Investigation of the Relationship of Nesfatin-1, Adropin Levels and Claudin-2, Renalase Immunoreactivity with Kidney Function in an Experimental Hypertension Model.

OBJECTIVE: Hypertension is one of the cardiovascular diseases that causes the most mortality, and 95% of the causes are unknown. The aim of the study was to examine the possible correlation of nesfatin-1 levels, adropin levels, claudin-2 immunoreactivity (claudin-2 expression in the renal proximal tubule), and renalase immunoreactivity (renalase expression in the renal proximal tubule) with arterial blood pressure, kidney function, and kidney damage. METHODS: Adult male Sprague Dawley rats were divided into control and hypertension groups (8 per group). Angiotensin II vehicle was given to the control group and angiotensin II (0.7 mg/kg/day) to the hypertension group, both via an osmotic mini pump for 7 days. The animals blood pressures were measured by tail cuff plethysmography on days 1, 3, 5, and 7. On day 7, 24-hour urine, blood, and tissues were collected from the rats. RESULTS: In the hypertension group compared with the control group, there was an increase in systolic blood pressure levels after day 1. While claudin-2 immunoreactivity was reduced in the kidneys, renalase immunoreactivity was increased. There was a decrease in creatinine clearance and an increase in fractional potassium excretion (P < .05). CONCLUSION: Our results showed that claudin-2 and renalase are associated with renal glomerular and tubular dysfunction and may play discrete roles in the pathogenesis of hypertension. We believe that these potential roles warrant further investigation.

Development of pancreatic islet cells in the extrahepatic bile ducts of rats with experimentally-induced metabolic syndrome.

CONTEXT: There is data about the existence of some endocrine cells in the epithelial layer of the bile duct in humans and rats. OBJECTIVE: We evaluated Ghrelin-, Insulin-, Glucagon- and Somatostatin-positive cells in peribiliary glands, mast cells, and nerve fibres. MATERIALS AND METHODS: Wistar rats were used for dietary manipulation with a 15% fructose solution for 12 weeks. Tissue samples were elaborated with immunohistochemistry for Insulin, Glucagon, Ghrelin, and Somatostatin. Glucose and lipid parameters were studied. RESULTS: In treated animals, Ghrelin+ and Insulin+ cells in perybiliary glands (PBGs) were significantly increased. In the male fructose group there was a significant increase of the homeostasis model assessment insulin resistance (HOMA-IR). CONCLUSIONS: Stem/progenitor cells in extrahepatic bile tree (EHBT) could be a source of Insulin-producing cells in metabolic syndrome. Fructose treatment induces the increase of Ghrelin+ and Insulin+ cells in PBGs and the elevation of Insulin and Ghrelin plasma concentration.

The comparison of endothelial function of moderate intensity interval exercise with continuous exercise in healthy men.

Background/aim: Exercise enhances endothelium-dependent vasodilation; however, it is unclear whether intermittent exercise has a different effect on vascular endothelial function compared to continuous exercise. This study aimed to compare vascular endothelial function following intermittent exercise including short rest intervals with continuous exercise, both at the anaerobic threshold level. Materials and methods: Peak oxygen consumption (VO2 peak) and anaerobic threshold were measured in physically active healthy young men (n = 12) by breath-by-breath analysis. After completion of intermittent exercise consisting of eight 1-min long intervals at the anaerobic threshold intensity with 75-s rest periods, total work was calculated. Equivalent work was done during continuous exercise. Immediately after the two exercise periods, venous blood lactate, endothelial nitric oxide synthase (eNOS), endothelin-1, N-terminal proANP (NTproANP), N-terminal proBNP (NTproBNP), and N-terminal proCNP (NTproCNP) levels were measured. Brachial artery flow-mediated dilatation (FMD) was measured before exercise and 30 min after exercise. Results: Mean VO2 peak level was 33.42 ± 5.9 ml/min/kg and anaerobic threshold level was 47.33 ± 5.85%. Lactate levels following continuous exercise were higher than levels following intermittent exercise (27.76 ± 7.43 mg/dl, 18.54 ± 4.87 mg/dl respectively; p˂0.05). Endothelin-1, eNOS, NTproANP, NTproBNP, and NTproCNP levels were similar after both modalities of exercise (p > 0.05). No significant difference was found in FMD response when comparing intermittent and continuous exercise (7.05 ± 15.11%, 2.49 ± 16.24% respectively; p > 0.05). Conclusion: Since blood lactate levels are higher following continuous exercise, individuals who find difficulty exercising may prefer an intermittent form of exercise. However, both intermittent and continuous exercise at the anaerobic threshold level seem to not produce a significant acute change in endothelial function in healthy men.

