The role of Hippophae rhamnoides L. on 5-fluorouracil-induced oral mucositis in rats.

Current study aimed to research the effect of Hippophae rhamnoides (HRE) on potantial oral oxidative and inflammatory damage of 5-FU in rats. The rats were assigned to three groups; healthy (HG), 5-FU 100mg/kg (FUG) and HRE 50mg/kg +5-FU 100mg/kg (HRFU). The 5-FU was injected in the FUG group intraperitoneally. The HRFU was injected 5-FU at 100mg/kg IP one hour after the 50mg/kg HRE was given orally. Olive oil was used as a solvent for the HG. HRE was given to the rats three times a day for ten days. 5-FU was given one dose on the 1st, 3rd and 5th days. On the 10th day, the tissues removed from the animals were euthanized with high-dose anaesthesia and were macroscopically examined. The levels of the oxidant, antioxidant and proinflammatory cytokines were investigated.It was seen that HRE alleviated the symptoms of severe mucositis by antagonizing the effects of 5-FU on oxidant, antioxidant and proinflammatory cytokines such as malondialdehyde, total glutathione, superoxide dismutase, catalase, nuclear factor kappa-B and interleukin-6 in inner cheek and tongue tissue. These results recommend that HRE may be benefical in the cure of 5-FU-associated oral mucositis.

Effect of felodipine on indomethacin-induced gastric ulcers in rats.

Felodipine is a calcium channel blocker with antioxidant and anti-inflammatory properties. Researchers have stated that oxidative stress and inflammation also play a role in the pathophysiology of gastric ulcers caused by nonsteroidal anti-inflammatory drugs. The aim of this study was to investigate the antiulcer effect of felodipine on indomethacin-induced gastric ulcers in Wistar rats and compare it with that of famotidine. The antiulcer activities of felodipine (5 mg/kg) and famotidine were investigated biochemically and macroscopically in animals treated with felodipine (5 mg/kg) and famotidine in combination with indomethacin. The results were compared with those of the healthy control group and the group administered indomethacin alone. It was observed that felodipine suppressed the indomethacin-induced malondialdehyde increase (P<0.001); reduced the decrease in total glutathione amount (P<0.001), reduced the decrease superoxide dismutase (P<0.001), and catalase activities (P<0.001); and significantly inhibited ulcers (P<0.001) at the tested dose compared with indomethacin alone. Felodipine at a dose of 5 mg/kg reduced the indomethacin-induced decrease in cyclooxygenase-1 activity (P<0.001) but did not cause a significant reduction in the decrease in cyclooxygenase-2 activity. The antiulcer efficacy of felodipine was demonstrated in this experimental model. These data suggest that felodipine may be useful in the treatment of nonsteroidal anti-inflammatory drug-induced gastric injury.

Pollen and bee bread expressed highest anti-inflammatory activities among bee products in chronic inflammation: an experimental study with cotton pellet granuloma in rats.

Little is known about the effectiveness of bee products on chronic inflammation. In this experimental study, it was aimed to investigate and compare the anti-inflammatory activities of honey, propolis, royal jelly, pollen and bee bread, for the first time in the literature. In the study, 48 Sprague Dawley female albino rats weighing 200 ± 20 g were used and bee products were administered by oral gavage method. Healthy, control, honey, propolis, pollen, royal jelly and bee bread groups were randomized. Chronic inflammation was created by cotton pellet method. For the treatments, 1 g/kg of honey, 300 mg/kg/day of pollen, 100 mg/kg/day of propolis, 500 mg/kg/day of bee bread and 100 mg/kg/day of royal jelly were given for seven days. One week later, cotton pellets were removed, and the pro-inflammatory and anti-inflammatory cytokine levels of the blood samples were measured and compared statistically. It was found that honey, propolis, pollen, bee bread and royal jelly had statistically significant anti-inflammatory activities and significantly reduced pro-inflammatory cytokine levels (p < 0.001). Among the anti-inflammatory cytokines, pollen, bee bread and propolis were found to increase the levels of IL-4, IL-10 and IL-1RA the most. Among the pro-inflammatory cytokines, pollen, bee bread and propolis were the ones that decreased IL-6 and TNF-α levels the most; Pollen, bee bread and honey were found to decrease IL-1ß the most (p < 0.001). It was found that all bee products have significant anti-inflammatory activities. The highest anti-inflammatory activity was found with pollen administration, followed by bee bread and propolis.

