Leptin Accelerates Endothelial Wound Healing: Role of Endothelial Nitric Oxide Synthase Expression.

BACKGROUND: The endothelium is crucial for the control of vascular homeostasis and plays a role in angiogenesis. Leptin, a protein released mainly by adipose tissue, plays a key role in the regulation of energy balance and angiogenesis. We aimed to investigate the changes of endothelial nitric oxide synthetase expression on human umbilical vein endo- thelial cells wound healing model after leptin treatment. METHODS: In this study, 5 groups were planned as Group 1: control (untreated), Group 2: treated with 0.1 ng/mL leptin, Group 3: treated with 1 ng/mL leptin, Group 4: treated with 10 ng/mL leptin, and Group 5: treated with 100 ng/mL leptin. Closure rates of wound areas were calculated by the Image J program after 24 hours of leptin treatment. The WST-1 assay was used to calculate the cell viability. Immunocytochemical analysis was performed for endothelial nitric oxide synthase expression and H-Score was calculated. RESULTS: The closure rates of wound areas were calculated as 80.24%, 89.73%, 87.40%, 90.73%, and 93.70%, respectively. When all groups treated with leptin were comparedwith the control group, there was a statistically significant difference (P < .05). The WST-1 results showed that the most increasing levels of viable cells were found in the groups treated with 0.1 ng/mL leptin and 100 ng/mL leptin when compared to the control group. H-Score values of each group were calculated as 284.8 ± 15.22, 288.6 ± 8.41, 291 ± 8.16, 295.2 ± 11.60, and 308.8 ± 4.32, respectively. The difference between the control group and the group treated with 100 ng/mL leptin was statistically significant (P < .05). CONCLUSIONS: Endothelial nitric oxide synthase expression in human umbilical vein endo- thelial cells increased depending on the leptin dose and the highest increase was in the group treated with 100 ng/mL leptin.

Anticancer activity of linalool: comparative investigation of ultrastructural changes and apoptosis in breast cancer cells.

Breast cancer is the most common cancer in women in the world. Many anticancer drugs are currently used clinically have been isolated from plant species or are based on such substances. Linalool is aromatic compounds from the monoterpene group. It is the main constituents of essential oils and show antiproliferative, antioxidant, and antiseptic properties. The aim of this study was to investigate the antiproliferativeand apoptotic, effects of linalool in MCF-7 and MDA-MB-231 human breast cancer cells. MCF-7 and MDA-MB-231 human breast cancer cells were treated with different concentrations of linalool (100, 200, 400, 600, 800, 1000 µM) at 24 h and 48 h. MTT assay for cell proliferation and Annexin V assay for apoptosis was done. The morphology of breast cancer cells was investigated by light microscope and scanning electron microscope (SEM). The study show that linalool significantly induced apoptosis in all groups as dose and time-dependent (p < .05). Linalool has apoptotic and antiproliferative properties in a concentration and time-dependent manner in breast cancer cells. The cytotoxic effects of linalool on MCF-7 and MDA-MB-231 human breast cancer cells was found to be associated with apoptotic cell death. Linalool was more effective on MCF-7 human breast cancer cells in smaller amounts.

Comparison of ultrastructural changes and the anticarcinogenic effects of thymol and carvacrol on ovarian cancer cells: which is more effective?

Ovarian cancer is the seventh most common cancer worldwide in women. Many anticancer drugs are currently used clinically have been isolated from plant species or are based on such substances. Thymol (5-methyl-2-isopropylphenol) and carvacrol are oxygenated aromatic compounds from the monoterpene group. They are the main constituents of thyme essential oil and show antiproliferative, antioxidant, and antiseptic properties. The aim of this study is to compare the antiproliferative and apoptotic effects of thymol and carvacrol on SKOV-3 ovarian cancer cell line. The cancer cells were treated with different concentrations of thymol and carvacrol (100, 200, 400, 600 µM) at 24 h and 48 h durations. The cell viability was investigated by MTT assay and analysis of apoptosis with annexin V assay was determined. The study show that thymol and carvacrol significantly induced apoptosis in all groups as dose and time-dependent (p < .05). The data in the present study demonstrated that thymol and carvacrol have apoptotic and antiproliferative properties in a concentration-dependent manner toward ovarian cancer cells. SKOV-3 cancer cell line was much more sensitive to the toxic effect of thymol than carvacrol.

