Melatonin ameliorates oxidative damage in hyperglycemia-induced liver injury.

PURPOSE: Melatonin (N-acetyl-5-methoxy-tryptamine) is synthesized mainly by the pineal gland and its antioxidant properties have been demonstrated both in short and long term studies. Our aim was to clarify the effects of hyperglycemia and to administer melatonin on lipid peroxidation, protein oxidation and oxidative DNA damage in rat. METHODS: Malondialdehyde (MDA), protein carbonyl (PCO) and total thiol (T-SH) levels were determined in plasma and liver tissue, glutathione (GSH) levels in erythrocyte and liver tissue, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in plasma and liver. Thirty-eight male Wistar rats were divided into four groups: 1--injected with saline (n = 8), 2--injected with melatonin (n = 10), 3--injected with STZ (65 mg/kg, i.p.) (diabetic group) (n = 10) and 4--injected with melatonin (10 mg/kg/day, i.p.) and STZ (65 mg/kg, i.p.) (n = 10) for 8 weeks (diabetic+ melatonin group). Colorimetric methods were used to determine the level of the oxidative stress markers. 8-OhdGwas measured using ELISA. RESULTS: MDA, PCO and 8-OHdG levels in the plasma and the liver homogenates of diabetic rats were higher than controls and were significantly reduced after melatonin treatment. T-SH and GSH levels in samples were markedly reduced in untreated diabetic rats compared with control rats; however, these parameters were increased in diabetic rats following melatonin treatment. CONCLUSION: Our findings showed that melatonin administration partially ameliorated oxidative damage in liver injury in STZ-induced diabetic rats. The present study suggests that melatonin functions as a potent antioxidant agent in diabetes. Melatonin, a nutritional supplement, may be a good therapeutic option for diabetic patients.

Effects of Ganoderma lucidum on obstructive jaundice-induced oxidative stress.

OBJECTIVE: Obstructive jaundice develops after occlusion of the common bile duct. Direct hyperbilirubinaemia, which occurs secondary to the condition, causes various life-threatening pathologies. Cytoprotective effects of Ganoderma lucidum (GL) have previously been shown. In this study, the effects of GL on oxidative stress and oxidant DNA damage in experimental obstructive jaundice were evaluated. METHODS: Sixty Wistar albino adult female rats were randomly divided into six weight-matched equal groups: sham group, bile duct ligated group (BDL); after sham operation 250 mg/kg/d of GL administered group, after sham operation 500 mg/kg/d of GL administered group, after bile duct ligation 250 mg/kg/d of GL administered (GL1BDL) group, and after bile duct ligation 500 mg/kg/d of GL administered (GL2BDL) group. GL polysaccharide was orally administered to the rats via gavage tube once a day for 14 days after bile duct ligation. RESULTS: The plasma malondialdehyde levels of the GL1BDL and GL2BDL groups were significantly lower than those of the BDL group (p < 0.01). The plasma 8-hydroxy-2'-deoxyguanosine levels of the GL1BDL and GL2BDL groups were significantly lower than those of the BDL group (p < 0.001). The liver tissue Cu-Zn superoxide dismutase level of the GL2BDL group was significantly higher than that of the BDL group (p < 0.05). CONCLUSION: GL protected against DNA and liver tissue damage by reducing oxidative stress in obstructive jaundice.

The effects of methylene blue on renal scarring due to pyelonephritis in rats.

The aim of this study was to evaluate the efficiency of methylene blue (MB) in preventing renal scar formation after the induction of pyelonephritis (PNP) in a rat model with delayed antimicrobial therapy. An inoculum of the K-12 strain of Escherichia coli was injected into both kidneys. Control groups received isotonic saline instead of bacterial solution. Four equal groups were then formed: the PNP group was untreated and the PNP ciprofloxacin (CIP) treated group was treated only with CIP intraperitoneally (i.p.) starting on the third day following bacterial inoculation. In the PNP (MB)-treated group, MB was given i.p., and in the PNP MB + CIP-treated group, MB + CIP were administered i.p.. In the sixth week following bacterial inoculation, all rats were sacrificed, and both kidneys of the rats in all groups were examined biochemically and histopathologically for renal scarring. Renal scar was significant in the groups treated with MB alone or MB + CIP combination compared with untreated or antibiotic only groups. Delayed treatment with antibiotics had no effect on scarring. These results suggest that the addition of MB to the delayed antibiotic therapy might be beneficial in preventing PNP-induced oxidative renal tissue damage.