Investigation of Kisspeptin Role in Experimental Kidney Ischemia/Reperfusion Injury.

INTRODUCTION: Kisspeptin is biologically active peptide encoded by the KISS1 gene that is structurally found in the kidney tubule, collecting duct and vein smooth muscle cells. AIM: We aimed to investigate the role of kisspeptin in kidney function and renal pathophysiology in experimental kidney ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: Male Spraque-Dawley rats were divided into control and I/R groups (n=8). Both kidney vessels of I/R group rats were clamped and subjected to ischemia for 60 minutes and reperfusion for 48 hours. After the reperfusion period blood samples and kidney tissue were collected under anesthesia. RESULTS: Levels of urea, creatinine (. CONCLUSIONS: The present study has shown that the levels of kisspeptin change in kidney damage and thus the kisspeptin may play a role in the regulation of renal function and in the pathophysiology of acute kidney injury.

The Effects of Irisin on Nω-Nitro-L-arginine Methyl Ester Hydrochloride-Induced Hypertension in Rats

Background: The cause of about 95% of hypertension, an important public health problem, is unknown. Intensive studies are underway to understand the physiopathology of hypertension. Irisin, a newly discovered hormone, has been reported to dilate vascular smooth muscle and lower blood pressure acutely. Aims: To investigate the effects of chronic irisin treatment on blood pressure and renal functions in a hypertension model established by nitric oxide synthase inhibition by treatment with Nω-nitro-L-arginine methyl ester hydrochloride. Study Design: Animal experimentation. Methods: Male Sprague−Dawley rats were divided into four groups (n=8). Control and irisin groups received an intravenous saline injection, hypertension and hypertension + irisin (hypertension + irisin) groups received 1.5 mg/100 g Nω-nitro-L-arginine methyl ester hydrochloride. Nω-nitro-L-arginine methyl ester hydrochloride (150 mg/L) was added to the drinking water of rats in groups hypertension and hypertension + irisin for three weeks. In the second week of the experiment, irisin (50 nmol/day) was given to rats in groups irisin and hypertension + irisin, and saline was administered to rats in groups control and hypertension for two weeks through subcutaneously placed osmotic minipumps. Blood pressure was measured by the tail-cuff plethysmography method. On the twenty-first day of the experiment, 24-hour urine, blood, and both kidneys of the rats were collected. Results: The hypertension group had elevated systolic, diastolic, and mean arterial blood pressure values compared with the control group, with decreased glutathione levels in tissue and serum, but an increase in serum oxidized glutathione level (p<0.05). Histopathologically, increased tubular injury, cast formation, glomerular sclerosis, and peritubular fibrosis levels were observed (p<0.05). Irisin treatment did not cause any significant change in blood pressure, renal functions, and injury scores. However, renal nitric oxide levels significantly increased, and endothelial nitric oxide synthase immunoreactivity was determined to be reduced (p<0.05). Conclusion: Treatment with chronic irisin at a physiological dose does not reduce blood pressure in an experimental model of hypertension. In different models of experimental hypertension, the effects of irisin administration at different doses and at different periods should be thoroughly investigated.

Indomethacin-induced gastric damage in rats and the protective effect of donkey milk.

INTRODUCTION: Indomethacin is an anti-inflammatory drug with clearly known side effects on gastric mucosa. New treatment and side effect prevention methods are being studied. Donkey milk, as a nutritional support, has recently come into the spotlight with its anti-oxidant features, high antibody content and low allergenic properties. In this study, we investigated donkey milk's possible protective effect against acute gastric mucosal damage by indomethacin. MATERIAL AND METHODS: Four groups, each composed of 8 rats, were created. Rats in the first and third groups were fed with standard rat chow, while those in the second and fourth groups were additionally fed with 25 mg/kg of donkey milk per day via nasogastric gavage. On the 11th day gastric mucosal damage was induced by oral administration of 30 mg/kg of indomethacin to the rats in groups 3 and 4. Six h later all rats were sacrificed and their stomachs were removed for macroscopic and microscopic evaluation as well as biochemical examination of glutathione (GSH) and malondialdehyde (MDA) levels. Tumor necrosis factor-α (TNF-α) expression in the gastric mucosa was evaluated immunohistochemically. RESULTS: In the donkey milk-indomethacin group, total area of erosion and degree of linear ulceration were significantly lower than in the standard food-indomethacin group (p < 0.05). Also, GSH levels were increased and MDA levels were decreased significantly in this group. Tumor necrosis factor-α expression was more prevalent and stronger in the gastritis group, while lower expression was observed in the donkey milk group. CONCLUSIONS: Donkey milk was observed to have significant protective effects against gastric damage induced by indomethacin.

