The effects of metyrosine on ischemia-reperfusion-induced oxidative ovarian injury in rats: Biochemical and histopathological assessment.

The aim of this study is to investigate the effect of metyrosine on ischemia-reperfusion (I/R) induced ovarian injury in rats in terms of biochemistry and histopathology. Rats were divided into: ovarian I/R (OIR), ovarian I/R+50 mg/kg metyrosine (OIRM) and sham (SG) operations. OIRM group received 50 mg/kg metyrosine one hour before the application of the anesthetic agent, OIR and SG group rats received equal amount of distilled water to be used as a solvent orally through cannula. Following the application of the anesthetic agent, ovaries of OIRM and OIR group rats were subjected to ischemia and reperfusion, each of which took two hours. This biochemical experiment findings revealed high levels of malondialdehyde (MDA) and cyclo-oxygenase-2 (COX-2) and low levels of total glutathione (tGSH), superoxide dismutase (SOD) and cyclo-oxygenase-1 (COX-1) in the ovarian tissue of OIR group, with significant histopathological injury. In metyrosine group, MDA and COX-2 levels were lower than the OIR group whereas tGSH, SOD and COX-1 levels were higher, with slighter histopathological injury. Our experimental findings indicate that metyrosine inhibits oxidative and pro-inflammatory damage associated with ovarian I/R in rats. These findings suggest that metyrosine could be useful in the treatment of ovarian injury associated with I/R.

Effects of putrescine on oxidative stress, spermidine/spermine-N(1)-acetyltransferase, inflammation and energy levels in liver and serum in rats with brain ischemia-reperfusion.

We aimed to examine the effects of brain ischemia-reperfusion (IR) especially on serum parameters or liver enzymes, free radicals, cytokines, oxidatively damaged DNA, spermidine/spermine N-1-acetyltransferase (SSAT). The effects of addition of putrescine on IR will be evaluated in terms of inflammation and oxidant-antioxidant balance in liver.The study was conducted on 46 male Albino Wistar rats weighing 200-250 g. The rats were grouped into: 1-Sham group (n = 6). 2-IR group (n = 8): The carotid arteries were ligated for 30-min and reperfusion was achieved for 30-min under general anesthesia. 3-Ischemia + putrescine + reperfusion group (IPR) (n = 8): Unlike the IR group, a single dose of 250 µmol kg-1 putrescine was given by gavage at the beginning of reperfusion. In putrescine treatment groups in addition to the procedures performed in the IR group a total of 4 doses of 250 µmol kg-1 putrescine were given at 12-h intervals, with the first dose immediately after 30-min reperfusion (4-IR+putrescine group (IR+P1) (n = 8)); 3 h after the 30-min reperfusion (5-IR+putrescine group (IR+P2) (n = 8)); 6 h after the 30-min reperfusion (6-IR+putrescine group (IR+P3) (n = 8)). ALT, AST, ATP, NO, SSAT, 8-OHdG levels were analyzed in the serum, and liver samples. NF-κB and IL-6 levels were analyzed in the liver samples.Brain IR causes inflammatory, oxidative and DNA damage in the liver, and putrescine supplementation through gavage reduces liver damage by showing anti-inflammatory and antioxidant effects.

Role of exogenous putrescine in the status of energy, DNA damage, inflammation, and spermidine/spermine-n(1)- acetyltransferase in brain ischemia-reperfusion in rats.

