Effect of sulfite on cognitive function in normal and sulfite oxidase deficient rats

Sulfites, which are commonly used as preservatives, are continuously formed in the body during metabolism of sulfur-containing amino acids. Sulfite is oxidized to sulfate ion by sulfite oxidase (SOX, EC. 1.8.3.1). The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring active avoidance learning in normal and SOX-deficient rats. For this purpose, male albino rats used in this study were divided into eight groups such as control group (C), sulfite group (25 mg/kg) (S), vitamin E group (50 mg/kg) (E), sulfite (25 mg/kg)+vitamin E group (50 mg/kg) (SE), SOX-deficient group (D), deficient+vitamin E group (50 mg/kg) (DE), deficient+sulfite group (25 mg/kg) (DS) and deficient+sulfite (25 mg/kg)+vitamin E group (50 mg/kg) (DSE). Sulfite-induced impairment of active avoidance learning in SOX-deficient rats but not in normal rats. Sulfite had no effect on hippocampus TBARS levels in SOX normal groups. In SOX-deficient rats, TBARS levels were found to be significantly increased with sulfite exposure. Vitamin E reversed the observed detrimental effects of sulfite in the SOX-deficient rats on their hippocampal TBARS but not on their active avoidance learning. In conclusion, sulfite has neurotoxic effects in sulfite oxidase deficient rats, but this effect may not depend on oxidative stress.     

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 (S₁; 10 mg/kg/day, S₂; 100 mg/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.     

Effect of sulfite on macrophage functions of normal and sulfite oxidase-deficient rats.

Sulfite has both an endogenous and an exogenous provenance in the mammalian tissues. The aim of the present study was to assess the effect of sulfite on macrophages functions in normal or sulfite oxidase deficient rats. Rats were divided into eight groups; (1) control group, (2) sulfite group (the rats received sodium meta bi-sulfite (25 mg/kg) in drinking water for 6 weeks), (3) vitamin E group (the rats received Vit E (50 mg/kg) by gavage for 6 weeks), (4) sulfite group+Vit E, (5)sulfite oxidase deficient group (the rats received high-W/Mo-deficient diet. The activity of sulfite oxidase was reduced in rats maintained on the high-W/Mo-deficient diet during the first 21 days of treatment. After the sulfite-oxidase deficiency, the rats continued to receive high-W/Mo-deficient diet for 6 weeks.), (6) sulfite+sulfite oxidase deficient group, (7) Vit E+sulfite oxidase deficient group, and (8) sulfite+Vit E+sulfite oxidase deficient group. Sulfite caused a significant increase in phagocytic and chemotactic activities of peritoneal macrophages. In sulfite-oxidase deficient rats, the increase in phagocytic and chemotactic activities in peritoneal macrophages after sulfite intake was found more than the control rats. Vit E supplementation prevented sulfite induced increase in macrophages functions. These results show that the macrophage functions are sensitive to sulfite intake. The effect of sulfite on macrophage functions may be related to reactive oxygen species. Because Vit E administration was able to modulate significantly sulfite-induced changes in the functions of peritoneal macrophages.     

Inhalation toxicology of sodium sulfite aerosols in rats

Rats were exposed to well-characterized aerosols of sodium sulfite, at levels ranging from 0.1 to about 15 mg/m³ and particle sizes of about 1 μm (mass median aerodynamic diameter). The responses of rats to breathing these aerosols for 3 days were evaluated by measurements of glycoprotein secretion rates by cultured tracheal explants from these rats, by measurement of protein, DNA, and RNA levels of lung homogenates prepared from these rats, and by quantitation of wet to dry weight ratios of right apical lung lobes from these rats. Increased rates of glycoprotein secretion were observed for tracheae from rats exposed to 5 or to 15 mg/m³ of Na₂SO₃ aerosol, and increased wet to dry weight ratios of right apical lobes were also observed after exposure to these levels, as well as after exposure to 1 mg/m³ of Na₂SO₃ aerosol. Control experiments involving exposure to a sulfate (Na₂SO₄) aerosol at 15 mg/m³ indicated that the observed effects were indeed due to exposure to the sulfite moiety. Exposure to aerosols of sodium hydroxymethane sulfonate (the product of addition of formaldehyde to sodium sulfite) aerosols (5 mg/m³) elicited less response in these assays than did exposure to sodium sulfite aerosol at the same concentration. We conclude that exposure of rats to well-characterized 1-μm aerosols of sodium sulfite at concentrations equivalent to amounts of SO₂ of about 0.2 – 2.7 ppm results in responses of the rats that may be conveniently evaluated when sensitive enough toxicological indexes are quantitated.     