Protective Effect of Adenosine Triphosphate against 5-Fluorouracil-Induced Oxidative Ovarian Damage in vivo.

OBJECTIVE: The aim of our study was to analyze the effect of ATP on possible ovarian damage of 5-FU in rats. METHODS: The animals were divided to three groups; healthy group (HG), 5-FU alone group (FUG) and ATP+5-FU administered group (AFU). The ATP 4 mg/kg was injected intraperitoneally (IP) into the AFU group. The same volume of saline (0.9% NaCl) as the solvent was administered intraperitoneally to the HG and FUG groups. One hour after administering ATP and solvent, 5-FU 100 mg/kg was injected intraperitoneally to the animals in the AFU and FUG groups. ATP was administered to the animals once a day for 10 days. On the 1st, 3rd and 5th days of 5-FU, one dose (total of 3 doses) was administered. On day 10, the animals were euthanasia with high-dose anaesthesia and ovarian tissues were removed. The removed ovaries were analyzed biochemically andhistopathological. RESULT: ATP significantly suppressed both the increase in MDA and IL-6 levels, and the decrease in tGSH, SOD and CAT levels. Treatment with ATP significantly suppressed the severe vacuolization and primordial follicle degeneration induced by 5-FU in our study. CONCLUSION: ATP was possible to be useful for the treatment of 5-FU-induced ovarian damage.

Favipiravir-induced inflammatory and hydropic degenerative liver injury in rats.

BACKGROUND: Favipiravir is very effective in the treatment of many viral infections, especially at high doses. It was used at such doses to treat coronavirus disease 2019 (COVID-19) during the pandemic. However, liver damage was reported in patients undergoing such treatment. OBJECTIVES: This study aimed to investigate the effects of low and high doses of favipiravir on the liver of rats, using biochemical and histopathological methods. MATERIAL AND METHODS: Wistar albino rats were allocated to one of 3 groups, namely a healthy group (HG), a 100 mg/kg favipiravir (FAV-100) group and a 400 mg/kg favipiravir (FAV-400) group. Favipiravir was administered orally at 100 mg/kg and 400 mg/kg doses to the FAV-100 (n = 6) and FAV-400 (n = 6) groups, respectively. Distilled water was administered orally (1 mL) using the same method to the HG (n = 6). This procedure was repeated twice a day for 1 week. At the end of this period, the animals were euthanized with a high dose of thiopental anesthesia (50 mg/kg) and their liver tissues were removed. RESULTS: Favipiravir caused an increase in malondialdehyde (MDA), nuclear factor kappa B (NF-κB) and interleukin 6 (IL-6) levels in the liver tissue, as well as elevated alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) levels in the blood. Moreover, favipiravir caused a decrease in total glutathione (tGSH), superoxide dismutase (SOD) and catalase (CAT) levels. In addition, severe edema, lymphocyte infiltration and hydropic degeneration were observed in the liver tissue of the FAV-400. CONCLUSIONS: High-dose favipiravir caused more significant oxidative and inflammatory damage in the liver tissue of rats than low-dose favipiravir.

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.

Beneficial interaction of pycnogenol with indomethacin in rats.

Cyclooxygenase 2 (COX-2) is responsible for the therapeutic effects of indomethacin, while inhibition of the COX-1 enzyme and oxidative stress are responsible for its gastro-toxic effects. It has been reported that pycnogenol increases the expression of COX-1, suppresses the expression rate of COX-2 and oxidative stress. Our aim in this study is to investigate the antiinflammatory activities of indomethacin, pycnogenol, and their combination (PI) in rats and to examine their effects on stomach tissue. In the study, anti-inflammatory activity was investigated in carrageenan-induced inflammatory paw edema in albino Wistar male rats. Effects on stomach tissue were performed by applying the previous method. PI, indomethacin and pycnogenol were the best suppressors of carrageenan inflammation and oxidative stress in paw tissue, respectively. While the groups with the lowest COX-1 activity in paw tissue were IC, PIC and PC, respectively, PIC, IC and PC were the ones that best inhibited the increase in COX-2 activity. Pycnogenol inhibited the increase of malondialdehyde, the decrease of total glutathione and COX-1 in the stomach, and significantly suppressed the formation of indomethacin ulcers. Our experimental results showed that pycnogenol reduced the toxic effect of indomethacin on the stomach and increased anti-inflammatory activity. This beneficial interaction of pycnogenol and indomethacin suggests that PI will provide superior success in the treatment of inflammatory diseases.

