The role of growth factors on hepatic damage in rats with obstructive jaundice.

In this study, we investigated the affect and the role of growth factors on liver damage. 110 Sprague-Dawley rats were divided into 11 groups: a sham group, a control group, HGF, EGF, IGF, TGF groups of irreversible jaundiced rats and a control group and HGF, EGF, IGF, and TGF groups of reversible jaundiced rats (n = 10). In the irreversible jaundiced groups, the common bile duct was explorated, double ligated, and cut. 150 µg/kg/day HGF, 5 µg/kg/day EGF, 5 µg/kg/day IGF, and 5 µg/kg/day TGF ß-1 were injected intraperitoneally after the seventh post-operative day. In the reversible jaundiced group, the common bile duct was ligated and the ligation was resolved on the seventh post-operative day. For 5 days, growth factors were injected at the same dose. Ductal proliferation scores significantly decreased after growth factor administration in the EGF-A and TGF-A groups. Furthermore, ductal proliferation was decreased in the TGF-B group. As a result of this study, HGF was effective in the irreversible jaundiced groups and ineffective in the reversible jaundice groups. EGF was effective in the reversible jaundiced groups and ineffective in the irreversible jaundiced groups. In both the irreversible jaundiced and reversible jaundiced groups, IGF was ineffective, although TGF ß-1 was effective. We believe that these results arise from the positive effects of effective doses of growth factor on liver damage.

The effects of carnosine in an experimental rat model of septic shock.

BACKGROUND: To examine the effect of carnosine on liver function and histological findings in experimental septic shock model, 24 Sprague-Dawley rats were used. MATERIAL/METHODS: Rats were divided into control, septic shock, and carnosine-treated septic shock groups. Femoral vein and artery catheterization were performed on all rats. Rats in the control group underwent laparotomy and catheterization; in the test groups, cecal ligation-perforation and bladder cannulation were added. Rats in the treatment group received a single intraperitoneal (IP) injection of 250 mg/kg carnosine 60 minutes after cecal ligation-perforation. Rats were monitored for blood pressure, heart rate, and body temperature to assess the postoperative septic response, and body fluids were replaced as necessary. At the end of 24 hours, rats were sacrificed and liver samples were collected. RESULTS: Statistically significant improvements were observed in liver function, tissue and serum MDA levels, and histological findings in rats treated with carnosine, compared to rats with untreated sepsis. HB and HCT values did not change significantly during the course of the experiment. Rats exposed to septic shock and treated with carnosine exhibited decreased sinusoidal dilatation and cellular inflammation into the portal region, compared to the sepsis group; the livers of rats in this group had near-normal histological structure. CONCLUSIONS: We conclude that carnosine may be an effective treatment for oxidative damage due to liver tissue perfusion defects in cases of septic shock.

Antioxidant effects of melatonin and coenzyme Q10 on oxidative damage caused by single-dose ochratoxin A in rat kidney.

In the study, the effects of relatively high single-dose of Ochratoxin A (OTA) and the antioxidant effects of Melatonin (Mel) and Coenzyme Q10 (CoQ10) on OTA-induced oxidative damages in rats were investigated. A total of 28 male Sprague-Dawley rats were divided into four groups of 7 rats each: Control, OTA, Mel+OTA and CoQ10+OTA groups. Malondialdehyde (MDA) levels in the plasma and glutathione (GSH) levels in whole blood were measured; kidneys (for histological inspection and for apoptosis detection by TUNEL method) and bone marrow samples (for chromosome aberration and mitotic index) were taken. The rats in the OTA group showed limited degeneration of tubular cells. In some tubules karyomegaly, desquamated cells and vacuolization were observed by light microscopy. Mel and CoQ10 treatment significantly reduced the severity of the lesions. MDA levels of the OTA group were significantly higher than the control, OTA+Mel and OTA+CoQ10 groups, while GSH levels were significantly lower than the control, OTA+Mel and OTA+CoQ10 groups. Higher incidences of apoptotic bodies were observed in the kidneys of the OTA group although OTA administration did not significantly change the incidence of apoptotic bodies when compared to the control and antioxidant administrated groups. Although the percentage of the mitotic index was lowest in the OTA group, no statistical difference was found among the groups. Additionally, OTA had no numerical and structural significant effects on chromosomes. It was observed that single-dose OTA administration caused oxidative damages in rat kidney and Mel or CoQ10 treatment appeared to ameliorate the OTA-induced tissue injuries.