Pathologic alterations detected in acute pancreatitis induced by sodium taurocholate in rats and therapeutic effects of curcumin, ciprofloxacin and metronidazole combination.

BACKGROUND AND AIMS: Secondary bacterial infections and free radical injury have been known to play an important role in the pathogenesis and clinical outcome of acute pancreatitis. Despite the therapy models developed in recent years, the mortality rate is still reported to be higher than expected. The objective of this study therefore was to investigate the effectiveness of ciprofloxacin and metronidazole combination and curcumin together in the treatment of acute pancreatitis. METHODS: Acute pancreatitis was induced in rats by sodium taurocholate (n = 60). Starting 6 h after the induction of acute pancreatitis, groups I and II were injected 200 mg/kg ciprofloxacin and 500 mg/kg metronidazole intraperitoneally every 12 h for 6 days. Groups II and III received 100 mg/kg curcumin since day 20 prior to the initiation of acute pancreatitis. On day 6, animals of all groups were killed. Blood and tissue samples were taken for biochemical, pathologic and bacteriologic examination. RESULTS: No statistical difference in the treatment groups versus the non-treatment group has been detected in the pancreatic tissue on the basis of histopathological scoring results. Prevalences of bacterial translocation were significantly lower in the treatment groups (groups I-III) than in the non-treatment group (group IV) (p < 0.001, p < 0.001, p < 0.05, respectively). Serum amylase, lipase, malon dialdehyde and nitric oxide (except for nitric oxide level in group I), levels of groups I, II and III were significantly lower than those of group IV (p < 0.05). CONCLUSIONS: The administration of ciprofloxacin and metronidazole in combination and curcumin in acute pancreatitis failed to provide a preventive effect on the occurrence of tissue injury, whereas free radical injury and prevalence of bacterial translocation were reduced significantly.

An evaluation of low molecular weight heparin and hyperbaric oxygen treatment in the prevention of intra-abdominal adhesions and wound healing.

BACKGROUND: Abdominal surgery can lead to intra-abdominal adhesions with significant morbidity and mortality. To prevent adhesions, an experimental study was planned to designate the effects of low molecular weight (LMW) heparins and hyperbaric oxygen (HBO) therapy both on the formation of adhesions and wound healing. METHODS: Thirty-eight Wistar albino rats underwent laparotomy to cause intra-abdominal adhesions by mechanical abrasion of the cecum and ethanol application. The rats were divided into 4 groups. In the control group (group 1) no further management was undertaken. Group 2 was treated by Enoxaparine Na, group 3 received HBO therapy, and group 4 was given both enoxaparine Na and HBO treatment. RESULTS: There was a statistically significant difference between the control and enoxaparine Na groups regarding adhesions. Statistically significant differences were observed between groups 1 and 4 and between groups 1 and 3 regarding the hydroxyproline content of the abdominal wounds. In the pathologic analysis of the abdominal wounds, there was no statistically significant difference between any of the groups, including the control group, regarding inflammation. Statistically significant differences were observed regarding angiogenesis between the control group and groups 3 and 4. There was also a statistically significant difference regarding fibrosis between groups 1 and 4. CONCLUSIONS: Enoxaparine Na decreased intra-abdominal adhesions, and HBO therapy had no beneficial effect on adhesions. Enoxaparine Na had no harmful effects on wound healing, and HBO therapy increased the process of wound healing.

