Narin Derin

Effect of L-Carnitine on carrageenan-induced inflammation in aged rats

Background: It is known that L-carnitine is a cofactor in the transport of fatty acids across the inner mitochondrial membrane for β-oxidation. However, L-carnitine is an antioxidant compound widely used for the treatment of deficits in functions due to the aging process. Objective: The purpose of the study was to investigate the effect of L-carnitine on carrageenan-induced inflammation in aged rats. Methods:L-Carnitine (50 mg/kg/day) or control vehicle was given by gavage for 30 consecutive days to young (2-month-old) and aged (24-month old) rats. 6 ml of air was injected subcutaneously into the dorsum of each rat, followed 2 days later by 4 ml of 2% carrageenan. After 2 days, the exudate was collected from the inflamed site of each rat. The quantity of collected exudate and the number of cells which have migrated to the inflamed site were determined. Results: No differences were observed in quantity of exudate in all groups; a decrease in the number of exudate cells was established in aged rats. However, L-carnitine treatment significantly increased the number of exudate cells in both young and aged rats. The exudate cells from the aged rats exhibited a decline of both phagocytic and chemotactic activities as compared with those from the young rats, and the decreased functions were significantly enhanced by L-carnitine treatment. However, superoxide anion release was seen to be unchanged in exudate cells due to aging, and L-carnitine intake decreased the production of superoxide anion by these cells in young and aged rats. Conclusions: These findings demonstrate that L-carnitine is capable of restoring the age-related changes in the functions of inflammatory cells. Moreover, L-carnitine may play a protective role in the tissue destruction in inflammation by decreasing the superoxide anion production.

Effect of alpha-lipoic acid on visual evoked potentials in rats exposed to sulfite

This study aimed to investigate the effect of alpha-lipoic acid (LA) administration on sulfite-induced alterations in visual evoked potentials (VEPs). Fifty two male albino Wistar rats were randomized into four experimental groups as follows; control (C), LA treated (L), sodium metabisulfite (Na(2)S(2)O(5)) treated (S), Na(2)S(2)O(5)+LA treated (SL). Na(2)S(2)O(5) (260 mg/kg/day) and LA (100 mg/kg/day) were given by intragastric intubation for 5 weeks. The latencies of VEP components were significantly prolonged in the S group and returned to control levels following LA administration. Thiobarbituric acid reactive substances (TBARS) levels in the S group were significantly higher than those detected in controls. LA significantly decreased brain and retina TBARS levels in the SL group compared with the S group. Sulfite caused a significant decrease in retina and brain glutathione peroxidase (GPx) activities which was restored to control levels via LA administration. Brain glutathione (GSH):glutathione disulfide (GSSG) ratio was significantly increased in rats jointly treated with sulfite and LA compared to rats treated with sulfite alone. Though not significant, a similar increase in GSH:GSSG ratio was also observed in the retina of SL group. This study showed that LA is protective against sulfite-induced VEP alterations and oxidative stress in the brain and retina.

The effect of sulfite and chronic restraint stress on brain lipid peroxidation and anti-oxidant enzyme activities

Sulfites are used as anti-microbial and anti-oxidant agents in a variety of drugs, and function as a preservative in many food preparations. In addition to these effects, sulfites oxidize to sulfite radicals initiating lipid peroxidation. The objective of our study was to investigate the effect of restraint stress and sulfite on brain lipid peroxidation and anti-oxidant enzyme activities. Forty male Wistar rats, aged three months, were randomized to one of the following groups: control, restraint stress, sulfite-treated and restraint stress-/sulfite-treated. Chronic restraint stress was applied for 21 days (1 h/day) and sodium metabisulfite (520 mg/kg per day) was given by gavage for the same period. Lipid peroxidation was measured using the thiobarbituric acid (TBA) fluorometric assay. TBA-reactive substances (TBARS) were found increased in all treatment groups when compared to the control group. Spectrophotometric measurement of copper/zinc superoxide dismutase (Cu/Zn SOD) and catalase (CAT) revealed decreased enzyme activities in rats exposed to restraint stress compared to control and sulfite-treated rats. GSH-Px activities were significantly decreased in the restraint stress and sulfite-treated rats compared with the control rats. GSH-Px activity measured in restraint stress-/sulfite-treated rats was significantly lower than in the other groups. The presented data confirms the pro-oxidant activity of restraint stress and establishes that decreased anti-oxidant enzyme activities in restraint stress-treated rats enhances brain lipid peroxidation caused via the ingestion of sulfites.