Protective role of melatonin and coenzyme Q10 in ochratoxin A toxicity in rat liver and kidney.

Melatonin (MEL) and coenzyme Q10 (CoQ10) both display antioxidant and free radical scavenger properties. In the present study, the effect of MEL and CoQ10 on the oxidative stress and fibrosis induced by ochratoxin A (OTA) administration in rats was investigated. Rats were divided into five equal groups, each consisting of seven rats: (1) controls; (2) OTA-treated rats (289 microg/kg/day); (3) OTA+MEL-treated rats (289 microg/kg/day OTA + 10 mg/kg/day MEL); and (4) OTA+CoQ10-treated rats (289 microg/kg/day OTA + 1 mg/100 g/day body weight (bw) CoQ10). After 4 weeks of treatment, the level of malondialdehyde (MDA), glutathione peroxidase (GPx), and hydroxyproline (Hyp) were measured in the homogenates of liver and kidney. In the OTA-treated group, the levels of MDA and Hyp in both liver and kidney were significantly increased when compared with the levels of control, whereas GPx activities decreased. In OTA+MEL-treated rats, the levels of MDA and Hyp in both liver and kidney were significantly decreased when compared with the levels of OTA-treated rats; however; GPX activities increased. In the OTA+CoQ10-treated group, the levels of MDA and Hyp were decreased when compared with the levels of OTA-treated rats, whereas GPx activities increased. In the OTA+CoQ10-treated group, the levels of MDA, Hyp, and GPx were not significantly changed in kidney when compared with OTA-treated group. MEL has a protective effect against OTA toxicity through an inhibition of the oxidative damage and fibrosis both liver and kidney. Although CoQ10 has protective effect against OTA toxicity in liver tissue, it has no effect in kidney tissue.

Effects of vitamin E and gemfibrozil on lipid profiles, lipid peroxidation and antioxidant status in the elderly and young hyperlipidemic subjects.

OBJECTIVE: This study has dealt with the effects of gemfibrozil and vitamin E (vit E) therapies on lipoprotein levels, lipid peroxidation and antioxidant statuses of the elderly and young hyperlipidemic subjects. METHODS: This study took place in the Internal Medicine Clinic, Faculty of Medicine, Osmangazi University, Turkey between 2004-2005. This study was carried out on 99 hyperlipidemic and 40 control subjects. Subjects were divided into 2 groups; elderly hyperlipidemic (n=65) and young hyperlipidemic (n=34). In the young and elderly hyperlipidemic subjects of the first group treated only with vit E (600 mg/day) for one month. In the young and elderly hyperlipidemic subjects of the second group were treated only with gemfibrozil (600 mg/twice daily) for one month. The 2 therapies of vit E and gemfibrozil were then combined and applied to the third group of our study. Reduced glutathione (GSH), glutathione peroxidase (GPx), total cholesterol (total chol), serum low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG), vit E, malondialdehyde (MDA), superoxide dismutase (SOD) levels of the 3 groups were measured. RESULTS: In elderly hyperlipidemic therapy group: vit E groups, the post-treatment vit E levels increased. In the gemfibrozil groups, post-treatment TG level decreased whereas HDL level increased. In the vit E plus gemfibrozil groups, post-treatment TG level decreased, HDL, and vit E levels increased. In young hyperlipidemic therapy group: vit E groups, the post-treatment HDL, vit E, GSH, GPX levels increased whereas LDL, MDA, levels decreased. In the gemfibrozil groups, post-treatment TG, LDL decreased, HDL level increased. In the vit E plus gemfibrozil groups, post-treatment TG, LDL, MDA levels decreased whereas HDL, vit E, GSH levels increased. CONCLUSION: When combined, gemfibrozil and vit E are effective in preventing cardiovascular diseases.