The Effects of Baicalin on Myoglobinuric Acute Renal Failure in Rats.

BACKGROUND: Myoglobinuric acute kidney injury is a uremic syndrome that develops due to damage of skeletal muscle. Free radicals and nitric oxide play an important role in the pathogenesis of myoglobinuric acute kidney injury. Baicalin has multiple bioactivities, including antimicrobial, anti-inflammatory and antioxidant properties and is a potent free radical scavenger. AIMS: To investigate the nephroprotective mechanism of baicalin on myoglobinuric acute kidney injury. STUDY DESIGN: Animal experimentation. METHODS: In our study, male Sprague Dawley rats were divided into 4 groups. Control (n=8), Baicalin (n=8), myoglobinuric acute kidney injury (n=10) and myoglobinuric acute kidney injury + baicalin (n=10). The rats were deprived of water for 24 hours before receiving intramuscular injection. The control and baicalin groups were injected intramuscularly with saline (8 ml/kg), and the myoglobinuric acute kidney injury and myoglobinuric acute kidney injury + baicalin groups were given 50% glycerol 8 ml/kg. One hour later, the control and myoglobinuric acute kidney injury groups received saline intraperitoneally, and the baicalin and myoglobinuric acute kidney injury + baicalin groups were given 200 mg/kg baicalin. Twenty-four hours after the glycerol injection, urine and blood samples were taken, and the kidneys of the rats were harvested under intraperitoneally injections of anaesthesia. RESULTS: We found that the levels of creatinine, urea, nitric oxide, alanine transaminase, aspartate aminotransferase, creatine kinase in serum samples, malondialdehyde, nitric oxide, inducible nitric oxide synthase, and endothelial nitric oxide synthase concentrations in renal tissue were increased in the myoglobinuric acute kidney injury group compared with the control group (p<0.05). The nitric oxide and glutathione levels in the kidney were significantly decreased in the myoglobinuric acute kidney injury + baicalin group compared with the myoglobinuric acute kidney injury group (p<0.05). There were no significant differences between any other parameters. CONCLUSION: Our results did not show any protective effect of baicalin on myoglobinuric acute kidney injury, possibly because the different effective factors in the pathogenesis of experimental myoglobinuric acute kidney injury used in this experiment deviate from other experimental models. Moreover, detailed studies are needed to clarify the effects of baicalin in different doses and treatment durations in glycerol-induced acute kidney injury model.

The effect of high protein diet and exercise on irisin, eNOS, and iNOS expressions in kidney.

Long-term effects of high protein diets (HPDs) on kidneys are still not sufficiently studied. Irisin which increases oxygen consumption and thermogenesis in white fat cells was shown in skeletal muscles and many tissues. Nitric oxide synthases (NOS) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. We aimed to investigate the effects of HPD, irisin and NO expression in kidney and relation of them with exercise and among themselves. Animals were grouped as control, exercise, HPD and exercise combined with HPD (exercise-HPD). Rats were kept on a HPD for 5 weeks and an exercise program was given them as 5 exercise and 2 rest days per week exercising on a treadmill with increasing speed and angle. In our study, while HPD group had similar total antioxidant capacity (TAC) levels with control group, exercise and exercise-HPD groups had lower levels (p < 0.05). Kidneys of exercising rats had no change in irisin or eNOS expression but their iNOS expression had increased (p < 0.001). HPD-E group has not been observed to cause kidney damage and not have a significant effect on rat kidney irisin, eNOS, or iNOS expression. Localization of irisin, eNOS, and iNOS staining in kidney is highly selective and quite clear in this study. Effects of exercise and HPD on kidney should be evaluated with different exercise protocols and contents of the diet. Irisin, eNOS, and iNOS staining localizations should be supported with various research studies.