In vivo application of poly-3-hydroxyoctanoate as peripheral nerve graft.

OBJECTIVE: This study aims to investigate the degree of biocompatibility and neuroregeneration of a polymer tube, poly-3-hydroxyoctanoate (PHO) in nerve gap repair. METHODS: Forty Wistar Albino male rats were randomized into two groups: autologous nerve gap repair group and PHO tube repair group. In each group, a 10-mm right sciatic nerve defect was created and reconstructed accordingly. Neuroregeneration was studied by sciatic function index (SFI), electromyography, and immunohistochemical studies on Days 7, 21, 45 and 60 of implantation. Biocompatibility was analyzed by the capsule formation around the conduit. Biodegradation was analyzed by the molecular weight loss in vivo. RESULTS: Electrophysiological and histomorphometric assessments demonstrated neuroregeneration in both groups over time. In the experimental group, a straight alignment of the Schwann cells parallel to the axons was detected. However, autologous nerve graft seems to have a superior neuroregeneration compared to PHO grafts. Minor biodegradation was observed in PHO conduit at the end of 60 d. CONCLUSIONS: Although neuroregeneration is detected in PHO grafts with minor degradation in 60 d, autologous nerve graft is found to be superior in axonal regeneration compared to PHO nerve tube grafts. PHO conduits were found to create minor inflammatory reaction in vivo, resulting in good soft tissue response.

Protective effect of apricot (Prunus armeniaca L.) on hepatic steatosis and damage induced by carbon tetrachloride in Wistar rats.

The present study was planned to investigate the protective effect of 10 % and 20 % apricot-containing feed on carbon tetrachloride (CCl4)-induced hepatic steatosis and damage. Adult male Wistar rats (n 42) were divided into six groups of seven each, as follows: control group; CCl4 group; CCl4+10 % apricot group; CCl4+20 % apricot group; 10 % apricot group; 20 % apricot group. All apricot groups were fed with 10 % or 20 % apricot-containing feed for 5 months. CCl4 injections were applied to the CCl4 groups at the dose of 1 mg/kg for 3 d at the end of 5 months. In the CCl4 group, vacuolated hepatocytes and hepatic necrosis were seen, especially in the centrilobular area. Hepatocytes showed an oedematous cytoplasmic matrix, large lipid globules and degenerated organelles. The area of liver injury was found significantly decreased with apricot feeding. Malondialdehyde and total glutathione levels and catalase, superoxide dismutase and glutathione peroxidase activities were significantly changed in the CCl4 group and indicated increased oxidative stress. Apricot feeding decreased this oxidative stress and ameliorated histological damage. We concluded that apricot feeding had beneficial effects on CCl4-induced liver steatosis and damage probably due to its antioxidant nutrient (beta-carotene and vitamin) contents and high radical-scavenging capacity. Dietary intake of apricot can reduce the risk of liver steatosis and damage caused by free radicals.

Propolis prevents the effects of chronic alcohol intake on ocular tissues.

AIM: This study is designed to investigate the protective effects of propolis in ocular tissues against chronic alcohol exposure. MATERIAL AND METHOD: Wistar albino rats were used in this study. Rats were divided into 4 groups, and each group was fed a special liquid diet which contained an equal amount of calories. The control group was fed the liquid special diet without alcohol and propolis. We added propolis (150 mg/kg) to the diet of the second group. The diet of the third group contained alcohol, the concentration of which was increased progressively. The fourth group was fed a diet including propolis and alcohol. To counterbalance caloric intake, we decreased the amount of glucose in the special liquid diet for groups 3 and 4. At the end of 30 days, the animals were sacrificed and samples were kept at -80 degrees C until evaluation. Specimens were investigated by light microscopy for morphology and morphometry. RESULTS: In the histological investigation of ocular tissues, alcohol caused an increase in thickness of the cornea and corneal epithelium compared to the control group (p < 0.05). This incremental tendency was significantly reduced by propolis, and values were very close to those of the control group (p > 0.05). Alcohol did not cause any significant alteration of rat retinal thickness. CONCLUSION: This study showed that propolis is highly effective against corneal edema secondary to chronic alcohol intake.

