Protection against experimental cisplatin-induced optic nerve toxicity using resveratrol: A rat model study.

AIM: To investigate the effects of resveratrol on oxidative stress and inflammation parameters and histological alterations in cisplatin-induced optic nerve damage in a mouse model. MATERIAL AND METHOD: Thirty-six albino Wistar male rats were divided into three groups as control, 5 mg/kg cisplatin-administered (Cis) and 5 mg/kg cisplatin + 25 mg/kg resveratrol-administered (Cis + Res) animals. At the end of the experimental period, the rats were sacrificed with high-dose (50 mg/kg) thiopental sodium, and their optic nerves were dissected. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), total antioxidant status (TAS), tumour necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-KB) levels, and histopathological findings were assessed using the optic nerve tissues. RESULTS: In the Cis + Res group, the MDA, TOS, OSI, TNF-a and NFK-B levels were significantly lower and the tGSH and TAS levels were significantly higher compared with the Cis group (P = 0.001). In histological evaluations, there were dilated and congested blood vessels, destruction, oedema, degeneration, haemorrhage, and proliferating capillaries indicating the presence of inflammation and damage only in the Cis-administered group. However, in the Cis + Res group, the histological findings were very similar to the healthy controls. CONCLUSION: Resveratrol is a promising neuroprotective agent for cisplatin-induced optic nerve toxicity with its anti-oxidant and anti-inflammatory effects. Further investigations are needed to evaluate the possible therapeutic effects on other optic nerve toxicities.

Effect of taxifolin on cisplatin-associated oxidative optic nerve damage in rats.

AIM: To investigate the effect of taxifolin on cisplatin-induced oxidative and proinflammatory optic nerve damage in rats. METHODS: A total of 18 albino Wistar male rats were assigned into 3 groups, as follows; Group 1: Control group, Group 2: Only cisplatin administered group for 14 days (Cisplatin group), and Group 3: Taxifolin + cisplatin administered group for 14 days (CIS + TAX group). Serum malondialdehyde (MDA), total Glutathione (tGSH), Nuclear Factor-Kappa B (NF-ƘB), Total Oxidative Status (TOS) and Total Antioxidant Status (TAS) levels were collected from the left eyes of rats. Rats' right eyes were enucleated for histopathological evaluations of optic nerves. RESULTS: NF-ƘB, MDA and TOS levels were statistically significantly higher (p < 0.001) in cisplatin group when compared to other 2 groups, the tGSH and TAS levels of which were statistically significantly lower (p < 0.001). Regarding these parameters, in cisplatin group NF-ƘB, MDA and TOS levels were statistically significantly increased with cisplatin administration and giving taxifolin concomitantly with cisplatin prevented this elevation. On the other hand, tGSH and TAS levels were statistically significantly decreased with cisplatin administration and routine simultaneous application of taxifolin with cisplatin prevented this decrease. In histopathological findings, haemorrhage was observed in the perineum of the injured optic nerves in the cisplatin treated group. And also edoema and degeneration in nerve fascicles in damaged optic nerves were seen in the cisplatin group. In the taxifolin treated group histopathological examinations were close to normal appearance, except mild edoema in nerve fascicles. CONCLUSION: Cisplatin causes oxidative stress on the rat optic nerves, and these changes lead to significant histopathological damage. Taxifolin, which we used to prevent oxidative damage to the optic nerves caused by cisplatin, has been emphasized as a powerful antioxidant agent in many previous scientific investigations. Concomitant administration of taxifolin may prevent these adverse effects of cisplatin, as well as histopathological damage. Further studies are needed to fully determine the effects of cisplatin and taxifolin on the eye.

The effect of Liv-52 on liver ischemia reperfusion damage in rats.