Objectives: This study aims to investigate the role of putrescine against brain ischemia-reperfusion (IR) injured rats administered with 250 µmol/kg exogenous putrescine and highlight the IR-associated mechanisms in energy metabolism and inflammatory pathway. Materials and Methods: The rats were divided into six groups: 1-Sham group; 2-IR group, 30 min of ischemia and 30 min of reperfusion was performed with bilateral carotid occlusion (BCAO); 3-IPR group, a single oral dose of putrescine was administered at the start of the 30-minute reperfusion; while in the other treatment groups, 4 doses of putrescine were given within 12-hour intervals. After 30 min of reperfusion, the first dose was administered immediately in the IR-PI (group 4), after 3 hr in IR-PII (group 5), and after 6 hr in IR-PIII (group 6). Interleukin-6 (IL-6), Nuclear factor NF-kappa-B (NF-kB), Adenosine triphosphate (ATP), total Nitric oxide (NO), 8-hydroxyguanosine (8-OHdG), Spermidine/Spermin N-acetyltransferase (SSAT) levels were analyzed in brain tissues. Results: IR reduced brain ATP levels; however, putrescine treatment reversed this state. Brain NO and 8-OHdG levels, and NF-kB and IL-6 levels increased significantly in the IR group and these elevations were decreased in putrescine administered groups. SSAT levels were higher in the IR-PII group. The lowest levels were observed in the IR-PIII group. Conclusion: The exogenous putrescine supplementation after cerebral IR creates neuroprotective effects independent of the time of administration; according to conditions such as formation of radicals in the brain, the spread of the inflammation and the need for consumption of energy are considered as a whole.

Evaluation of sialic acid, malondialdehyde and glutathione levels in infertile male.

INTRODUCTION AND OBJECTIVES: Around 15% of productive couples in the world are infertile. Recent years, biochemical mechanisms leads to male infertility are started to research. Redox regulation and oxidative stress (OS) show importance in the pathogenesis of infertility in male. Malondialdehyde (MDA) and Glutathione (GSH) are biochemical indicatives of sperm damage by reactive oxygen species (ROS). In addition, sperm are coated with a thick glycocalyx rich in sialic acids. It is aimed to determine and evaluate the differences between normozoospermic and oligozoospermic individuals according to sialic acid, MDA and GSH concentrations and correlations between spermyogram and these parameters. MATERIAL AND METHODS: This study was carried out on seminal plasma of individuals who admitted to Selcuk University Faculty of Medicine IVF Unit Andrology Laboratory. The groups were divided into two as normozoospermics (n=30, sperm concentration≥15million/mL), and oligozoospermics (n=30, sperm concentration<15million/mL). Spermyogram were evaluated regarding WHO (2010) Kruger criteria. GSH, MDA and sialic acid concentrations were analyzed in seminal plasma. Diagnostic performance of sialic acid has been determined with ROC curve analysis. RESULTS: Sialic acid levels were significantly lower in Normozoospermic than Oligozoospermic individuals (p<0.0001), MDA and GSH levels were not differ significantly in both groups (p>0.05). Sialic acid correlated significantly with most of the spermyogram findings. When diagnostic performance of sialic acid was evaluated, the cut off value of sialic acid found as 4.175nmol/mL by ROC curve. CONCLUSION: High seminal plasma sialic acid levels may be used as a biomarker and sialic acid is important determinant in oligozoospermia.

Can magnesium sulfate prophylaxis reduce colistin nephrotoxicity?

The study aimed to investigate the role of magnesium sulfate prophylaxis in nephrotoxicity caused by colistin. Thirty Wistar Albino rats were divided into four groups: control, colistin, magnesium (Mg), and Mg+colistin. The drugs were administered to the groups for seven days. Urea-creatinine values were measured at the beginning (T0) and end (T1) of the study. Malondialdehyde (MDA) levels were measured in plasma and kidney tissue, glutathione (GSH) levels were analyzed in the erythrocyte and kidney tissues. At the end of the study, the semiquantitative score (SQS) was calculated by the histopathological examination of the kidneys. Urea values significantly decreased in Mg and Mg+colistin groups compared to the baseline (p=0.013 and p=0.001). At the time of T1, these groups had significantly lower urea values than the colistin and control groups. Creatinine value was significantly increased in the colistin group compared to baseline (p=0.005), the creatinine value in the colistin group was significantly higher than the Mg+colistin group (p=0.011). Plasma MDA levels were significantly higher in the colistin group compared to the other groups at the time of T1 (p<0.001). The Mg+colistin group had lower renal MDA levels than the colistin group. The colistin group had significantly higher renal tubular grade (p=0.035), renal affected area (p<0.001), and SQS (p=0.001) than the Mg+colistin group. The results of the study suggested that Mg sulfate may have a nephrotoxicity-reducing effect on colistin.