Persistence of plasma S-sulfonates following exposure of rabbits to sulfite and sulfur dioxide

The kinetics of the formation and clearance of plasma S-sulfonate is presented for rabbits exposed to oral and intravenous sulfite and to inhaled SO₂. Rabbits injected with sulfite at 0.9 mmol/kg, iv, showed rapid formation of plasma exogenous S-sulfonate, half of which was cleared in approximately 1 hr. Sulfite in drinking water (8.9 or 26 μmol/ml) and atmospheric SO₂ (10 ppm) were administered to rabbits over a period of days. Plasma S-sulfonate increased progressively during exposure and then leveled off, indicating that equilibrium had been established. The rabbits were then removed from exposure and the clearance of plasma exogenous S-sulfonate measured. The pattern agreed quite closely to a single exponential rate with a half-life on the order of days. The clearance following SO₂ inhalation, however, was significantly slower (p < 0.01) than that following sulfite ingestion. The diffusibility of plasma S-sulfonate was investigated by using dialysis procedures. The results showed that the diffusibility of exogenous S-sulfonate varied depending upon its mode of formation, i.e., in vitro, in vivo via ingestion of sulfite, or in vivo via iv injection. Data gathered from both dialysis and in vivo experiments support the conclusion that plasma protein S-sulfonate is cleared rather slowly in vivo and that there is a fraction of plasma exogenous S-sulfonate (probably cysteine S-sulfonate) which is cleared much more rapidly. The presence of previously reported plasma endogenous S-sulfonate in rabbits was confirmed.     

Gastrointestinal metabolism of N-acetylcysteine in the rat, including an assay for sulfite in biological systems

The intestinal metabolism of N-acetylcysteine was studied in the rat. Isolated intestinal epithelial cells were shown to rapidly deacetylate [14C]-N-acetylcysteine to [14C]-cysteine, with slight oxidation of the latter to disulfide species. The cells did not accumulate reduced or oxidized cysteine, and N-acetylcysteine itself was not detected either free or in oxidized species intracellularly. Further metabolism of this NAC-derived cysteine to inorganic sulfite or glutathione was not detected. Following the administration of [14C]-N-acetylcysteine (50 mg/kg; 25 microCi) in vivo into the ilium, small quantities of both reduced and oxidized [14C]-N-acetylcysteine were demonstrated in hepatic portal vein plasma. [14C]-cysteine and inorganic sulfite were demonstrated as the major metabolites of N-acetylcysteine. These were present in the portal vein plasma at levels five and three times greater than the parent drug, respectively, 30 min after dosing. Additionally, [14C]-glutathione was shown to be a minor metabolite of N-acetylcysteine accumulating in portal vein plasma. These results may provide an explanation for the apparent low bioavailability of N-acetylcysteine when administered orally in humans and are discussed in terms of the origins of the protective effect of the drug in cases of paracetamol intoxication in humans.     

Ethane production and liver necrosis in rats after administration of drugs and other chemicals

Lipid peroxidation and liver necrosis due to a number of drugs and chemicals were studied. The agents were administered to control, vitamin E-deficient, and selenium-deficient rats. Vitamin E deficiency was documented by a low serum tocopherol level (0.34 mg/100 ml) and selenium deficiency by a specific activity of the selenoenzyme glutathione peroxidase in 105,000g liver supernatant which was approximately 1% of the control value. Glutathione S-transferase specific activity, measured with 1-chloro-2,4-dinitrobenzene as substrate, was doubled by selenium deficiency. Ethane production was measured as the index of in vivo lipid peroxidation. Hepatic necrosis was assessed histologically and by measuring serum glutamic-pyruvic transaminase. When no agents were administered, vitamin E-deficient rats produced more ethane than did control or selenium-deficient rats. Phenobarbital did not cause an increase in ethane production. CCl₄ (60 μl/100 g) and BrCCl₃ (5 μl/100 g) caused large ethane production and moderately severe liver necrosis. The vitamin E-deficient and selenium-deficient groups given BrCCl₃ produced more ethane than the controls but had no more severe hepatic necrosis than the controls. Thioacetamide (5 mmol/kg) and acetaminophen (3 g/kg) caused moderate to severe liver necrosis but only small ethane production. Vitamin E deficiency potentiated acetaminophen hepatotoxicity and selenium deficiency inhibited it. Iodipamide (1.5 mmol/kg) caused very large ethane production and death within hours in vitamin E-deficient rats. At a dose of 2 mmol/kg it caused severe liver necrosis in control rats but only small ethane production. This dose caused no liver necrosis in selenium-deficient rats. Acetylhydrazine (30 mg/kg) caused moderate ethane production in all groups but no liver necrosis. A single dose of ethanol (0.68 ml/100 g) led to small production of ethane in all groups. This study shows that many agents are capable of causing in vivo lipid peroxidation, but that lipid peroxidation does not always correlate with liver necrosis. Selenium deficiency is not a simple glutathione peroxidase deficiency state, as hepatic glutathione S-transferase is increased by it and it protects against acetaminophen and iodipamide hepatotoxicity.     