BACKGROUND: Liver ischemia reperfusion (I/R) damage which is frequently seen in clinical hepatobiliary surgeries has no effective treatment for it. Liv-52, known to have hepatoprotective effects, is a natural antioxidant drug licensed by the Ministry of Health of India. The aim of our study is to investigate the effect of Liv-52 on liver damage induced by I/R in rats. METHODS: Albino Wistar male rats were divided into three groups; liver I/R (IR), 20 mg/kg Liv-52 + liver ischemia reperfusion (LIR) and sham operation applied to control group (HG). Liv-52 was administered to the LIR group (n = 6) 1 h prior to I/R application and distilled water was given orally to IR (n = 6) and HG (n = 6) groups as a solvent. Ischemia was determined as 1 h, and reperfusion was identified as 6 h in animals. RESULTS: Increased levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, malondialdehyde, myeloperoxidase, and decreased levels of superoxide dismutase, and glutathione related enzymes caused by I/R application have been converged to healthy group level with Liv-52 treatment and the damage in liver tissue has been improved histopathologically. CONCLUSIONS: Liv-52 may be beneficial for preventing liver I/R damage in pre-surgery application.

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 resveratrol on oxidative ovary-damage induced by methotrexate in rats (Resveratrol oxidative ovary-damage).

Methotrexate (MTX) is a commonly used folic acid antagonist for the treatment of neoplasia and some autoimmune diseases. Resveratrol has important anti-inflammatory, antioxidant and immunomodulatory properties. The aim of this study was to investigate the effects of resveratrol on MTX-induced ovary-damage and oxidative stress in rats. We hypothesized that supplement of resveratrol could counteract MTX-induced cytotoxicity in rat ovary. Albino Wistar female rats were randomly divided into three groups: Healthy control (HC), resveratrol + methotrexate (RMTX) and methotrexate (MTX) group. Their ovaries were removed. Biochemical and histopathological methods were utilized for evaluation of the oxidative ovary-damage. MDA was found to be higher but tGSH and SOD were lower in the ovarian tissue of the rat group administered MTX, but it is observed that these ratios are reversed in HC and in RMTX groups. MTX treatment induced ovary damage and especially pre-treatment with resveratrol provided protective effect against this MTX-induced ovary-damaged.

Effect of taxifolin on development of retinopathy in alloxan-induced diabetic rats.

Purpose: Diabetic retinopathy (DR) is one of the leading causes of blindness. In DR patients, antioxidant defence is disrupted, and production of reactive oxygen species and pro-inflammatory cytokines such as interleukin 1ß (IL-1ß) and tumour necrosis factor alpha (TNF-α) increases. Taxifolin has been reported to suppress reactive oxygen species, IL-1ß and TNF-α production. The aim of this study is to biochemically and histopathologically examine the protective effect of taxifolin against DR damage induced by alloxan. Materials and methods: Alloxan received rats with a blood glucose level of ≥250 mg/dL were divided into taxifolin-treated (TAX) (n = 6), diabetic control (DC) (n = 6) groups. There were rats received only saline in non-diabetic control (NC) group (n = 6). Taxifolin (50 mg/kg) was orally administered to the TAX group rats. DC and NC rats received the same volume of saline as a solvent. This procedure was repeated once a day for 3 months. At the end of this period, animals were killed by high dose thiopental sodium anaesthesia. Histopathological examinations were then performed on excised rat eyes. Malondialdehyde (MDA), total glutathione (tGSH), IL-1ß and TNF-α levels were measured in obtained blood samples. Results: MDA, IL-1ß and TNF-α levels were significantly increased in blood samples of DC group rats with hyperglycemia induced by alloxan compared with NC group (p < 0.0001), and decreased in the TAX group compared with the DC group (p < 0.0001). The levels of tGSH were significantly decreased in blood samples of DC group rats compared with NC group (p < 0.0001), and increased in the TAX group compared with the DC group (p < 0.0001). Histopathologically, retinal ganglion cells of the TAX group had a slightly dilated and congested blood vessel, and severe damage was inflicted to the retinal ganglion cell layer of the DC group. Conclusions: Experimental results suggest that taxifolin may be beneficial in the treatment of DR.

Effect of lycopene on oxidative ovary-damage induced by cisplatin in rats.