The effect of taxifolin on oxidative ovarian damage and reproductive dysfunctions induced by antipsychotic drugs in female rats.

AIM: Typical antipsychotics (TAPs) are commonly used to treat schizophrenia and bipolar disorder. However, extrapyramidal disorders, hyperprolactinemia, and reproductive dysfunctions have been observed in women during the use of TAPs. For this reason, less toxic and prolactin-sparing atypical antipsychotic (AAP) drugs such as clozapine (CLN) have been developed. The aim of this study is to investigate the effect of taxifolin on possible ovarian and reproductive toxicity associated with CLN and haloperidol (HPL) in female Wistar albino rats. METHODS: The rats were grouped as healthy control group (HCG), CLN, HPL, taxifolin + clozapine (TCL), and taxifolin + haloperidol (THL). Drugs were administered to the groups for 28 days. At the end of that time, ovarian tissues of six rats from each group were taken for histopathological and biochemical analyses. Remaining six rats in groups were examined for evaluation of reproductive dysfunctions. RESULTS: Severe degeneration and vacuolization were observed in the primary, secondary, and primordial follicles of the ovarian tissues of CLN- and HPL-treated groups, of which malondialdehyde (MDA) level was high and total glutathione (tGSH) level was low. In the taxifolin-treated groups, taxifolin significantly prevented the increase of MDA level and decrease of tGSH level, and the severity of histopathological damage was found to be lower. In addition, it was found that taxifolin significantly prevented infertility and delay in pregnancy associated with CLN and HPL. CONCLUSIONS: The results of this experiment suggest that taxifolin can be beneficial in treating oxidative ovarian damage, infertility, and reproductive dysfunctions induced by CLN and HPL.

Diagnostic value of thymus and activation-regulated chemokine and of periostin in eosinophilic asthma: A prospective study.

Background: Serum thymus and activation-regulated chemokine (TARC) and periostin are reliable biomarkers in eosinophilic asthma. Objective: This study was carried out to determine the use of periostin and TARC as biomarkers in asthma and to compare the superiority of one over the other, especially in asthma with an eosinophilic phenotype. Methods: The study was conducted with 87 patients with asthma and 42 healthy control subjects. Patients with asthma were also divided into eosinophilic and non-eosinophilic phenotypes. A pulmonary function test was performed in all the participants, and serum and induced sputum TARC, periostin concentrations, eosinophils, and total immunoglobulin E values were examined. Results: TARC and periostin levels were significantly higher in the asthma group than in the control group (p < 0.001). The serum TARC level in the eosinophilic group was significantly higher than in the non-eosinophilic and control groups (p < 0.001). The induced sputum TARC level was significantly higher in the non-eosinophilic group than in the control group (p < 0.001). The TARC and periostin levels of the patients were evaluated by using receiver operator characteristic analysis. The cutoff value for TARC was determined to be 1415.39 ng/L; likewise, the cutoff value for periostin was 107.60 ng/L. The present study detected that serum levels of TARC correlated to serum levels of periostin (r = 0.54; p = 0.032). Furthermore, when evaluating correlations between serum and sputum levels, there was a correlation detected between TARC and periostin in serum, whereas this correlation was stronger in sputum: r = 0.66, p = 0.020; and r = 0.62, p = 0.028, respectively. Conclusion: Serum and sputum TARC and periostin may contribute for monitoring the improvement of patients, particularly those with asthma. Furthermore, TARC was a more reliable biomarker than periostin for patients with eosinophilic asthma.

Can magnesium sulfate prophylaxis reduce colistin nephrotoxicity?

