Halis Suleyman

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.

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 effect of thiamine pyrophosphate on ethambutol-induced ocular toxicity

Abstract Context: Ethambutol-induced retinal oxidative damage in patients with tuberculosis is still not being adequately treated. The protective effect of thiamine pyrophosphate against oxidative damage in some tissues has been reported, but no information on the protective effects of thiamine pyrophosphate against ethambutol-induced oxidative retinal damage has been found in the medical literature. Objective: The objective is to investigate whether thiamine pyrophosphate has a protective effect against oxidative retinal damage in rats induced by ethambutol. Materials and methods: Experimental animals divided into four groups (n = 10): the healthy group (HG), the ethambutol control group (EMB), thiamine + ethambutol group (Thi–EMB) and thiamine pyrophosphate + ethambutol group (TPP–EMB). The rats in the TPP–EMB and Thi–EMB groups were administered thiamine pyrophosphate and thiamine, respectively, at doses of 20 mg/kg intraperitoneally. Distilled water was administered intraperitoneally to the HG and the EMB groups as a solvent in the same volumes. One hour after drug injection, 30 mg/kg ethambutol was administered via an oral gavage to the TPP–EMB, Thi–EMB and EMB groups. This procedure was repeated once a day for 90 days. At the end of this period, all rats were euthanized under high-dose thiopental sodium anesthesia, and biochemical and histopathological investigations of the retinal tissue were performed. Results: Malondialdehyde (MDA) and DNA damage product 8-hydroxyguanine levels were significantly lower in the retinal tissue of TPP–EMB and HG groups compared to those of the Thi–EMB and EMB groups, and total glutathione (tGSH) was also found to be higher. In addition, severe retinal tissue vascularization, edema and loss of ganglion cells were observed in the Thi–EMB and EMB groups, whereas histopathological findings for the TPP–EMB group were observed to be close to normal. Discussion and conclusion: These findings suggest that thiamine pyrophosphate protects retinal tissues from ethambutol-induced oxidative damage, and thiamine does not. This positive effect of thiamine pyrophosphate may be useful in the prevention of ocular toxicity that occurs during ethambutol use.

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 cisplatin-induced retinal injury: an experimental study

Abstract Aim: Lutein is one of the most common carotenoids defined in human plasma as having potent anti-oxidant effects. We aimed to determine the biochemical and histopathological effects of lutein on cisplatin-induced oxidative retinal injury in rats. Materials and methods: Twenty-four rats were equally divided into four groups as healthy controls (HC group), only cisplatin (5 mg/kg) administered group (CIS group), Lutein (0.5 mg/kg) + cisplatin (5 mg/kg) administered group (LC group), and only Lutein (0.5 mg/kg) (LUT group) administered group. From the blood samples obtained, serum malondialdehyde (MDA), total glutathione (tGSH), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) levels were investigated. In histopathological analyses, the total retinal thickness, retinal pigment epithelium (RPE), photoreceptor layer (PL), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL) were evaluated. Results: MDA, IL-1β, and TNF-a levels were statistically significantly higher (p < 0.001) in CIS group compared with other three groups while tGSH levels were statistically significantly lower (p < 0.001). In subgroup analyses, there was no any statistically significant difference regarding all four parameters analyzed between HC, LC, and LUT groups. In histopathological analyses, cisplatin-induced retinal damage included atrophy and disorganization on outer segment, degeneration and detachment of RPE and PL from choroid, degeneration and edema of INL and IPL, total degeneration of GCL; while cisplatin-induced retinal damage was determined to be significantly prevented with 0.5 mg lutein treatment on histopathological evaluations. Conclusions: Lutein co-administration was highly effective in prevention of cisplatin-induced retinal damage due to the anti-oxidant and anti-inflammatory effects of lutein.

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.

Effect of thiamine pyrophosphate on retinopathy induced by hyperglycemia in rats: A biochemical and pathological evaluation

Purpose: Information is lacking on the protective effects of thiamine pyrophosphate (TPP) against hyperglycemia-induced retinopathy in rats. This study investigated the biochemical and histopathological aspects of the effect of TPP on hyperglycemia-induced retinopathy induced by alloxan in rats. Materials and Methods: The rats were separated into a diabetic TPP-administered group (DTPG), a diabetes control group (DCG) and a healthy group (HG). While the DTPG was given TPP, the DCG and HG were administered distilled water as a solvent at the same concentrations. This procedure was repeated daily for 3 months. At the end of this period, all of the rats were euthanized under thiopental sodium anesthesia, and biochemical and histopathological analyses of the ocular retinal tissues were performed. The results of the DTPG were compared with those of the DCG and HG. Results: TPP prevented hyperglycemia by increasing the amount of malondialdehyde and decreasing endogen antioxidants, including total glutathione, glutathione reductase, glutathione S-transferase and superoxide dismutase. In addition, the amounts of the DNA oxidation product 8-hydroxyguanine were significantly lower in the retinas of the DTPG compared to the DCG. In the retinas of the DCG, there was a marked increase in vascular structures and congestion, in addition to edema. In contrast, little vascularization and edema were observed in the DTPG, and there was no congestion. The results suggest that TPP significantly reduced the degree of hyperglycemia-induced retinopathy. Conclusions: The results of this study indicate that TPP may be useful for prophylaxis against diabetic retinopathy.

Investigation of mucus obtained from different fish species on the acute pain induced with scalpel incision in paw of rats

No comparative study could be found for the analgesic activity of mucuses from the Oncorhynchus mykiss (OM), Salvelinus fontinalis (SF), Salmo coruhensis (SC), Acipenser gueldenstaedtii (AG), and Acipenser baerii (AB) fish species in the literature. We aimed to investigate the effects of mucuses obtained from the abovementioned fish species on scalpel incision-induced pain in the rat paw and to examine the role of oxidant/antioxidant parameters and COX-2 gene expression in the analgesic activities. Animals were divided into groups: SIC (scalpel incision; SI), SIDS (SI+25 mg/kg diclofenac sodium), SOM (SI+25 mg/kg OM mucus), SFM (SI+25 mg/kg SF mucus), SCM (SI+25 mg/kg SC mucus), SAgM (SI+25 mg/kg AG mucus), SAbM (SI+25 mg/kg AB mucus), and HG (healthy). The paw pain thresholds were measured with a Basile algesimeter before and after diclofenac sodium (DS) or mucus administration, and then the rats were euthanized with thiopental sodium. Oxidant/antioxidant and COX-2 gene expression parameters were measured in paw tissues. OM, SC, AG, and AB fish mucuses could not decrease the SI-induced pain. However, SF fish mucus prevented this pain by 69% after the first hour and by 58.3% after the third hour. DS was shown to suppress pain more weakly than SF, preventing the pain by 62.1% and 50.0% after the first and third hours, respectively. SF mucus and DS significantly inhibited increase of COX-2 gene expression, while other fish mucuses could not. None of the fish mucuses except SF mucus in conjunction with DS could significantly inhibit the increase in oxidant parameters and decrease in antioxidants. SF fish mucus should be comparatively assessed in clinical practice for treatment of postoperative pain.