Peritoneal macrophages function modulation by L-carnitine in aging rats

Background and aims: The aging process is associated with a progressive decline in physiological functions involving immune response in most species. The aim of the present study was to determine the effect of L-carnitine on impaired macrophages function in aged rats. Methods: Superoxide anion production, chemotaxis and phagocytic activity were studied in peritoneal macrophages obtained from young (2 months old) and aged (24 months old) rats. L-carnitine (50 mg/kg bw) or control vehicle was orally gavaged into young and aged rats for 30 consecutive days. Results: The peritoneal macrophages of the aged rats exhibited an increase in superoxide anion generation and a decline in chemotaxis and phagocytic index by comparison with the young rats. Superoxide anion production in aged rats was significantly reduced by L-carnitine treatment, as accompanied by a significant enhancement of chemotactic activity, which was restored to control levels observed in young rats. The age-related reduction in phagocytic index was only slightly, but not significantly, restored by L-carnitine administration, however. Conclusion: The findings suggest that L-carnitine administration may be useful in reversing some age-related changes.

Effects of l-carnitine on neutrophil functions in aged rats

Several age-related alterations occur at the cellular level in the immune system leading to a decrease in the immune response. The present study was designed to determine the effect of L-carnitine on impaired neutrophil functions of aged rats. For this reason, superoxide anion radical production, chemotaxis and phagocytic activity were studied in the neutrophils obtained from the peripheral blood of young and old rats. We orally gavaged L-carnitine (50 mg/kg b.w. per day) or control vehicle into young (2 months) and aged (24 months) rats for 30 consecutive days. The neutrophils of aged rats exhibited an increase in superoxide anion production and decline in phagocytosis and chemotaxis when compared with that in young rat neutrophils. Superoxide anion production in aged rats was significantly decreased by L-carnitine treatment which was accompanied with a significant enhancement of chemotactic and phagocytic activity being restored to control levels. These findings demonstrated that L-carnitine is capable of restoring the age-related changes of neutrophil functions.

Effect of aminoguanidine on visual evoked potentials (VEPs), antioxidant status and lipid peroxidation in rats exposed to chronic restraint stress

The purpose of the study was to investigate the effect of aminoguanidine (AG) on visual evoked potentials (VEPs), thiobarbituric acid reactive substances (TBARS), the activities of Cu, Zn superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), and nitrite/nitrate levels. Forty healthy male Wistar rats, aged 3 months, were divided into four equal groups: Control (C), the group treated with aminoguanidine (A), the group exposed to restraint stress (S), the group exposed to restraint stress and treated with aminoguanidine (AS). Chronic restraint stress was applied for 21 days (1 h/day) and aminoguanidine (50 mg/kg/day) was injected intraperitoneally to the A and AS groups for the same period. Aminoguanidine treatment significantly decreased retina and brain TBARS levels in rats exposed to restraint stress compared to rats exposed to restraint stress alone. Aminoguanidine treatment produced a significant decrease in brain and retina nitrite and nitrate levels with respect to the control groups. Aminoguanidine increased all antioxidant enzyme activities in both brain and retina in rats exposed to restraint stress compared to rats exposed to restraint stress alone. All VEP components were significantly decreased in AG treated rats exposed to restraint stress compared to rats exposed to restraint stress alone. Our study clearly showed that AG has the potential to prevent changes caused by stress.

Ghrelin inhibits sodium metabisulfite induced oxidative stress and apoptosis in rat gastric mucosa

This study aimed to investigate the effect of ghrelin administration on sulfite induced oxidative and apoptotic changes in rat gastric mucosa. Forty male albino Wistar rats were randomized into control (C), sodium metabisulfite (Na2S2O5) treated (S), ghrelin treated (G) and, Na2S2O5+ghrelin treated (SG) groups. Sodium metabisulfite (100 mg/kg/day) was given by gastric gavage and, ghrelin (20 μg/kg/day) was given intraperitoneally for 5 weeks. Plasma-S-sulfonate level was increased in S and SG groups. Na2S2O5 administration significantly elevated total oxidant status (TOS) levels while depleting total antioxidant status (TAS) levels in gastric mucosa. Ghrelin significantly decreased gastric TOS levels in the SG group compared with the S group. Additionally, TAS levels were found to be higher in SG group in reference to S group. Na2S2O5 administration also markedly increased the number of apoptotic cells, cleaved caspase-3 and PAR expression (PARP activity indicator) and, decreased Ki67 expression (cell proliferation index) in gastric mucosal cells. Ghrelin treatment decreased the number apoptotic cells, cytochrome C release, PAR and, caspase-3 expressions while increasing Ki67 expression in gastric mucosa exposed to Na2S2O5. In conclusion, we suggest that ghrelin treatment might ameliorate ingested-Na2S2O5 induced gastric mucosal injury stemming from apoptosis and oxidative stress in rats.