Protective effects of ascorbic acid on hepatotoxicity and oxidative stress caused by carbon tetrachloride in the liver of Wistar rats.

This study was planned to investigate the protective effect of l(+)-ascorbic acid (Vit C) on CCl(4)-induced hepatotoxicity and oxidative stress in the liver of Wistar rats (Rattus Norvegicus, strain Wistar). Twenty-four adult male Wistar rats were fed with standard rat chow diet for 10 days and randomly were divided into four groups of six each as follows: (1) control, (2) CCl(4), (3) "CCl(4) + Vit C", (4) Vit C groups. CCl(4) was applied to rats belonging to CCl(4) and "CCl(4) + Vit C" groups subcutaneously at 1 mg kg(-1) dose CCl(4) for 3 days. Vit C applied to "CCl(4) + Vit C" and "Vit C" group rats intraperitoneally at 300 mg kg(-1) dose for 3 days. All rats were sacrificed and livers were quickly removed on the fourth day of the experiment. MDA, total glutathione (T.GSH) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) activities were measured in the liver of all groups of rats and also serum alanine amino transferase (ALT) and aspartate amino transferase (AST) activities were detected to determine liver functions in all groups of rats. Histopathological changes were evaluated by light and transmission electron microscopes. In "CCl(4) + Vit C" group, MDA level was significantly decreased (p < 0.05) and SOD, CAT, GSH-PX activities were significantly increased (p < 0.005, 0.01, 0.05) respectively, T.GSH level was significantly increased (p < 0.005) and serum ALT and AST activities were significantly decreased (p < 0.01, 0.05), respectively, when compared with CCl(4) group. These results show that Vit C has a highly protective effect on hepatotoxicity and oxidative stress caused by CCl(4).

Beneficial effects of apricot-feeding on myocardial ischemia-reperfusion injury in rats.

The present study was undertaken to evaluate the cardio-protective potential of apricot-feeding in the ischemia-reperfusion (I/R) model of rats in vivo. Rats were divided into three groups of 12 rats each. Group 1 was fed with a standard rat chow, groups 2 and 3 were fed with a standard rat chow supplemented with 10% or 20% dried apricot during 3 months before the beginning of I/R studies. To produce I/R, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Infarct sizes were found significantly decreased in 10% (55.0 +/- 4.3%) and 20% (57.0 +/- 2.9%) apricot-fed groups compared to control group (68.7 +/- 2.0%). Light and electron microscopic evaluations of hearts also demonstrated similar beneficial effects on I/R injury in apricot-fed both groups. Total phenolic contents, DPPH radical scavenging and ferric-reducing power as in vitro antioxidant capacities of rat chows were significantly increased after supplementation with apricot for each ratio. Cu, Zn Superoxide dismutase (Cu, Zn SOD) and catalase (CAT) activities were increased, and lipid peroxidation was decreased significantly in the hearts of 20% apricot-fed group after I/R. In conclusion, we clearly demonstrated in vivo cardio-protective activity of apricot-feeding related to its antioxidant phenolic contents in rats subjected to myocardial I/R.

The beneficial effects of pentoxifylline on caerulein-induced acute pancreatitis in rats.