The anti-cancer drugs, particularly those used in reproductive period, may cause several complications such as ovarian insufficiency and infertility. The mechanism of action of cisplatin toxicity on the ovaries is not fully described. However, further production of free oxygen radicals and reduced production of antioxidants are thought to have an effect on the occurrence of cisplatin toxicity. The aim of this study was to investigate the effects of lycopene on cisplatin-induced ovary-damage, oxidative stres and histological changes in rats. Albino Wistar female rats were randomly divided into three groups. The control group (Group 1) received sunflower oil; animals in Group 2 received only cisplatin; one hour of lycopene pre-treatment was applied to the animals in Group 3 before administration of cisplatin. Cisplatin (5 mg/kg/day) was intraperitoneally injected as a single dose and lycopene (0.5 mg/kg/day) was administered by gavage. Biochemical and histopathological methods were utilised for evaluation of the oxidative ovary-damage. There was an increase in the levels of malondialdehyde, while total glutathione, glutathione reductase, and superoxide dismutase were decreased in Group 3, but it is observed that these ratios are reversed in the Group 1 and in the Group 2. Lycopene had protective effect against cisplatin-induced ovary-damaged.

The effects of lycopene on alloxan induced diabetic optic neuropathy.

AIM: To determine the effects of lycopene treatment in prevention of diabetes associated inflammatory response and oxidative stress in an experimental model. With this aim we investigated the levels of oxidative stress markers including Malondialdehyde (MDA), and total oxidative status (TOS)together with inflammatory markers including nuclear factor- kappa B (NFKB) and tumor necrosis factor α (TNF-α) and antioxidants including total glutathione (TGSH), total oxidative status (TOS) and total anti-oxidative status (TAS) levels on eye tissue. MATERIAL AND METHODS: Totally 18 albino Wistar male rats (250-280 grams) assigned into three groups, with six rats in each group as follows: healthy group (HG), control group (CG), and lycopene group (LG). The diabetes was induced with alloxan administration in rats of CG and LG. Lycopene (4 mg/kg) was administered to the rats in LG once a day for 3 months. At the end of this period, the animals were sacrificed and their eyes were enucleated for histopathological evaluations. From the tissues, MDA, GSH, TOS, TAS, TNF-α and NF-κB levels were analyzed. RESULTS: MDA, TOS, OSI, NFKB and TNF-α levels were significantly higher, while TGSH and TAS levels were significantly lower in CG compared with HG (p < 0.001). On the other hand in LG; MDA, TOS, OSI, NFKB and TNF-α levels were significantly lower, while TGSH and TAS levels were significantly higher compared with CG (p < 0.001). Regarding histopathological findings, although there was severe damage on optic nerve of rats in CG; there was only a slight damage in lycopene administered group. CONCLUSION: For the first time in literature we determined that, lycopene was significantly effective in prevention of augmented inflammation and oxidative stress on eye tissue associated with diabetes, as well as the tissue damage on optic nerve. However, studies investigating the long-term clinical effects of lycopene on diabetic individuals are warranted.

The effects of lutein on optic nerve injury induced by ethambutol and isoniazid: an experimental study.

AIM: Ethambutol and isoniazid are two major effective first line agents in tuberculosis treatment having some visual adverse effects. We aimed to determine the protective effects of lutein on oxidative optic neuropathy induced by ethambutol and isoniazid in an experimental model. MATERIAL AND METHOD: Totally 24 albino Wistar male rats were assigned into 4 groups, with 6 rats in each group as follows: healthy controls (HC group), 50 mg/kg ethambutol +50 mg/kg isoniazid administered group (EI), 0.5 mg/kg lutein +50 mg/kg ethambutol +50 mg/kg isoniazid administered group (LEI-05) and only Lutein (0.5 mg/kg) (LUT group) administered group. From the blood samples and tissues obtained from the rats, Malondialdehyde (MDA), total glutathione (GSH), interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) levels were studied. Histopathological evaluations were performed at the end of the study. RESULTS: Serum and tissue IL-1ß, TNF-α and MDA levels were the highest in EI group which were significantly lower in lutein administered group. On the other hand, serum and tissue total GSH levels were the lowest in EI group which were significantly higher in Lutein administered group. In histopathological evaluations, there were significant differences between EI group and all other three groups with edema and hemorrhage in connective tissue covering optic nerve, dilated and congested capillary, decrease in astrocytes and oligodendrocytes. CONCLUSION: Isoniazid and ethambutol induced toxic optic neuropathy although not common, may have some potential devastating effects on vision. Lutein is determined as an effective agent in prevention of isoniazid and ethambutol induced toxic optic neuropathy.

