Ferda Keskin Cimen

Effect of Kineret® on ovarian ischemia reperfusion injury in a rat model.

To investigate the effect of Kineret® on ischemia reperfusion (IR) injury in rat ovaries.

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

ABSTRACT 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-1β, 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.

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

Abstract 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-1β), 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-1β, 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 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-1β, 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-1β 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.

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

Abstract 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-1β) 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-1β 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, IL1β 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.

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-1β (IL-1β) 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-1β, 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.

Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats

Intestinal mucositis is one of the major problems in the patients receiving cancer treatment. Nimesulide is a drug with antioxidant, antiinflammatory and antiulcer features. We aimed to investigate the effect of nimesulide on the small intestine mucositis induced by methotrexate (MTX) in rats. Experimental animals were divided into the control group, MTX group (MTXG) and nimesulide+MTX administered group (NMTXG) with eight rats per group. The control and MTXG groups were given distilled water by gavage and the NMTXG was given nimesulide 100 mg/kg orally. After one hour, the NMTXG and MTXG rat groups were administered oral MTX 5 mg/kg. This procedure was repeated once a day for 15 days and the rats were sacrificed. The duodenum and jejunum of each rat was removed for the assessment of biochemical markers and histopathological evaluation. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly higher in the duodenal and jejunal tissues of the animals which received MTX, compared to the control and NMTXG (P<0.001). Also, the levels of total glutathione (tGSH), glutathione reductase (GSHRd), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were significantly lower in the MTXG (P<0.001) compared to other groups. MTX led to villus and crypt epithelial damage and inflammation containing marked PMNL and eosinophils in the intestinal tissues histopathologically. Whereas, there was only mild irregularities in the villus structures of the NMTXG. Nimesulide protected the small intestines against damage by MTX. Intestinal mucositis caused by MTX may be preventable by co-administered nimesulide.

The Effects Of Lycopene On Alloxan Induced Diabetic Optic Neuropathy

Abstract 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.

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

Abstract 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 Effects of Lutein on Optic Nerve Injury Induced By Ethambutol and Isoniazid: An Experimental Study

Abstract 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-1β) 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-1β, 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.