In this study we aimed to investigate the effect of pentoxifylline on caerulein-induced acute pancreatitis (AP) by detecting oxidative stress markers and performing histopathological examination. Twenty-one adult female Sprague-Dawley rats were divided into three groups as follows: control, caerulein, and caerulein + pentoxifylline groups. Pancreatic tissues of rats from all groups were removed for light and electron microscopic examination and determination of oxidative stress markers. Pancreatic oxidative stress markers were evaluated by the measurements of malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and total glutathione (GSH). Serum amylase and lipase levels were determined spectrophotometrically. The pancreatic damage score was significantly increased (P < 0.005) in the caerulein group, whereas it was decreased (P < 0.05) in the caerulein+ with pentoxifylline group. MDA levels, CAT, SOD, GPx, and GSH activities were significantly altered (P < 0.05, P < 0.005) in the caerulein group and indicated increased oxidative stress. Oxidative stress markers were normalized with pentoxifylline administration. Caerulein administration resulted in significant increase (P < 0.05) in amylase and lipase levels; pentoxifylline reduced the levels of these enzymes. Pentoxifylline is potentially capable of limiting pancreatic damage produced during AP by restoring the fine structure of acinar cells and tissue antioxidant enzyme activities. We concluded that pentoxifylline may have beneficial effects in the treatment of caerulein-induced AP.

Potent protective effect of apricot and beta-carotene on methotrexate-induced intestinal oxidative damage in rats.

Several studies have well confirmed the contribution of oxidative stress in the pathogenesis of methotrexate (MTX)-induced damage in the small intestine. Many agents have been tried experimentally to reduce or inhibit the oxidative stress. To our knowledge, there is no study about apricot consumption on the MTX-induced damage in the small intestine. The aim of this study was to determine the possible protective effects of apricot and beta-carotene on MTX-induced intestinal damage in rats. The rats were randomly divided into seven groups as follows; I-control group; II-apricot group; III-beta-carotene group; IV-MTX group; V-apricot+MTX group; VI-beta-carotene+MTX group and VII-apricot+beta-carotene+MTX group. In the MTX group; fusion and shortening in the villus, epithelial desquamation, crypt loss, inflammatory cell infiltration in the lamina propria, goblet cell depletion and microvillar damage were observed in the small intestine. Parallel to histological results, malondialdehyde (MDA) content and myeloperoxidase (MPO) activity were found to be increased, whereas superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GP-x) activities and glutathione (GSH) content were decreased in the MTX group. However, single or combined application of apricot and beta-carotene ameliorated all of these hazardous effects in antioxidant system in MTX-treated groups. In conclusion, our results demonstrate that apricot and/or beta-carotene treatment may protect the impairment of oxidative stress and ameliorate MTX-induced intestine damage at biochemical and histological levels.

The contradictory effects of nitric oxide in caerulein-induced acute pancreatitis in rats.

This study was planned to observe the effects of nitric oxide synthesis on the antioxidative defense enzymes and pancreatic tissue histology in caerulein-induced acute pancreatitis. Acute pancreatitis was induced by intraperitoneal injections of 50 microg/kg caerulein, L-arginine used for NO induction and N(omega)-nitro-L-arginine methyl ester (L-NAME) used for NO inhibition. In the caerulein group acinar cell degeneration, interstitial inflammation, oedema and haemorrhage were detected. Pancreatic damage scores were decreased with both NO induction and inhibition (p<0.05). MDA, GSH-Px, CAT, GSH and SOD activities were significantly changed in the caerulein group and indicated increased oxidative stress. Both NO induction and inhibition decreased this oxidative stress. It is concluded that both nitric oxide induction and inhibition ameliorated caerulein-induced acute pancreatitis. The findings indicate that a certain amount of NO production has beneficial effects in experimental acute pancreatitis, but uncontrolled over-production of NO may be detrimental.

The effect of melatonin on 7,12-dimethyl-benz[a]anthracene injury in comparison with vitamin E + selenium in mouse kidneys.