Ethanol Extract of Myrtle (Myrtus communis L.) Berries as a Remedy for Streptozotocin-Induced Oxidative Stress in Rats.

Streptozotocin (STZ) is an antitumor antibiotic indicating in the treatment of metastatic islet cell carcinoma of the pancreas. It is also used as a tool to create experimental diabetes models. The STZ exposure at a high dose causes severe damage to cells of humans and other mammals. The goal of the present study was to assess the protective effects of the ethanol extract of the Myrtle (Myrtus communis L.) berries, which is a well-known medicinal plant due to its rich phenolic content and beneficial effects on health, against STZ-induced oxidative stress in the diabetic rats.Diabetes was induced by STZ (40 mg/kg, i.p.) in the rats. After diabetes induction, a significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), and blood glucose levels as well as a significant decrease in superoxide dismutase (SOD) activities and glutathione (GSH) levels was observed. The rats were treated to three different ethanol extracts of Myrtle berries (0.25, 0.5, and 1 g/kg) by oral gavage for 14 days. At the end of the experiment, ALT, AST, MDA, and blood glucose levels of the rats significantly decreased while significant increases in GSH levels and SOD activities were observed.We believe that our findings may contribute to the development of new drugs in the treatment of many global disorders due to the antioxidant activity of the ethanol extract of Myrtus communis L. berries.

The relationship of telmisartan with sclerostin in the osteoporosis model induced by ovariectomy in rats.

OBJECTIVES: Our aim is to explain the relationship between Ang II and Scl in osteoporotic (OP) rats and the contribution of Scl in the antiosteoporotic effect mechanism of angiotensin receptor blockers (ARB). METHODS: This study consists of two sub-studies conducted on 4th and 12th weeks after ovariectomy. In study 1, treatment was started immediately after bilateral ovariectomy (OVX), while, in study 2, treatment was started 2 months after OVX. Two different doses of telmisartan (5 and 10 mg/kg) were administered with the aid of gavage for 30 days in both sub-study groups. RESULTS: Serum and tissue Scl, osteocalcin, osteopontin and tartrate-resistant acid phosphatase mRNA expressions were higher and bone mineral densities (BMD) and bone-specific alkaline phosphatase (BALP) mRNA expressions were found to be lower in the OVX groups compared with the sham group. In OVX groups where two different doses of telmisartan were administered, BMD and BALP mRNA expressions increased and serum and tissue Scl decreased. CONCLUSION: There may be a close relationship between angiotensin II and sclerostin in the development of osteoporosis. In this study, telmisartan administration showed an antiosteoporotic effect and significantly decreased the level of sclerostin. These results strongly support this relationship.

The effect of dexmedetomidine on gastric ischemia reperfusion injury in rats. Biochemical and histopathological evaluation.

PURPOSE: To evaluate the protective effect of dexmedetomidine on gastric injury induced by ischemia reperfusion (I/R) in rats. METHODS: A total of 18 male albino Wistar rats were divided groups as: gastric ischemia reperfusion (GIR), gastric ischemia reperfusion and 50 µg/kg dexmedetomidine (DGIR) and sham operation (HG) group. After the third hour of reperfusion, the biochemical and histopathological examinations were performed on the removed stomach tissue. RESULTS: Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were found to be significantly higher in GIR compared to HG (p < 0.05). A statistically significant decrease was observed at the DGIR compared to the GIR for oxidants levels. Total glutathione (tGSH) and superoxide dismutase (SOD) levels were statistically significantly decreased at the GIR, and antioxidants levels were found to be significantly higher in the DGIR (p < 0.05) There was no significant difference between HG and DGIR in terms of SOD (p = 0.097). The DGIRs' epitheliums, glands and vascular structures were close to normal histological formation. CONCLUSIONS: Dexmedetomidine is found to prevent oxidative damage on the stomach by increasing the antioxidant effect. These results indicate that dexmedetomidine may be useful in the treatment of ischemia-reperfusion-related gastric damage.