Effects of osteoporotic cytokines in ovary-intact and ovariectomised rats with induced hyperthyroidism; is skeletal responsiveness to thyroid hormone altered in estrogen deficiency?

This experimental study was designed to examine the effects of hyperthyroidism on osteoporotic cytokines such as interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha in the physiological concentrations and in the deficiency of estrogen. We investigated the effects of thyroid hormones on cytokines and bone metabolism in L-thyroxine induced ovary-intact and ovariectomised rats, as levels of cytokines were increased in hyperthyroidism. The rats were divided into three groups. In the first group, L-thyroxine-induced hyperthyroid rats were ovariectomised (OVX), while the OVX rats were administered L-thyroxine in the second group. The third group received sham-operation. Blood samples taken from the tail vein of rats were analyzed for plasma T3, T4, TSH and serum IL-1beta, IL-6, TNFalpha, calcium (Ca), phosphorous (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (b-ALP). L-thyroxine administration increased the cytokines, ALP and b-ALP and decreased PTH, while there was no change in Ca and P. However, the ovariectomy of these rats did not change the levels of cytokines, Ca, P, PTH, ALP, and b-ALP. In ovariectomised rats, the cytokines, ALP and b-ALP increased but not Ca and P conversely, PTH decreased. L-thyroxine administration to ovariectomised rats did not change the levels of cytokines, Ca, P, PTH, ALP and b-ALP. In sham-operated rats there was no change in any of the parameters compared with initial values. Thyroid hormones may not be effective on bone metabolism in estrogen deficiency.

Osteoporotic cytokines and bone metabolism on rats with induced hyperthyroidism; changes as a result of reversal to euthyroidism.

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Raised levels of serum osteoporotic cytokines, such as interleukin (IL) -1beta, IL-6 and tumor necrosis factor (TNF)-alpha have been demonstrated previously in hyperthyroidism. These elevations are controversial and it is difficult to differentiate the contribution of thyroid hormones to the elevation of cytokines from that of the autoimmune inflammation in Graves' disease (GD) and follicular cell damage in thyroiditis. Therefore, we investigated the effect of thyroid hormones on serum IL-1beta, IL-6, TNF-alpha levels and bone metabolism on L-thyroxine induced hyperthyroid rats and changes in cytokine levels and bone metabolism on the same rats after reversal to euthyroidism. Rats were treated with L-thyroxine for 5 weeks (0.4 mg/ 100 g food). Plasma T3, T4, TSH and serum IL-1beta, IL-6, TNFalpha, Calcium (Ca), phosphorous (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), bone alkaline phosphatase (B-ALP) levels were measured and differential leucocyte counts were made initially, at the 5th week of the experiment (hyperthyroid state) and 5 weeks after quitting the administration of L-thyroxine (euthyroid state). Significant rises in serum IL-1beta, IL-6 and TNFalpha were noted in hyperthyroidism (P < 0.001). In euthyroid state, IL-15, IL-6 and TNFalpha decreased significantly, but IL-beta and TNFalpha were significantly higher than the baseline values (P < 0.05) while IL-6 levels turned back to the baseline values. Plasma T3 and T4 levels were significantly correlated with serum cytokines in hyperthyroid state while there was no correlation in euthyroid states. Ca and P levels did not differ significantly while PTH levels declined significantly in the hyperthyroid state (P < 0.05). After the reversal to the euthyroidism, there was no significant change in Ca, P and PTH levels. ALP and B-ALP increased significantly in hyperthyroidism (P < 0.001, P < 0.01) and they did not decrease in euthyroid state. The lymphocyte number and ratio in differentials increased significantly in the hyperthyroid state (P < 0.001). In euthyroidism they decreased significantly (P < 0.001) but it was significantly higher than the baseline value (P < 0.05). Our findings showed that the deleterious effect on bone metabolism in hyperthyroidism might be mediated by cytokines and the increased bone turnover in hyperthyroidism failed to decrease despite euthyroidism.