The aims of this study were to observe the changes in antioxidative defense enzymes and renal morphology after 7,12-dimethyl-benz[a]anthracene (7,12-DMBA) administration in mice and to investigate the possible protective effects of melatonin against 7,12-DMBA-induced renal damage in comparison with vitamin E + selenium (vit E + Se). Forty female mice were divided into four groups: control, DMBA, DMBA + vit E + Se and DMBA + melatonin. In the DMBA group, mice were given injections of 7,12-DMBA (20 mg/kg). DMBA + vit E + Se group mice received injections of 7,12-DMBA + vit E + Se (20 mg/kg + 90 mg/kg + 1.8 microg/kg). In the melatonin group, mice were given injections of 7,12-DMBA + melatonin (20 mg/kg + 4.2 mg/kg). The experiment lasted for 21 days. Mice were killed and the kidneys were taken for enzyme analyses and histologic examination. Catalase (CAT) and glutathione peroxidase (GSH-Px) activities were found significantly decreased in the DMBA group and in the DMBA + vit E + Se group when compared with the control group (P < 0.05), whereas CAT and GSH-Px activities were found significantly elevated in the DMBA + melatonin group when compared with the control (P < 0.05) and the DMBA group (P < 0.01). Exposure to DMBA resulted in tubular alterations in renal cortex. Morphometric analysis revealed proximal and distal tubular damage (P < 0.05). These alterations were found to be prevented by melatonin but not with vit E + Se administration. These results reveal that melatonin stimulates CAT and GSH-Px activities and prevents renal injury better than vit E + Se combination in mice kidneys.

Beneficial role of aminoguanidine on acute cardiomyopathy related to doxorubicin-treatment.

Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic that has cardiotoxicity as a major side effect. One mechanism of this toxicity is believed to involve the reactive oxygen radical species (ROS); these agents likely account for the pathophysiology of DOX-induced cardiomyopathy. Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against ROS formation. We investigated the effects of AG on DOX-induced changes in thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content. The rats were divided into four groups:1) Control; 2) DOX group; injected intraperitoneally (i.p.) with DOX 20 mg/kg in a single dose 3) AG-treated group; injected i.p. in single dose of 20 mg/kg DOX plus 100 mg/kg AG 1 h before the DOX for 3 days, 4) AG group; injected i.p. with AG 100 mg/kg for 3 days. DOX administration to control rats increased TBARS and decreased GSH levels. AG administration before DOX injection caused significant decrease in TBARS and increase in GSH levels in the heart tissue when compared with DOX only. Morphological changes, including severe myocardial fibrosis and inflammatory cell infiltration were clearly observed in the DOX-treated heart. AG reversed the DOX-induced heart damage. Therefore AG could protect the heart tissue against free radical injury. The application of AG during cancer chemotherapy may attenuate tissue damage and improve the therapeutic index of DOX.

Protective effect of oral L-arginine supplementation on cyclosporine induced nephropathy in rats.

BACKGROUND: One of the major adverse effects of long term cyclosporine A (CyA) administration is chronic nephrotoxicity. Several studies have suggested that alterations of the L-arginine (L-Arg) nitric oxide (NO) pathway may be involved in the pathogenesis of CyA-induced kidney damage. AIM: We postulated that in vivo activation of L-Arg-NO pathway might have a beneficial effect on CyA-induced renal damage. Conditions of chronic NO enhancement was established with L-Arg supplementation and chronic NO blockade with N-nitro-L-Arg methyl ester (L-NAME). We tested the hypothesis that, if CyA administration alters intrarenal NO synthesis, then exogenous L-Arg supplementation could limit renal injury, on the contrary, L-NAME, a potent competitive inhibitor of NO synthesis, could enhance CyA nephrotoxicity. Harmful effect of NO blockade indirectly supports the beneficial effect of NO in a model of CyA nephrotoxicity. METHODS: Rats were administered vehicle (VH), CyA (7.5 mg/kg/day), CyA + L-Arg (2g/kg/day), CyA + L-NAME (5 mg/100 ml/day), CyA + L-Arg + L-NAME, VH + L-Arg, VH + L-NAME and were sacrificed at the end of the experiment. Body weight, serum creatinine, blood urea nitrogen (BUN) and NO levels were determined. Tubular injury and interstitial fibrosis were evaluated semiquantitatively using scoring systems on paraffin sections stained with hematoxylin/eosin (H/E), Masson's trichromic and periodic acid-Schiff (PAS). RESULTS: The CyA group developed marked renal injury, characterized by a significant increase in serum creatinine and BUN, and histopathological alterations including tubular dilatation, vacuolization, necrosis, interstitial cell infiltration and tubulointerstitial fibrosis. CyA reduced serum NO level. L-Arg treatment significantly enhanced NO biosynthesis and protected animals from CyA-induced kidney damage. In contrast L-NAME strikingly reduced serum NO level, and worsened biochemical and histopathological alterations. CONCLUSION: Chronic CyA nephrotoxicity can be aggravated by NO blockade and ameliorated by NO enhancement suggesting that L-Arg supplementation may be protective in CyA nephrotoxicity.

