Nurettin Aydogdu

PROTECTIVE EFFECTS OF l-CARNITINE ON MYOGLOBINURIC ACUTE RENAL FAILURE IN RATS

1 Muscle injury (rhabdomyolysis) is one of the causes of acute renal failure (ARF). Iron, free radicals and nitric oxide (NO) play a critical role in the pathogenesis of glycerol‐induced myoglobinuric ARF. l‐Carnitine is an anti‐oxidant and prevents the accumulation of end‐products of lipid peroxidation. Therefore, the aim of the present study was to investigate the effects of l‐carnitine on myoglobinuric ARF induced by intramuscular (i.m.) hypertonic glycerol injection. 2 Sprague‐Dawley rats were divided into three groups. Rats in group 1 (n = 8) were given saline, whereas those in groups 2 (n = 10) and 3 (n = 10) were injected with glycerol (10 mL/kg, i.m.). Concomitant with and 24 h after glycerol injection, l‐carnitine (200 mg/kg, i.p.) was administered to group 3 rats. Forty‐eight hours after glycerol injection, blood samples and kidney tissues were taken from anaesthetised rats. 3 Plasma creatine kinase (CK) activity, urea, creatinine and NO levels, as well as kidney tissue superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzyme activity and malondialdehyde (MDA) and glutathione (GSH) levels, were determined. In the kidney tissue, histopathological changes and iron accumulation in the tubular epithelium were also investigated. 4 Glycerol treatment caused severe ARF: a marked renal oxidative stress, significantly increased CK activity, urea and creatinine levels and decreased plasma NO levels. Histopathological findings in group 2 rats confirmed that there was renal impairment by cast formation and tubular necrosis and a marked increase in iron accumulation in the tubular epithelium. All these factors were significantly improved by l‐carnitine supplementation. 5 These results may indicate that l‐carnitine treatment protects against functional, biochemical and morphological damage and iron accumulation in glycerol‐induced myoglobinuric ARF in rats. In this model, the protective effect of l‐carnitine treatment may provide a new insight into the treatment of rhabdomyolysis‐related ARF.

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.

Effects of caffeic acid phenethyl ester on glycerol-induced acute renal failure in rats

1. Free radicals and nitric oxide (NO) play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). The aim of the present study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an anti‐oxidant, on the myoglobinuric ARF induced by intramusculer hypertonic glycerol injection.

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 carnitines 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.

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.

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. Copyright

ROSIGLITAZONE, AN AGONIST OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA, PREVENTS CONTRALATERAL TESTICULAR ISCHAEMIA–REPERFUSION INJURY IN PREPUBERTAL RATS

1 Rosiglitazone plays a positive role in the reparation of ischaemia–reperfusion (I/R) injury in different tissues. Thus, we examined its biochemical and histological effects on the contralateral testes to determine whether exogenous rosiglitazone affords any protection against testicular damage. 2 Forty‐eight prepubertal male Wistar‐Albino rats were divided into six groups. Testicular torsion was created by rotating the right testis 720° in a clockwise direction for 5 h in all groups except group I, which was the sham‐control group. In group II, bilateral orchiectomy was performed following the torsion period. After detorsion both testes were removed in the fifth hour in group III and on the seventh day in group IV. In group V, one‐shot rosiglitazone (4 mg/kg) was administered 40 min before detorsion and both testes were removed following the torsion period. In group VI, rosiglitazone was administered (4 mg/kg) 40 min before detorsion and for 7 days, and then both testes were harvested. The tissue levels of malondialdehyde (MDA) were measured and mean testicular biopsy score (MTBS) and mean seminiferous tubule diameter (MSTD) were examined. Immunoexpression of endothelial nitric oxide synthase (eNOS) in testes tissues was investigated by immunohistochemical studies. 3 In the contralateral testis, the MTBS and MSTD values of group VI were significantly higher than those in group IV. Immunohistochemically, mild eNOS immunostaining was present in the germ cells of the contralateral testes in group IV after I/R. In group VI, intense eNOS immunoreactivity was seen in the contralateral testes. 4 Rosiglitazone reduces contralateral testicular damage formed after unilateral testicular torsion and alleviates the oxidative events.

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.

Melatonin reduces nitric oxide via increasing arginase in rhabdomyolysis-induced acute renal failure in rats.

Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger. In addition to a direct scavenging effect on nitric oxide (NO), its inhibitory effect on nitric oxide synthase (NOS) activity has been also reported. L-arginine is the substrate for both NOS and arginase. It has been suggested that there is a competition between arginase and NOS and that they control each others level. NO plays a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). In this study, the authors aimed to investigate the effect of melatonin on arginase activity, ornithine, and NO levels on the myoglobinuric ARF formed by intramuscular (im) injection of hypertonic glycerol. Forty rats were randomly divided into four groups. Rats in SHAM were given saline, and those in groups ARF, ARF-M5, and ARF-M10 were injected with glycerol (10 mL/kg) im. Concomitant and 24 hours after glycerol injection for the ARF-M5 and ARF-M10 groups, melatonin—5 mg/kg and 10 mg/kg, respectively—was administrated intraperitoneally. Forty-eight hours after the glycerol injection, kidneys of the rats were taken under anesthesia. Arginase activity, ornithine, and NO levels in the kidney tissue were determined. Melatonin had an increasing effect on kidney tissue arginase activities and ornithine levels while decreasing NO concentration. It is possible that besides the direct scavenging effect, the stimulatory effect of melatonin on arginase activity may result in an inhibition of NOS activity and, finally, a decrease in the kidney NO level.

The bronchoalveolar epithelial permeability in house painters as determined by Tc-99m DTPA aerosol scintigraphy

Purpose: Isocyanates are highly reactive chemicals used in a number of industries including paints. Therefore, house painters are known to be at risk for occupational exposure to isocyanates. Our objectives in this study were: (1) to investigate the possible effects of isocyanate exposition on the bronchoalveolar epithelial permeability in house painters by using Tc-99m DTPA radioaerosol lung scintigraphy; (2) to assess whether or not some differences exist between asthmatic and non-asthmatic house painters, and (3) to determine the relationship between Tc-99m DTPA radioaerosol lung scintigraphy and the spirometric measurements, and the work duration of house painters.Materials and Methods: Ten non-smoking house painters (28.8±8.8 yrs) and ten healthy volunteers underwent Tc-99m DTPA radioaerosol lung scintigraphy. Following inhalation of radiotracer through a nebulizer for 5 minutes, dynamic scintigrams (1 frame/min, up to 10 min) were taken from both lungs. ROIs were drawn over the both lung area, and time-activity curves were obtained, from which the half-time (T1/2) of Tc-99m DTPA clearance was calculated. Spirometric lung function test was measured in all house painters.Results: Mean T1/2 values (min±SD) were 93.74±32.79 for house painters, and 90.96±40.02 for control subjects. There was no significant difference in T1/2 values of Tc-99m DTPA clearance between house painters and controls, and between asthmatic and non-asthmatic house painters as well. No correlation was observed between T1/2 values of Tc-99m DTPA clearance and spirometric measurements. In house painters, there was a positive correlation between T1/2 values of Tc-99m DTPA clearance and work duration (r=0.73, p=0.016).Conclusions: Our findings indicate that in house painters, occupational exposure to isocyanates has no effect on bronchoal veolar epithelial permeability, and the rate of Tc-99m DTPA clearance shows no difference between asthmatic and non-asthmatic house painters. The positive correlation between the rate of Tc-99m DTPA clearance and work duration needs to be confirmed in larger cohorts.