Merit of quinacrine in the decrease of ingested sulfite-induced toxic action in rat brain.

We aimed at investigating the effects of sulfite-induced lipid peroxidation and apoptosis mediated by secretory phospholipase A2 (sPLA2) on somatosensory evoked potentials (SEP) alterations in rats. Thirty male albino Wistar rats were randomized into three experimental groups as follows; control (C), sodium metabisulfite treated (S), sodium metabisulfite+quinacrine treated (SQ). Sodium metabisulfite (100 mg/kg/day) was given by gastric gavage for 5 weeks and 10 mg/kg/day quinacrine was applied as a single dose of intraperitoneal injection for the same period. The latencies of SEP components were significantly prolonged in the S group and returned to control levels following quinacrine administration. Plasma-S-sulfonate level was increased in S and SQ groups. TBARS levels in the S group were significantly higher than those detected in controls. Quinacrine significantly decreased brain TBARS levels in the SQ group compared with the S group. Quinacrine treatment did not have an effect on the increased sPLA2 level of the sulfite administered group. Immunohistochemistry showed that sulfite caused an increase in caspase-3 and TUNEL positive cells, restored to control levels via quinacrine administration. This study showed that sPLA2 might play a role in ingested sulfite-induced SEP alterations, oxidative stress, apoptotic cell death and DNA damage in the brain.

Dose-dependent effect of nutritional sulfite intake on visual evoked potentials and lipid peroxidation

The aim of this study was to clarify the dose-dependent effect of sulfite (SO₃²⁻) ingestion on brain and retina by means of electrophysiological and biochemical parameters. Fifty two male Wistar rats, aged 3 months, were randomized into four experimental groups of 13 rats as follows; control (C), sulfite treated groups (S(1); 10 mg/kg/day, S₂; 100mg/kg/day, S₃; 260 mg/kg/day). Control rats were administered distilled water, while the other three groups were given sodium metabisulfite (Na₂S₂O₅) of amounts mentioned above, via gavage for a period of 35 days. All components of visual evoked potential (VEP) were prolonged in S₂ and S₃ groups compared with S₁ and C groups. Plasma-S-sulfonate levels, which are an indicator of sulfur dioxide (SO₂) exposure, were increased in Na₂S₂O₅ treated groups in a dose-dependent manner. Furthermore, the significant increments in thiobarbituric acid reactive substances (TBARS) and 4-hydroxy-2-nonenal (4-HNE) levels occurred with increasing intake of Na₂S₂O₅. Though not significant, glutathione (GSH) and oxidized glutathione (GSSG) levels were observed to decrease with increasing doses of Na₂S₂O₅. In conclusion, Na₂S₂O₅ treatment in rats caused a dose-dependent increase in lipid peroxidation and all VEP latencies. The data indicate that lipid peroxidation could play an important role in sulfite toxicity.

CHANGES IN VISUAL EVOKED POTENTIALS, LIPID PEROXIDATION AND ANTIOXIDANT ENZYMES IN RATS EXPOSED TO RESTRAINT STRESS: EFFECT OF L-CARNITINE

The purpose of our study was to investigate the effects of L-carnitine on lipid peroxidation, Visual Evoked Potentials (VEPs) and antioxidant enzyme activities such as superoxide dismutase and catalase in rats exposed to chronic restraint stress. Forty male Wistar rats, aged three months were used. They were equally divided into four groups: control (C), the group exposed to restraint stress (R), the group treated with L-carnitine(L) and the group exposed to stress and treated with L-carnitine (RL). Chronic restraint stress was applied for 21 days (1 h/day) and L-carnitine (50 mg/kg/day) was given by gavage to the L and RL groups for the same period.Brain and retina levels of thiobarbituric acid reactive substances (TBARS) were significantly increased in the R group and were not altered in the L group compared to the C group. Brain and retina TBARS levels were lower in the RL group than in the R group. Brain and retina superoxide dismutase and catalase activities were significantly decreased in the L and R groups compared to the C group. L-carnitine pretreatment had no significant effect on superoxide dismutase and catalase activity in the RL group. All latencies of VEP components were prolonged in the R and L groups with respect to the C group. L-carnitine increased the latencies of all VEP components in the L group whereas shortened them in the RL group compared to their control groups. L-carnitine may be a promising agent for the prevention of VEP and TBARS alterations caused by stress.