Gentamicin-induced nephrotoxicity and protective effect of caffeic acid phenethyl ester in rats.

The objective of this study was to investigate the beneficial effects of caffeic acid phenethyl ester (CAPE) on gentamicin (GM)-induced nephrotoxicity in Wistar rats. Twenty-one adult Wistar rats were divided into three groups as follows: control group, GM and GM + CAPE group. Control group rats were injected with 5% ethanol, GM group rats were treated with 100 mg/kg GM and GM + CAPE group were pretreated with 10 mumol/kg CAPE for 2 days, then exposed to GM at the same dose. Drug injections were applied for 12 days. Twenty-four hours after the last injection, rats were killed and kidneys were quickly removed. Tissue malondialdehyde (MDA) measurements and microscopic examination of kidneys were performed. In the GM group, significant increases in MDA levels were observed (P < 0.05). These changes were found to be normalized in the GM + CAPE group. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules were found to be prevented by CAPE pretreatment. In conclusion, CAPE exerted an improvement on GM-induced nephrotoxicity, possibly, at least in part through inhibition of the production of oxygen free radicals that cause lipid peroxidation.

Comparison of chemopreventive effects of Vitamin E plus selenium versus melatonin in 7,12-dimethylbenz(a)anthracene-induced mouse brain damage.

In this work, the protective effect of Vitamin E plus selenium (Vit E+Se) and melatonin against 7,12-dimethylbenz(a)anthracene (7,12-DMBA)-induced changes in superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT) and carbonic anhydrase (CA) activities and malonedialdehyde (MDA) levels of mouse brain were compared. 12-month old mice were divided into four groups each including 10 animals. The first group served as control group. The second group was treated with 7,12-DMBA (20 mg/(kg day)). The third group was treated with 7,12-DMBA and Vitamin E (90 microg/(individual day)) and selenium (1.8 microg/(individual day)) simultaneously. The fourth group was treated with 7,12-DMBA and melatonin (4.2 mg/(kg day)) simultaneously. Treatment continued for 21 days after which the mice were sacrificed and brain homogenates were prepared. 7,12-DMBA treated group exhibited significantly decreased levels of brain SOD, GSHPx, CAT and CA activities and increased MDA levels as compared to control. Vitamin E+Se fully or partially restored enzyme inhibition except for SOD. Lipid peroxidation was also reduced in Vitamin E+Se treated group. Melatonin provided a better protection for SOD, GSHPx and CAT, and a plausible protection for CA activity. Protection against lipid peroxidation measured as MDA in melatonin treated group was appreciable although slightly lesser than the protection provided by Vitamin E+Se. The results imply that Vitamin E+Se and melatonin both provide chemoprevention against 7,12-DMBA-induced oxidative stress in mouse brain.

Melatonin protects against myocardial doxorubicin toxicity in rats: role of physiological concentrations.