Asymmetric dimethylarginine in experimental breast cancer; action of Vitamin C and E.

OBJECTIVE: To investigate the arginase-nitric oxide synthase paradox through asymmetric dimethylarginine, symmetric dimethylarginine and nitric oxide levels, and to see the effect of antioxidant vitamins on this mechanism of cancer action. METHODS: The animal-based study was conducted at Trakya University, Turkey, in 2008, and comprised mice that were divided into five equal groups. Group 1 had healthy controls, while in the other four groups breast cancer was induced. Group 2 received saline solution, group 3 received 200 mg/kg/day vitamin C (tumour +vit C), group 4 received 300 mg/kg/day vitamin E (tumour +vitE) and group 5 received both 200 mg/kg/day vitamin C and 300 mg/kg/day vitamin E (tumour +vit C+vit E) for 15 days intra-peritoneally.Arginine, asymmetric dimethylarginine, symmetric dimethylarginine and nitric oxide levels were determined in each group. RESULTS: The 50 mice in the study were divided into five groups of 10(20%) each. Plasma arginine levels were significantly decreased, asymmetric dimethylarginine and symmetric dimethylarginine levels were increased, while plasma nitric oxide level was significantly decreased in group 2. There was no statistically significant difference in treatment groups for all parameters (p>0.05 each). CONCLUSIONS: Understanding of the mechanism may help to develop new anti-cancer agents.

Protective effect of sildenafil on liver injury induced by intestinal ischemia/reperfusion.

BACKGROUND: This study evaluated the protective effect of sildenafil on liver injury induced by intestinal ischemia-reperfusion. METHODS: Forty female Sprague Dawley rats were divided into 4 groups: sham-control (SC), ischemia (I), ischemia-reperfusion (IR), and ischemia-reperfusion+sildenafil (SIL; sildenafil gavaged at 50mg/kg before operating). A 2-h ischemia-reperfusion was performed by clamping the superior mesenteric artery. Liver function, plasma alanine (ALT) and aspartate (AST) aminotransferase, and intestinal and liver malondialdehyde (MDA) were measured at the end of the experiment. Intestinal and liver tissue damage was examined by histology. Liver samples were immunologically stained for endothelial nitric oxide synthase (eNOS) and proliferating cell nuclear antigen (PCNA). RESULTS: The ALT and AST levels were highest in the IR group and were lower in the SIL group (p<0.05). Intestinal MDA levels were statistically higher in the IR group than in the SC, I and SIL groups. Liver MDA levels were significantly higher in the IR group than in the I and SC groups (p<0.05) and higher than in the SIL group (p>0.05). Intestinal damage based on Chiu scoring was more severe in the IR than in the SIL group (p<0.05). Sildenafil reduced damage and also increased eNOS and PCNA immunoreactivity in liver tissue. CONCLUSIONS: Sildenafil shows a protective effect on intestinal ischemia-reperfusion-induced liver injury, possibly by decreasing vascular resistance through increased nitric oxide levels.

The alteration of asymmetric dimetilarginine (ADMA) levels in cardiac and gastrocnemius muscles following radioactive iodine application in guinea pigs and the effect of L-carnitine on this alteration.

PURPOSE: Tissue levels of asymmetric dimetilarginine (ADMA) and symmetric dimetilarginine (SDMA) were investigated in cardiac ventricle and gastrocnemius muscles of guinea pigs treated with radioactive iodine (RAI) alone or in combination with L-carnitine (LC). MATERIAL AND METHODS: Group 1 received no treatment (control group). Group 2 received a total dose of 30 mCi⁻¹kg⁻¹ body weight iodine-131 alone. Group 3 received 200 mg⁻¹kg⁻¹ of LC for 10 days alone. Group 4 received 200 mg⁻¹kg⁻¹ of LC plus RAI therapy. Free thyroid hormones, ADMA and SDMA concentrations were measured. RESULTS: Serum free thyroid hormone concentrations were found decreased in the RAI and LC-RAI groups after RAI application. A significant decrease in ADMA and SDMA concentration was observed in ventricle muscle following RAI application. The LC-RAI group had significantly decreased ADMA levels in ventricle muscle compared with those of the control group. Similarly, SDMA concentrations in ventricle and gastrocnemius muscles of the LC-RAI groups were significantly lower than those of the control groups. CONCLUSIONS: Our results indicated that RAI appears to exert an inhibitory effect on ADMA and SDMA levels of ventricular muscle. LC administration when given adjuvant to RAI therapy may cause a marked decrease in ADMA concentrations of both ventricular and gastrocnemius muscles.

