Hakan Erbas

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.

The Protective Effect of Curcumin on Ionizing Radiation-induced Cataractogenesis in Rats

OBJECTIVE The aim of the study was to determine the protective effect of curcumin against ionizing radiation-induced cataract in the lens of rats. MATERIAL AND METHODS Rats were divided into six groups. Group 1: Control, Group 2: Dimethyl sulfoxide (DMSO), Group 3: DMSO+curcumin, Group 4: Irradiation, Group 5: Irradiation+DMSO, Group 6: Irradiation+DMSO+curcumin. A 15 Gy total dose was given to 4, 5, 6 groups for radiation damage. Curcumin (100 mg/kg) was dissolved in DMSO and given by intragastric intubation for 28 days. At the end of the experiment, lenses were graded and enucleated. The lenticular activity of the antioxidant enzymes, total antioxidant and glutathione peroxidase (GSH-Px), and the malondialdehyde (MDA) were measured. RESULTS 100% Cataract was seen in the irradiation group. Cataract rate fell to 40% and was limited at grade 1 and 2 in the curcumin group. In the irradiation group, antioxidant enzyme levels were decreased, MDA levels were increased. There was an increase in antioxidant enzyme levels and a significant decrease in MDA in the group which was given curcumin. CONCLUSION Curcumin has antioxidant and radioprotective properties and is likely to be a valuable agent for protection against ionizing radiation. Hence, it may be used as an antioxidant and radioprotector against radiation-induced cataractogenesis.

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.

Effect of rosuvastatin on arginase enzyme activity and polyamine production in experimental breast cancer.

BACKGROUND Breast cancer is the most common malignant tumour of women around the world. As a key enzyme of the urea cycle, arginase leads to the formation of urea and ornithine from L-arginine. In the patients with several different cancers, arginase has been found to be higher and reported to be a useful biological marker. AIMS The aim of this study was to investigate the effect of rosuvastatin on serum and cancer tissue arginase enzyme activity, and ornithine and polyamine (putrescine, spermidine, spermine) levels. STUDY DESIGN Animal experiment. METHODS In this study, 50 male Balb/c mice were used. Erchlich acid tumour cells were injected into the subcutaneous part of their left foot. The mice were divided into five groups: healthy control group, healthy treatment, tumour control, treatment 1 and treatment 2. Then, 1 mg/kg and 20 mg/kg doses of rosuvastatin were given intraperitoneally. Serum and tissue arginase enzyme activities and tissue ornithine levels were determined spectrophotometrically. HPLC measurement of polyamines were applied. RESULTS Increased serum arginase activity and polyamine levels were significantly decreased with rosuvastatin treatment. In the tumour tissue, arginase activity and ornithine levels were significantly decreased in treatment groups compared to the tumour group. Tissue polyamine levels also decreased with rosuvastatin treatment. CONCLUSION We suggest that rosuvastatin may have some protective effects on breast cancer development as it inhibits arginase enzyme activity and ornithine levels, precursors of polyamines, and also polyamine levels. This protective effect may be through the induction of nitric oxide (NO) production via nitric oxide synthase (NOS). As a promising anticancer agent, the net effects of rosuvastatin in this mechanism should be supported with more advanced studies and new parameters.

VEGFR-1, Bcl-2, and HO-1 Ratios in Pregnant Women With Hypertension.

Backgound/Aim: Preeclampsia (PE) is a multisystem disease resulting in high maternal–fetal morbidity and mortality. The aim of the study was to investigate antiangiogenesis-associated alterations in antiapoptotic and antioxidative proteins in PE. Method: Of the 46 patients with PE, 25 (54.3%) were with gestational hypertension (GH), 12 (26%) were with mild, and 9 (19.5%) were with severe PE. The serum levels of vascular endothelial growth factor receptor 1 (VEGFR-1), heme oxygenase 1 (HO-1), and B-cell lymphoma/leukemia (Bcl-2) levels were measured by enzyme-linked immunosorbent assay. Results: In the severe PE group, the VEGFR-1 serum levels (27.3 ± 16.8 vs 13.3 ± 10.7 ng/mL, P = .023) were higher, but the Bcl-2 levels (1.5 ± 0.2 vs 2.1 ± 1.7 ng/mL, P = .047) were lower than the levels in the GH-mild PE group (P = .047). Also, VEGFR-1/Bcl-2 ratio in the severe PE group was significantly higher (P = .003) than the ratio in the GH-mild PE group. Conclusion: The Bcl-2 and HO-1 proteins seem to have important roles in the antiangiogenic environment of preeclampsia.

Breast Cyst Fluid Plasmin Activity and Its Effect on TGF-β2 Activation

There are two types of breast cyst and women with apocrine breast cyst may have a higher risk of developing breast cancer than cyst lined by flattened epithelium. Transforming growth factor-betas growth inhibitory effect on epithelial cells suggests a potential protective role in breast cancer. The aim of this study was to investigate the presence of plasmin in both breast cyst groups and the possible role of plasmin on transforming growth factor beta activation. Presence of high plasmin level may indicate its importance on activation process, but some other proteases may also involve in this activation mechanism.