Doxorubicin (Dox) is a widely used antineoplastic drug. Oxygen radical-induced injury of membrane lipids is considered to be the most important factor responsible for the development of Dox-induced cardiotoxicity. The pineal secretory product, melatonin, is known to be a potent free radical scavenger and its pharmacological concentrations have been shown to reduce Dox-induced cardiac damage. However, the physiological role of melatonin in the prevention of this damage is unknown. We investigated physiological and pharmacological effects of melatonin on Dox-induced changes in the levels of malondialdehyde (MDA), a lipid peroxidation product, and morphological changes in heart. Rats were pinealectomized (Px) or sham-operated (control) 2 months before the studies. Melatonin was administered [4 mg/kg, intraperitoneally (i.p.)] 1 hr before or 24 hr after the administration of a single dose of Dox (20 mg/kg, i.p.) and continued for 2 days. The levels of MDA Dox was found to be significantly higher in the Px rats (55.9 +/- 0.6 nmol/g tissue) than intact control animals (42.6 +/- 0.4). Dox administration to Px and non-Px rats significantly increased the MDA levels. Pre- and post-treatment with melatonin in both Px and intact rats significantly reduced MDA levels. Morphological changes parallelled the MDA alterations. These findings strongly suggest that both physiological and pharmacological concentrations of melatonin are important in protecting the heart from Dox-induced damage in rats. It would seem valuable to test melatonin in clinical trials for prevention of possible heart damage associated with Dox.

Carbon tetrachloride-induced nephrotoxicity and protective effect of betaine in Sprague-Dawley rats.

OBJECTIVES: To observe the changes in the antioxidative defense enzymes and to detect the alterations of renal microscopy after carbon tetrachloride (CCl4) administration in rats and to investigate the possible protective effects of betaine against CCl4-induced renal damage. METHODS: Thirty-two adult Sprague-Dawley rats were divided into four groups as follows: control group, betaine group, CCl4 group, and CCl4 + betaine group. CCl4 was given subcutaneously at 1 mL/kg. In the CCl4 + betaine group, rats were pretreated with betaine, then exposed to CCl4 at the same dose. Betaine group rats received concentrated betaine solution. The rats were killed and the kidneys taken for enzyme analyses and histologic examination. Glutathione peroxidase, superoxide dismutase, and catalase activities were measured in right kidney homogenates. Left kidneys were processed for light microscopic evaluation. RESULTS: In the CCl4-treated group, significant increases in kidney superoxide dismutase and catalase activities and significant decrease in glutathione peroxidase activity were observed (P <0.01). These changes were found to be normalized in the CCl4 + betaine group. Betaine did not change the enzyme activities. Exposure to CCl4 resulted in glomerular and tubular alterations in the renal cortex. These alterations were found to be prevented by betaine pretreatment. CONCLUSIONS: These results indicate that exposure to CCl4 leads to renal damage in rats and betaine exerts an improvement on nephrotoxic effects of CCl4.

The protective effects of physiological and pharmacological concentrations of melatonin on renal ischemia-reperfusion injury in rats.

Reactive oxygen species have been implicated in the pathophysiology of renal ischemia reperfusion (I/R) injury. The pineal secretory product melatonin is known to be a potent free radical scavenger and antioxidant. This study was designed to investigate the effects of physiological and pharmacological concentrations of melatonin on I/R injury. Rats were pinealectomized (Px) or sham-operated (control) 2 months before the I/R studies. There were eight groups of eight rats each. After a right nephrectomy to produce damage, left renal vessels were occluded for 60 min, followed by 24 h reperfusion, in rats. Malondialdehyde (MDA) levels resulting from I/R were significantly higher in the pinealectomized rats than in the control group. Melatonin administration (4 mg kg(-1) i.p. either before ischemia or reperfusion) to Px and sham-operated rats significantly reduced the MDA values and returned them to the control values. Morphological changes in the groups were similar to the MDA levels. Serum levels of blood urea nitrogen and creatine were unchanged. These results suggest that physiological and pharmacological melatonin concentrations are important for the reduction of I/R-induced damage. We also demonstrated that melatonin, even when administrated just before reperfusion, had a protective effect on I/R injury. It would seem valuable to test melatonin in clinical trials for the prevention of possible I/R injury.