The study aimed to investigate the role of magnesium sulfate prophylaxis in nephrotoxicity caused by colistin. Thirty Wistar Albino rats were divided into four groups: control, colistin, magnesium (Mg), and Mg+colistin. The drugs were administered to the groups for seven days. Urea-creatinine values were measured at the beginning (T0) and end (T1) of the study. Malondialdehyde (MDA) levels were measured in plasma and kidney tissue, glutathione (GSH) levels were analyzed in the erythrocyte and kidney tissues. At the end of the study, the semiquantitative score (SQS) was calculated by the histopathological examination of the kidneys. Urea values significantly decreased in Mg and Mg+colistin groups compared to the baseline (p=0.013 and p=0.001). At the time of T1, these groups had significantly lower urea values than the colistin and control groups. Creatinine value was significantly increased in the colistin group compared to baseline (p=0.005), the creatinine value in the colistin group was significantly higher than the Mg+colistin group (p=0.011). Plasma MDA levels were significantly higher in the colistin group compared to the other groups at the time of T1 (p<0.001). The Mg+colistin group had lower renal MDA levels than the colistin group. The colistin group had significantly higher renal tubular grade (p=0.035), renal affected area (p<0.001), and SQS (p=0.001) than the Mg+colistin group. The results of the study suggested that Mg sulfate may have a nephrotoxicity-reducing effect on colistin.

Diagnostic value of thymus and activation-regulated chemokine and of periostin in eosinophilic asthma: A prospective study.

BACKGROUND: Serum thymus and activation-regulated chemokine (TARC) and periostin are reliable biomarkers in eosinophilicasthma. OBJECTIVE: This study was carried out to determine the use of periostin and TARC as biomarkers in asthma and to comparethe superiority of one over the other, especially in asthma with an eosinophilic phenotype. METHODS: The study was conducted with 87 patients with asthma and 42 healthy control subjects. Patients with asthma were also divided into eosinophilic and non-eosinophilic phenotypes. A pulmonary function test was performed in all the participants,and serum and induced sputum TARC, periostin concentrations, eosinophils, and total immunoglobulin E valueswere examined. RESULTS: TARC and periostin levels were significantly higher in the asthma group than in the control group (p < 0.001). The serum TARC level in the eosinophilic group was significantly higher than in the non-eosinophilic and control groups(p < 0.001). The induced sputum TARC level was significantly higher in the non-eosinophilic group than in the control group(p < 0.001). The TARC and periostin levels of the patients were evaluated by using receiver operator characteristic analysis.The cutoff value for TARC was determined to be 1415.39 ng/L; likewise, the cutoff value for periostin was 107.60 ng/L. Thepresent study detected that serum levels of TARC correlated to serum levels of periostin (r = 0.54; p = 0.032). Furthermore,when evaluating correlations between serum and sputum levels, there was a correlation detected between TARC and periostinin serum, whereas this correlation was stronger in sputum: r = 0.66, p = 0.020; and r = 0.62, p = 0.028, respectively. CONCLUSION: Serum and sputum TARC and periostin may contribute for monitoring the improvement of patients, particularly those with asthma. Furthermore, TARC was a more reliable biomarker than periostin for patients with eosinophilic asthma.

Vitamin E and Selenium Reduce Prednisolone Side Effects in Rat Hearts.

Aim of this work was to determine the effects of dietary intake vitamin E and Se on lipid peroxidation (LPO) as Thiobarbituric acid reactive substances (TBARS) and on the antioxidative defense mechanisms in heart tissues of rats treated with high doses of prednisolone. 250 adult male Wistar rats were randomly divided into 5 groups and fed with normal diet. Additionally groups 3, 4, and 5 received a daily supplement in their drinking water of 20 mg vitamin E, 0.3 mg Se, and a combination of vitamin E and Se (20 mg/ 0.3 mg), respectively, for 30 days. For 3 d subsequently, control group was treated with placebo, and remaining four groups were injected intramuscularly with 100 mg/kg prednisolone. After last administration of prednisolone, 10 rats from each group were killed at 4, 8, 12, 24, and 48 h and the activities of antioxidant enzymes and the levels of GSH and TBARS were measured. GSH-Px, CAT activities and GSH levels decreased starting from 4th hour to 48% and 65% of control levels by 24th hour, respectively and it reincreased to control levels at 48th hour in the prednisolone group (p < 0.001, p < 0.001). In addition, prednisolone administration led 2-fold increase in heart TBARS levels at 24th hour (p < 0.001). E vitamins and Se inhibited the increase in heart TBARS and the decrease in antioxidative enzymes levels. Therefore, It is concluded that vitamin E and Se may have a preventive role in decreasing the increase of TBARS caused by prednisolone administration in our study.