Biochemical Research of the Effects of Essential Oil Obtained from the Fruit of Myrtus communis L. on Cell Damage Associated with Lipopolysaccharide-Induced Endotoxemia in a Human Umbilical Cord Vein Endothelial Cells.

The aim of this study to investigate the potential effects of essential oils and compounds obtained from MC fruit on sepsis induced endothelial cell damage in human umbilical cord vein endothelial cells (HUVECs) at molecular and cellular levels on in vitro sepsis model. A sepsis model was induced by the application of LPS. The HUVEC treatment groups were as follows: control, LPS, MC, MC plus LPS, 1.8 cineole, 1.8 cineole plus LPS, α-pinene, α-pinene plus LPS, α-terpineol, and α-terpineol plus LPS. Following the treatments, cell proliferation was analyzed using the xCELLigence® system. The mRNA expression of various cytokines [tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), and IL-6] and endothelial nitric oxide (eNOS) were determined by quantitative polymerase chain reaction (qPCR) analysis. The 1.8 cineole and α-pinene treatments at specific doses showed toxic effects on α-terpineine, although it did not result in a change in the cellular index as compared with that of the control group. The application of LPS to HUVECs led to a significant decrease in the cellular index, depending on the treatment time. It did not correct the decreased cell index of MC plus LPS and α-terpineol plus LPS groups as compared with that of the LPS-only group. The 1.8 cineole plus LPS treatment and α-pinene plus LPS treatment significantly increased the cell index as compared with that of the LPS-only treatment, and the cell index in these groups was closer to that of the control. According to the results of the qPCR analysis, neither the MC-only treatment nor the α-terpineol-only treatment significantly reduced cellular damage caused by LPS-induced increases in TNF-α, IL-1ß, IL-6, and eNOS mRNA expression. However, both the 1.8 cineole treatment and α-pinene treatments significantly decreased TNF-α, IL-1ß, IL-6, and eNOS mRNA expression induced by LPS. Volatile oil obtained from MC fruit and the MC compound α-terpineol had no effect on the decreased cell index and increased cytokine response due to LPS-induced endothelial cell damage. However, 1.8 cineole and α-pinene, other major components of MC fruit, ameliorated LPS-induced damage in HUVECs at cellular and biomolecular levels (TNF-α, IL-1ß, IL-6, and eNOS).

The effect of dexmedetomidine on gastric ischemia reperfusion injury in rats. Biochemical and histopathological evaluation

ABSTRACT Purpose: To evaluate the protective effect of dexmedetomidine on gastric injury induced by ischemia reperfusion (I/R) in rats. Methods: A total of 18 male albino Wistar rats were divided groups as: gastric ischemia reperfusion (GIR), gastric ischemia reperfusion and 50 μg/kg dexmedetomidine (DGIR) and sham operation (HG) group. After the third hour of reperfusion, the biochemical and histopathological examinations were performed on the removed stomach tissue. Results: Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were found to be significantly higher in GIR compared to HG (p < 0.05). A statistically significant decrease was observed at the DGIR compared to the GIR for oxidants levels. Total glutathione (tGSH) and superoxide dismutase (SOD) levels were statistically significantly decreased at the GIR, and antioxidants levels were found to be significantly higher in the DGIR (p < 0.05) There was no significant difference between HG and DGIR in terms of SOD (p = 0.097). The DGIRs' epitheliums, glands and vascular structures were close to normal histological formation. Conclusions: Dexmedetomidine is found to prevent oxidative damage on the stomach by increasing the antioxidant effect. These results indicate that dexmedetomidine may be useful in the treatment of ischemia-reperfusion-related gastric damage.

Effects of Emulsion Formulations of Oleuropein Isolated from Ethanol Extract of Olive Leaf in Diabetic Rats.

