lower lip, and tongue tissues of the rats treated with HRE. CONCLUSION:: This findings indicate that HRE as a natural product is an important advantage compared with synthetic drugs for prophylaxis of oral mucositis developed due to MTX.