Effect of ethyl acetate extract of usnea longissima on esophagogastric adenocarcinoma in rats1.

PURPOSE: To investigate the effects of the EtOAc extract of U. longissima which is uninvestigated previously on esophagogastric cancer induced in rats with N-methyl-N-nitro-N-nitrosoguanidin (MNNG). METHODS: The anticancer activity of EtOAc extract of U. longissima was examined in the esophagogastric adenocarcinoma models induced in rats with MNNG. EtOAc extract of U. longissima, 50 and 100 mg/kg oral doses were administered once daily for six months. MNNG induced differentiated and undifferentiated type adenocarcinomas in the esophageal and gastric tissues of rats. RESULTS: EtOAc extract of U. longissima obtained from U. longissima prevented gastric and esophageal cancerogenesis induced in rats with MNNG. EtOAc extract of U. longissima did not have a lethal effect at doses of 500, 1000 and 2000 mg/kg. The prominent anticarcinogenic activity of EtOAc extract of U. longissima 50 and 100 mg/kg suggests that it is not toxic and it is selective to the cancer tissue. CONCLUSION: This information may shed light on clinical implementation of EtOAc extract of U. longissima in future.

Effect of ethyl acetate extract of usnea longissima on esophagogastric adenocarcinoma in rats

Abstract Purpose: To investigate the effects of the EtOAc extract of U. longissima which is uninvestigated previously on esophagogastric cancer induced in rats with N-methyl-N-nitro-N-nitrosoguanidin (MNNG). Methods: The anticancer activity of EtOAc extract of U. longissima was examined in the esophagogastric adenocarcinoma models induced in rats with MNNG. EtOAc extract of U. longissima, 50 and 100 mg/kg oral doses were administered once daily for six months. MNNG induced differentiated and undifferentiated type adenocarcinomas in the esophageal and gastric tissues of rats. Results: EtOAc extract of U. longissima obtained from U. longissima prevented gastric and esophageal cancerogenesis induced in rats with MNNG. EtOAc extract of U. longissima did not have a lethal effect at doses of 500, 1000 and 2000 mg/kg. The prominent anticarcinogenic activity of EtOAc extract of U. longissima 50 and 100 mg/kg suggests that it is not toxic and it is selective to the cancer tissue. Conclusion: This information may shed light on clinical implementation of EtOAc extract of U. longissima in future.

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

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

The Protective Effect of Thiamine Pryophosphate Against Sugar-Induced Retinal Neovascularisation in Rats.

The aim of this study was to investigate the effect of thiamine pyrophosphate (TPP), administered via sugar water, on retinal neovascularisation in rats. Animals were assigned to three groups, namely the TPP sugar-water group (TPSWG, n = 12), the control group (CG, n = 12) and the healthy group (HG, n = 12). The TPSWG was injected intraperitoneally with TPP once a day for 6 months. CG and HG rats were given distilled water in the same way. TPSWG and CG rats were left free to access an additional 0.292 mmol /ml of sugar water for 6 months. The fasting blood glucose (FBG) levels of the animals were measured monthly. After 6 months, biochemical, gene expression and histopathologic analyses were carried out in the retinal tissues removed from the animals after they were killed. The measured FBG levels were 6.96 ± 0.09 mmol/ml (p < 0.0001 vs. HG), 6.95 ± 0.06 mmol/ml (p < 0.0001 vs. HG) and 3.94 ± 0.10 mmol/ml in the CG, TPSWG and HG groups, respectively. The malondialdehyde (MDA) levels were found to be 2.82 ± 0.23 (p < 0.0001 vs. HG), 1.40 ± 0.32 (p < 0.0001 vs. HG) and 1.66 ± 0.17 in the CG, TPSWG and HG, respectively. Interleukin 1 beta (IL-1ß) gene expression was increased (3.78 ± 0.29, p < 0.0001) and total glutathione (tGSH) was decreased (1.32 ± 0.25, p < 0.0001) in the retinal tissue of CG compared with TPSWG (1.92 ± 0.29 and 3.18 ± 0.46, respectively). Increased vascularisation and oedema were observed in the retinal tissue of CG, while the retinal tissues of TPSWG and HG rats had a normal histopathological appearance. A carbohydrate-rich diet may lead to pathological changes in the retina even in nondiabetics, but this may be overcome by TPP administration.