This study was designed to investigate the effects of emulsion formulations of oleuropein isolated from ethanol extract of olive leaf in streptozotocin-diabetic rats. The rats were treated with the administration of the emulsion containing oleuropein at a low (150 mg/kg b.wt.) and high (225 mg/kg b.wt.) dose for 30 days. At the end of the study, blood samples were drawn from the heart of the rats to determine blood glucose, alanine transaminase, and aspartate transaminase levels. In addition, their liver tissues were dissected to determine the levels of glutathione and thiobarbituric acid-reactive substances, and superoxide dismutase activity. According to the results for both dose treatments, a statistically significant increase in superoxide dismutase activities and glutathione levels of the treated diabetic rats was observed when compared with those of the diabetic control rats. On the other hand, a statistically significant decrease in the levels of thiobarbituric acid-reactive substances, aspartate transaminase and alanine transaminase of the treated diabetic rats was determined. It should be highlighted that the administrations at the high dose were more effective compared to that of the low dose. Furthermore, a substantial decrease in the blood glucose levels of the diabetic rats exposed to the high dose was observed.

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

The investigation of the protective effects of nimesulide on experimental testicular ischemia-reperfusion injury in rats.

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-1ß (IL-1ß) 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.

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 Impact of Resveratrol on Oxidative Stress Induced by Methotrexate in Rat Ileum Tissue: Evaluation of Biochemical and Histopathological Features and Analysis of Gene Expression.

OBJECTIVE: The aim of this study was to assess the impact of resveratrol (RST) on oxidative stress induced by methotrexate in rat ileum tissue. MATERIALS AND METHODS: Twenty-four rats were divided into 4 groups with 6 in each group. Each rat was orally administered the following every day for 30 days: group 1 (MTXG), methotrexate (MTX; 5 mg/kg); group 2 (RMTXG), MTX (5 mg/kg) plus RST (25 mg/kg/day); group 3 (RSTG), RST alone (25 mg/kg/day), and group 4 (controls), distilled water. After the rats had been sacrified, the ilea were removed for the assessment of malondialdehyde (MDA), total glutathione (tGSH) and glutathione peroxidase (GSH-Px). Gene expression analyses for interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) were also performed. Hematoxylin and eosin-stained paraffin-embedded sections of the ileum were analyzed under a light microscope and the findings were recorded. Statistical analyses of the data were performed using one-way ANOVA. RESULTS: The administration of MTX in group 1 yielded a higher level of MDA (8.33 ± 2.5 µmol/g protein, p < 0.001) and lower levels of tGSH (0.97 ± 0.29 nmol/g protein) and GSH-Px (5.22 ± 0.35 U/g protein, p < 0.001) compared to the other groups. MTX also increased IL-1ß (40.33 ± 5.43 gene expression levels), TNF-α (6.08 ± 0.59) and MPO gene expression (9 ± 1.41) in group 1 compared to the controls (11.33 ± 2.07, 2.15 ± 0.33 and 3.43 ± 0.48, respectively, p < 0.001). The impact of RST on IL-1ß, TNF-α and MPO gene expression induced by MTX was observed as a reversal of these findings (p < 0.05). Severe inflammation, damage to the villus epithelium and crypt necrosis was observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the RMTXG group. CONCLUSION: In this study, ileal damage caused by MTX was inhibited by RST.

Effect of thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat kidney.

OBJECTIVES: The biochemical effects of thiamine pyrophosphate on ischemia-reperfusion (IR) induced oxidative damage and DNA mutation in rat kidney tissue were investigated, and compared to thiamine. MATERIALS AND METHODS: Rats were divided into four groups: renal ischemia-reperfusion (RIR); thiamine pyrophosphate + RIR (TPRIR); thiamine + RIR (TRIR); and sham group (SG). RESULTS: The results of biochemical experiments have shown that malondialdehyde (MDA) levels in rat kidney tissue after TRIR and TPRIR treatment were 7.2 ± 0.5 (P > 0.05) and 3.3 ± 0.3 (P < 0.0001) µmol/g protein, respectively. The MDA levels in the SG rat kidney tissue and in RIR group were 3.6 ± 0.2 (P < 0.0001) and 7.6 ± 0.6 µmol/g protein, respectively. Total glutathione (tGSH) levels in TRIR, TPRIR, SG, and RIR animal groups were 2.2 ± 0.3 (P > 0.05), 5.8 ± 0.4 (P < 0.0001), 6.2 ± 0.2 (P < 0.0001), and 1.7 ± 0.2 nmol/g protein, respectively. In the TRIR, TPRIR, SG, and RIR animal groups; 8-hydroxyguanine (8-OHGua)/Gua levels, which indicate mutagenic DNA, were 1.75 ± 0.12 (P > 0.05), 0.93 ± 0.1 (P < 0.0001), 0.85 ± 0.08 (P < 0.0001), and 1.93 ± 0.24 pmol/L, respectively. CONCLUSIONS: It has been shown that thiamine pyrophosphate prevents increase in mutagenic DNA in IR induced oxidative damage, whereas thiamine does not have this effect.