The effect of rutin on cisplatin-induced oxidative cardiac damage in rats.

OBJECTIVE: Cisplatin is an anticancer drug used for treating childhood solid tumors. Symptoms related to cisplatin-induced cardiovascular adverse effects may be mild or severe. Rutin (vitamin P1) has many properties, including as antioxidant, anticancer, antidiabetic, antimicrobial, antiulcer, and tissue renewal properties. Therefore, we aimed to biochemically, histopathologically, and immunohistochemically demonstrate the effect of rutin on cisplatin-induced cardiotoxicity in rats. METHODS: The rats included in our study were divided into four groups: Healthy group (HE), 5-mg/kg cisplatin group (CP), 50 mg/kg rutin+5-mg/kg cisplatin (CR-50), 100-mg/kg rutin+5-mg/kg cisplatin (CR-100) group. RESULTS: CP group administered cisplatin had significantly increased blood, serum, and cardiac tissue malondialdehyde (MDA), interleukin 1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), troponin I, creatine kinase (CK), and CK-MB levels compared to the HE group, whereas there was a significant decrease in the total glutathione (tGSH) levels. Rutin was observed to prevent the increase in MDA, IL-1ß, TNF-α, troponin I, CK, and CK-MB levels as well as prevent the decrease in tGSH levels more significantly when administered at a 100-mg/kg dose than at a 50-mg/kg dose. Histopathologically, cardiac necrosis, dilated/congested blood vessels, hemorrhage, polymorphonuclear leukocyte, edema, and cells with pyknotic nuclei were observed in the CP group. Rutin was shown to prevent cisplatin-induced cardiac damage more effectively when used at a100-mg/kg dose than at a 50-mg/kg dose. CONCLUSION: These results suggest that rutin is useful for preventing cisplatin-related cardiovascular damage.

Effects of Pycnogenol on cisplatin-induced optic nerve injury: an experimental study.

AIM: To determine the effects of Pycnogenol on cisplatin-induced optic nerve damage. MATERIAL AND METHOD: Totally 18 albino Wistar male rats were assigned into three groups, with six rats in each group as follows: healthy controls (HC group), only cisplatin (2.5 mg/kg) administered group (CIS group) and Pycnogenol (40 mg/kg) + cisplatin (2.5 mg/kg) administered group (PYC group). We analyzed the levels of malondialdehyde (MDA) as a marker of lipid peroxidation and oxidative stress, total glutathione (tGSH) as a marker of antioxidant status, nuclear factor-kappa B (NF-κB) and tumor necrosis factor alpha (TNF-α) as inflammatory markers, total oxidative status (TOS) and total antioxidant status (TAS) on eye tissue together with histopathological evaluation of optic nerve in an experimental model. RESULTS: In CIS group MDA, TOS, TNF-α and NF-κB levels were statistically significantly higher (p < 0.001) than HC group while tGSH and TAS levels were significantly lower (p < 0.001). On the other hand, in PYC group MDA, TOS, TNF-α and NF-κB levels were statistically significantly lower (p < 0.001) than CIS group while tGSH and TAS levels were significantly higher (p < 0.001). CONCLUSION: Pycnogenol pretreatment was highly effective in preventing augmentation of cisplatin-induced oxidative stress and inflammation in eye tissue.

The effect of rutin on ovarian ischemia-reperfusion injury in a rat model.