Protective effect of flaxseed oil on renal injury in hyperlipidaemic rats: the effect of flaxseed oil on hyperlipidaemia.

This study evaluated the possible effects of flaxseed oil on renal damage associated with hyperlipidaemic rats. Wistar albino male rats were divided into three groups. Group I was fed with a pellet chow. Group II was fed with a high cholesterol diet (HCD) consisting of 5% cholesterol and 0.35% cholic acid added to the pellet chow. Group III was fed with the same HCD, but were orally treated with a dose of 15 mg/kg body wt/day flaxseed oil. Flaxseed oil treatment started 1 week before and continued throughout the 22 weeks of the HCD. At the end of the experiment, renal tissue and blood samples were collected. The biochemical and histopathological findings confirmed renal damage in hypercholesterolaemia conditions. Flaxseed oil reduced the hypercholesterolaemia-induced increase in the serum levels of total cholesterol, LDL and urea. Oil red O stain revealed that lowered serum lipid was accompanied by a decreased deposition of neutral lipid. Flaxseed oil effectively reversed these abnormalities, verifying the protective effects of flaxseed oil in ameliorating renal injuries associated with hypercholesterolaemia.

Capecitabine-related intracranial hypotension syndrome mimicking dural metastasis in a breast cancer patient: case report and review of the literature.

Spontaneous intracranial hypotension (SICH) is an entity, which is secondary to iatrogenic manipulation and breaching of dura. Postural headache in patients should be suspected, cranial magnetic resonance imaging (MRI) is essential for precise diagnosis. Hallmark of MRI is regular shape of pachymeningeal gadolinium enhancement and subdural effusion. It may mimic central nervous system (CNS) metastasis. Prevention of such cases from receiving cranial radiotherapy by misinterpretation of the gadolinium enhancement as CNS metastasis is an important issue. Capecitabine is an antineoplastic agent, of which metabolites can cross blood-brain barrier in CNS via epithelial tissue. It may cause decrease in CSF production. SICH might be the clinical reflection of this decrease in CSF production. Review of the English literature revealed limited data because of the very little experience with oncologic patients suffering from intracranial hypotension. We report a case of spontaneous intracranial hypotension during capecitabine treatment. Patient was completely well following drug discontinuation and supportive treatment.

Tissue damage in rat ovaries subjected to torsion and detorsion: effects of L-carnitine and N-acetyl cysteine.

We aimed to evaluate histopathological changes, to detect HIF-1alpha staining intensities and to determine MDA levels in rat ovaries, which were subjected to torsion and detorsion and treated with L -carnitine or N-acetyl cysteine (NAC). Forty-eight prepubertal female Sprague-Dawley rats were divided into five groups (n = 8): 1, control; 2, ischemia; 3, reperfusion; 4, L -carnitine; and 5, NAC groups. In groups 3, 4 and 5, an ischemic period of 3 h was followed by reperfusion for 24 h. In groups 4 and 5, ischemia was performed and either L -carnitine or NAC was infused intraperitoneally 30 min before reperfusion. Ovarian tissues were examined histopathologically; tissue MDA levels and serum IL-6 levels were determined biochemically. HIF-1alpha was applied to all ovaries immunohistochemically. Total tissue damage scores, tissue MDA levels and HIF-1alpha scores, were significantly higher in group 2 (all P < 0.001) than group 4, and group 3 than group 4 (P < 0.001, P = 0.05 and P < 0.001, respectively). They were also significantly higher in group 2 (all P < 0.001) than group 5. When group 3 is compared to group 5, total tissue damage scores and tissue MDA levels were significantly higher in the former (P < 0.01 and P < 0.001, respectively). Serum IL-6 levels were significantly higher in group 2 when compared to groups 1, 4 and 5 (all P < 0.01). The degree of tissue damage of the torsioned ovaries decreased after a reperfusion period of 24 h in the torsioned ovaries. However, ovaries of both L -carnitine and NAC groups showed better recovery than the reperfusion group.

Effect of curcumin on ipsilateral and contralateral testes after unilateral testicular torsion in a rat model.