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

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

Gene expression and histopathological evaluation of thiamine pyrophosphate on optic neuropathy induced with ethambutol in rats.

AIM: To compare the effects of thiamine pyrophosphate (TPP) and thiamine (TM) in oxidative optic neuropathy in rats induced by ethambutol. METHODS: The animals were divided into four groups: a control group (CG), an ethambutol control (ETC) group, TM plus ethambutol group (TMG), and TPP plus ethambutol group (TPPG). One hour after intraperitoneal administration of TM 20 mg/kg to the TMG group and TPP 20 mg/kg to TPPG group, 30 mg/kg ethambutol was given via gavage to all the groups but the CG. This procedure was repeated once daily for 90d. After that period, all rats were exposed to high levels of anaesthesia in order to investigate the gene expression of malondialdehyde and glutathione in removed optic nerve tissue and histopathologically to examine these tissues. RESULTS: Malondialdehyde gene expression significantly increased, whereas glutathione gene expression significantly decreased in the ETC group compared to the CG. TM could not prevent the increase of malondialdehyde gene expression and the decrease of glutathione, while TPP significantly could suppress. Histopathologically, significant vacuolization in the optic nerve, single-cell necrosis in the glial cells, and a decrease in oligodendrocytes were observed in the ETC group. Vacuolization in the optic nerve, a decrease in oligodendrocytes and single-cell necrosis were found in the TMG group, while no pathological finding was observed in the TPPG group except for mild vacuolization. CONCLUSION: TPP protects the optic nerve against the ethambutol-induced toxicity but TM does not. TPP can be beneficial in prophilaxis of optic neuropathy in ethambutol therapy.

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.

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

AIM: To investigate the effect of Kineret® on ischemia reperfusion (IR) injury in rat ovaries. METHODS: Rats were divided into four groups: ovarian IR (IRG); 50 mg/kg Kineret® + ovarian IR (KIR-50); 100 mg/kg Kineret® + ovarian IR (KIR-100); and sham operation (SOC). KIR-50 (n = 10) and KIR-100 (n = 10) groups received an intraperitoneal injection of Kineret® at doses of 50 and 100 mg/kg, respectively. IRG and SOC (n = 10) rat groups were given distilled water as solvent using the same method. The results were compared between the groups. RESULTS: In rats in which IR occurred, oxidant parameters, such as malondialdehyde (MDA) and myeloperoxidase (MPO), were increased, the level of proinflammatory interleukin 1 beta (IL-1ß) was elevated and total glutathione (tGSH) as an antioxidant was decreased in the ovarian tissues. Administration of Kineret® at a dose of 100 mg/kg inhibited the increase of MDA, MOP and IL-1ß and a decrease in tGSH caused by IR more significantly than administration of Kineret® at a dose of 50 mg/kg. In addition, 100 mg/kg Kineret® significantly decreased severe hemorrhage, degeneration and inflammatory signs in the follicular cells, caused by IR. Kineret® at 100 mg/kg markedly ameliorated increased apoptosis in ovarian tissue with IR more significantly than 50 mg/kg kineret. CONCLUSION: Our findings indicate that Kineret® might be useful in clinical practice for the treatment of damage that may occur as a result of ovarian torsion.

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.

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.