The effect of rutin on ovarian ischemia-reperfusion (I/R) injury was investigated in this experimental study. Eighteen Wistar albino female rats were divided into three groups as follows: I/R group (IRG; n = 6), 50 mg/kg rutin + I/R group (RG; n = 6), and a healthy control group scheduled for a sham operation (SG; n = 6). 2 h of ischemia and following 2 h of reperfusion were created in the IRG and RG by using a torsion model involving atraumatic vascular clips. Rutin, a flavonoid glycoside, was injected intraperitoneally at the dose of 50 mg/kg to RG group 1 h before reperfusion. Then, rats were euthanized and their ovaries were removed for biochemical and histopathological examination and also assessment of the gene expressions. IRG group had a significant increase in malondialdehyde (MDA) levels, in the expressions of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß), and also in the activity of cyclooxygenase 2 (COX-2) unlike the significant decrease in total glutathione (tGSH) levels and the activity of COX-1 when compared to the SG group. However, rutin significantly decreased MDA levels, the expressions of TNF-α and IL-1ß, and also the activity of COX-2 while it increased significantly tGSH levels and the activity of COX-1 in the RG group in comparison with the IRG group. Rutin ameliorated the I/R-induced ovarian injury in rats via its possible antioxidative and anti-inflammatory effects.

The effects of rutin on cisplatin induced oxidative retinal and optic nerve injury: an experimental study.

AIM: To determine the role of rutin in prevention of cisplatin induced retinal and optic nerve injury in an experimental study. MATERIALS AND METHODS: Totally 18 albino Wistar male rats were assigned into three groups, as follows: healthy controls (HC group), only cisplatin administered group for 14 days (CIS group), and rutin + cisplatin administered group for 14 days (RC group). Blood samples were obtained from animals just before the scarification. Serum malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH), superoxide dismutase (SOD), interleukin 1 beta (IL-1ß) and tumour necrosis factor alpha (TNF-α) levels were investigated. The eyes were enucleated for histopathological evaluations of retina and optic nerve. RESULTS: MDA, MPO, IL-1ß and TNF-α levels were statistically significantly higher (p < 0.001) in CIS group compared with other two groups while tGSH and SOD levels were statistically significantly lower (p < 0.001). Regarding these parameters, in CIS group MDA, MPO, IL1ß and TNF-α levels were statistically significantly increased with cisplatin administration and giving rutin concomitantly with cisplatin prevented this increase. On the other hand, tGSH and SOD levels were statistically significantly decreased with cisplatin administration and giving rutin concomitantly with cisplatin prevented this decrease. In qualitative analyses of histopathological findings of retina and optic nerve; the results of RC group were similar with the results of healthy controls; but there was statistically significant differences between CIS group and other two groups (p < 0.001). CONCLUSIONS: Concomitant rutin administration may prevent the detrimental effects of cisplatin on lipid peroxidation, oxidative stress and inflammation markers and may also avert the histopathological damage on retina and optic nerve. Further studies are warranted to determine the effects of cisplatin and rutin on eye.

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.

Protective effect of resveratrol against methotrexate-induced oxidative stress in the small intestinal tissues of rats.

The effect of resveratrol on the damage induced by methotrexate (MTX) in rat duodenum and jejunum tissue was investigated and evaluated in comparison with famotidine. The rats were divided into four groups as healthy group (HG), resveratrol+MTX (RMTX) group, famotidine+MTX (FMTX) group and the control group which received MTX (MTXC). RMTX group was given resveratrol 25 mg/kg and FMTX group famotidin 25 mg/kg, while MTXC and HG groups were orally administered distilled water once a day for 30 days. The rats in RMTX, FMTX and MTXC groups were given MTX of 5 mg/kg dose by the same way for 30 days. At the end of this period, amount of MDA, 8-OH/Gua and tGSH, and MPO gene expression were measured in the duodenal and jejunal tissues and the results were histopathologically evaluated. Resveratrol and famotidine were found to significantly prevent elevation of the MDA, 8-OH/Gua and MPO parameters with MTX and decrease of the levels of tGSH in the duodenal and jejunal tissues. Both drugs prevented severe damage to the villus and crypt epithelium in the duodenum and jejunum, congestion and hemorrhage, inflammatory cell infiltration and necrosis in the mucosa and submucosa due to MTX administration. Resveratrol could be considered in the clinical practice for treatment of the tissue damage in the intestines due to use of MTX, in comparison with famotidine. Resveratrol may be more advantageous than famotidine in long-term use against MTX toxicity since it does not inhibit gastric acid secretion.