OBJECTIVE: The aim of the study was to determine the protective effect of curcumin on testicular ischemia-reperfusion (I/R) injury. MATERIALS AND METHODS: 32 male rats were divided into four groups (n = 8): group 1: control; group 2: ischemia; group 3: I/R, and group 4: I/R+CUR. Curcumin (150 mg/kg, p.o.) was administered before 30 min of reperfusion in group 4. Malondialdehyde (MDA) levels, Johnsen's testicular biopsy scores, and mean seminiferous tubule diameter measurements were evaluated in testes. In addition, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expressions were evaluated immunohistochemically. RESULTS: MDA levels in control groups were significantly lower than other groups in ipsilateral and contralateral testes. Johnsen's scores in the control group were significantly higher than in other groups. MDA levels and Johnsen's scores in the I/R+CUR group were similar to the ischemia and I/R groups in ipsilateral and contralateral testes. The immunoreactivity of iNOS and eNOS were increased in I/R ipsilateral testicular groups. After I/R, iNOS and eNOS expression increased slightly in contralateral groups. Additionally, the curcumin treatment decreased iNOS and eNOS immunoreactivity in ipsilateral and contralateral testes. CONCLUSION: The results suggest that curcumin did not protect the unilateral nor contralateral testes. This observation may depend on inhibition of iNOS and eNOS due to inhibition of the antioxidant, anti-inflammatory effects of nitric oxide.

Influence of N-acetylcysteine on renal toxicity of cadmium in rats.

The aim of this study was to investigate the ability of N-acetylcysteine (NAC) to prevent cadmium (Cd)-induced renal damage and whether NAC would reverse cadmium damage to the kidney. Fifty adult male rats were divided into five experimental groups: group 1 received tap water for 3 months and 7 days, group 2 received cadmium chloride (CdCl(2)) for 3 months, group 3 (NAC cotreatment group) received CdCl(2) and 0.5% NAC in tap water for 3 months, group 4 received CdCl(2) in tap water for 3 months and 3 months later received only tap water for 7 days, and group 5 (NAC posttreatment group) received CdCl(2) in tap water for 3 months and 3 months later received 2% NAC in tap water for 7 days. NAC significantly decreased the elevated kidney malondialdehyde levels, as a marker of lipid peroxidation, in both cotreatment and posttreatment modalities. Cotreatment and posttreatment with NAC significantly increased kidney superoxide dismutase enzyme activity and glutathione level but did not change kidney catalase enzyme activity. NAC decreased fractional excretion of sodium in posttreatment group. Neither Cd nor NAC affected the glomerular filtration rate (GFR). Cotreatment and posttreatment with NAC reduced the effects of Cd on proximal tubules. It was found that NAC showed these effects without changing kidney accumulation of cadmium. Exogenously administrated NAC might reduce toxic effects of Cd on the kidney without any reduction in tissue Cd level.

Methylene blue increases contralateral testicular ischaemia-reperfusion injury after unilateral testicular torsion.

1. Testicular ischaemia-reperfusion injury is commonly seen in childhood. Infertility occurs in 25% of patients after unilateral testicular ischaemia. It is has been reported that methylene blue has a positive effect in the reparation of ischaemia-reperfusion injury in different tissues. Therefore, we hypothesized that methylene blue may prevent the hazardous effects of ischaemia-reperfusion injury in testicular tissue after unilateral testicular torsion. 2. Thirty-two prepubertal Wistar-albino rats were divided into four groups. Testicular torsion was created by rotating the right testis 720 degrees in a clockwise direction for 5 h in all groups except for Group C, which was the sham control group. In Group T, bilateral orchiectomy was performed following the torsion period. In Group TD, both testes were removed 5 days after the torsion period. In Group MB, methylene blue (1 mg/kg, i.p.) was administered 40 min before detorsion and once daily over 5 days; then, both testes were harvested. Tissue levels of malondialdehyde (MDA), serum levels of creatine kinase (CK), mean testicular biopsy score (MTBS) and mean seminifer tubule diameter (MSTD) were determined. 3. There was a significant difference in MTBS between Groups T and TD (P < 0.05) in both ipsilateral and contralateral testes. In the contralateral testis, treatment with methylene blue decreased MTBS and MSTD (P < 0.05) and increased MDA levels (P < 0.05). In Group T, mean serum CK concentrations were higher than in any of the other groups (P < 0.05). 4. After 5 h of unilateral testicular torsion and a 5 day reperfusion period, serious tissue damage occurred on both the ipsilateral and contralateral sides. Serum CK concentrations may be an indicator for ischaemia, but not for ischaemia-reperfusion injury. Contrary to our hypothesis, methylene blue increased contralateral testicular damage after unilateral testicular torsion and exacerbated oxidative events.