The effect of mirtazapine on cisplatin-induced oxidative damage and infertility in rat ovaries.

Cisplatin causes infertility due to ovarian toxicity. The toxicity mechanism is unknown, but evidence suggests oxidative stress. In this study, the effect of mirtazapine on cisplatin-induced infertility and oxidative stress in rats was investigated. 64 female rats were divided into 4 groups of 16. Except for the controls that received physiologic saline only, all were administered with cisplatin (5 mg/kg i.p.) and mirtazapine (15 mg/kg p.o.) or mirtazapine (30 mg/kg p.o.) for 10 days. After this period, six rats from each group were randomly selected, and malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), total gluthatione (tGSH), gluthatione peroxidase (GPx), superoxide dismutase (SOD), and 8-hydroxy-2 deoxyguanine (8-OH Gua) levels were measured in their ovarian tissues. Reproductive functions of the remaining rats were examined for 6 months. The MDA, MPO, NO groups and 8-OH Gua levels were higher in the cisplatin-treated groups than the controls, which was not observed in the mirtazapine and cisplatin groups. GSH, GPx, and SOD levels were reduced by cisplatin, which was prevented by mirtazapine. Cisplatin caused infertility by 70%. The infertility rates were, respectively, 40% and 10% for the 15 and 30 mg/kg mirtazapine administered groups. In conclusion, oxidative stress induced by cisplatin in the rat ovary tissue causes infertility in the female rats. Mirtazapine reverses this in a dose-dependent manner.

Urine iodine levels in preeclamptic and normal pregnant women.

The aim of this study was to investigate the urine iodine concentration in women with severe preeclampsia and in healthy women in Erzurum, Turkey. Urine specimens were obtained from 40 severe preeclampsia and 18 healthy pregnant women. Urinary iodine levels were determined by the Foss method based on the Sandell-Kolthoff reaction. The urinary iodine level for women with severe preeclampsia was 4.25 +/- 2.7 microg/dL, lower than 20.89 +/- 6.4 microg/dL of urinary iodine for healthy pregnant women (p < 0.001). Blood magnesium concentration was found to be 1.63 +/- 0.05 mg/dL for women with severe preeclampsia, which is lower than that of healthy pregnant women (1.87 +/- 0.05 mg/dL; p < 0.001). There was a positive correlation between urinary iodine level and blood magnesium level in pregnant women with preeclampsia (Pearson correlation coefficient = 0.43; p < 0.01). However, there was no correlation between urinary iodine level and blood magnesium level in healthy pregnant women. There was no difference in thyroid hormone levels (T4, TSH, FT4) between women with severe preeclampsia and healthy pregnant women. However, there was a difference in T3 thyroid hormone levels between women with severe preeclampsia (1.86 +/- 0.4 microg/dL) and healthy pregnant women (1.45 +/- 0.3 microg/dL; p < 0.001). There was also a difference in FT3 between women with severe preeclampsia (2.77 +/- 0.4 pg/mL) and healthy pregnant women (2.41 +/- 0.5 microg/dL; p < 0.01). Urinary iodine excretion is currently the most convenient laboratory marker of iodine deficiency. The method is useful for the rapid and low-cost assessment of iodine deficiency. Our results suggested that urinary iodine concentration might be a useful marker for prediagnosing preeclamptic women. In addition, iodine supplementation may also be considered for preeclamptic therapy.