Protective effects of L-carnitine and alpha-lipoic acid in rats with adjuvant arthritis.

Free radicals play an important role in the pathophysiology of adjuvant arthritis. The purpose of this study was to assess the efficacy of L-carnitine (LC) and alpha-lipoic acid (alpha-LA) which are known to have antioxidant effects, in the treatment of adjuvant arthritis. Arthritis model was created by the administration of complete Freund's adjuvant (CFA) in 32 of 40 male Sprague-Dawley rats. The rats were divided into five groups. Rats in Group I served as controls and received 0.1 ml kg(-1) saline. Group II received only 0.1 ml of CFA and served as the CFA-control for the other groups. Groups III-V, after being injected with CFA, were treated with LC, alpha-LA or diclofenac, respectively. Levels of malondialdehyde (MDA) and glutathione (GSH) were measured in plasma samples. Enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. The paws of rats were evaluated histopathologically to investigate the anti-inflammatory effects. TNF-alpha levels were measured for the evaluation of inflammation. In Group II plasma MDA increased, levels of glutathione decreased, enzyme activities of SOD and GPx decreased. Histopathological damage increased in the paws of the rats in this group. MDA levels decreased in Groups III-V when compared with Group II. GSH levels significantly increased in Group III and IV than Group V. SOD activity of Group IV was higher than Group III and V. TNF-alpha levels were significantly lower in Group IV and V. LC and alpha-LA seemed to have protective effects against oxidative damage in adjuvant arthritis model.

Protective role of carnitine in breast cancer via decreasing arginase activity and increasing nitric oxide.

Breast cancer remains one of the most common types of cancer. High levels of arginase and ornithine in different carcinomas may indicate their relation to cancer. Carnitine is a cofactor required for the transformation of free long-chain fatty acids into acetyl-carnitines. We have examined the protective effect of carnitine and the possibility that it disturbs arginase-nitric oxide (NO) interaction. Histopathological examination, arginase activity, ornithine and NO levels were determined in tumour tissues. Mitotic cells significantly decreased in the treatment group. Tissue arginase activity and ornithine levels decreased significantly with carnitine. NO levels were significantly higher in the treatment group. One of the possible mechanisms of carnitine's protective role in tumour progression might be its promotion of NO. This mechanism could decrease the production of tumour-promoting agents, polyamines, and increase the production of NO, thereby exerting a protective effect on cancer development.

The protective effects of melatonin and vitamin E against renal ischemia-reperfusion injury in rats.

Reactive oxygen species (ROS) were shown to contribute to the cellular damage induced by ischemia-reperfusion. The purpose of this study was to investigate and compare the efficiency of melatonin and vitamin E in the reduction of injury induced by ROS in a rat model of renal ischemia-reperfusion. Twenty-four Wistar-albino rats were divided into four groups. Rats in the Sham group were given saline 1 mL/kg, intraperitoneally (ip) 72 h, 48 h, 24 h, and 30 min before the sham operation. Rats in ischemia-reperfusion (IR), IR+Melatonin, and IR+Vitamin E groups were given saline (1 mL/kg), melatonin (10 mg/kg), and vitamin E (100 mg/kg) ip, respectively, 72 h, 48 h, 24 h, and 30 min before the ischemia for 60 min, followed by reperfusion for 60 min. The blood samples and kidney tissues of the rats were taken under anesthesia. Ischemia-reperfusion significantly increased urea, creatinine, and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) and catalase (CAT) activities. Histopathological findings of the IR group confirmed that there was renal impairment by cast formation and tubular necrosis in the tubular epithelium. In the IR+Melatonin group, while MDA levels significantly decreased, SOD activities increased. In the IR+Melatonin group, the level of tubular necrosis and cast formation are significantly decreased than those seen in the ischemia-reperfusion group. Melatonin in particular was effective to reverse hot ischemia of kidney by its antioxidant effects. These results may indicate that melatonin pretreatment protects against functional, biochemical, and morphological damage better than vitamin E in renal ischemia-reperfusion injury.