Pharmacokinetics,pharmacodynamics and toxicities of methotrexate in healthy and collagen‐induced arthritic rats

Methotrexate (MTX) is an anchor drug used to treat rheumatoid arthritis (RA), but responsiveness is variable in effectiveness and toxicity. Methotrexate and its polyglutamate conjugates (MTXPG_n) in red blood cells (RBC) have been associated with patient response. In the current study, 13 collagen‐induced arthritic (CIA) rats and 12 healthy rats were given subcutaneous doses of either saline or 0.3 or 1.5 mg/kg per 2 days of MTX from day 21 to 43 post‐induction. Blood samples were obtained at various times to measure MTX in plasma, and MTX and MTXPG_n in RBC. Effects on disease progression were indicated by body weight and paw size. After multiple‐doses, RBC MTX reached steady‐state (82.4 nm ) within 4 days. The MTXPG₂ and MTXPG₃ in RBC kept increasing until the end of the study, attaining 12.5 and 17.7 nm . Significant weight loss was observed after dosing with 1.5 mg/kg/2 days, whereas moderate effectiveness was observed after dosing with 0.3 mg/kg/2 days. A pharmacokinetic/pharmacodynamic/disease (PK/PD/DIS) model with indirect mechanisms and transduction components incorporating plasma MTX, RBC MTX and RBC MTXPG_n concentrations, and paw size was developed using naïve data pooling and ADAPT 5. The PK/PD in CIA rats dosed at 0.3 mg/kg/2 days were captured well by our proposed model. Methotrexate showed modest (I_maxd = 0.16) but sensitive (IC_50d = 0.712 nm ) effectiveness on paw edema. The higher dose produced toxicity. The proposed model offers improved understanding of the effects of methotrexate on rheumatoid arthritis. Copyright © 2013 John Wiley & Sons, Ltd.     

The effects of low dose aluminum on hemorheological and hematological parameters in rats

Aluminum (Al) is a nonessential element and humans are constantly exposed to Al as a result of an increase in industrialization and improving technology practices. Al toxicity can induce several clinical disorders such as neurotoxicity, gastrointestinal toxicity, hepatotoxicity, bone diseases, and anemia. This study aimed at evaluating the possible effects of short term and low dose Al exposure on hemorheological and hematological parameters in rats. Fourteen young, male Wistar albino rats were divided into two groups: 1 mg/200 g body weight of aluminum sulfate (Al₂(SO₄)₃ was injected intraperitoneally to the first group for two weeks, three times a week. The animals of the control group received only physiological saline solution during this period. At the end of the experimental period, anticoagulated blood samples were collected and hematological parameters were determined using an electronic hematology analyzer. Red blood cell (RBC) deformability and aggregation were measured using an ektacytometer (LORCA) and plasma and whole blood viscosities were determined with a Wells-Brookfield cone-plate rotational viscometer. Significant decreases in mean corpuscular volume (MCV), red blood cell (RBC) deformability at low shear stress levels, the aggregation half time (t1/2) and the amplitude (AMP) of aggregation and significant increments in whole blood viscosity (WBV) at native and 40% hematocrit (Hct) of Al-treated rats have been observed. In conclusion, low dose Al₂(SO₄)₃ exposure for a short-time may be responsible for alterations in either rheological properties of blood or hemorheological properties through a remarkable effect on RBC membrane mechanical properties .These alterations may also play an important role in the development of anemia in the Al-treated animals.     

The Role of Vitamin C,Vitamin E,and Selenium on Cadmium-Induced Renal Toxicity of Rats

The aim of this study was to determine whether vitamin C, vitamin E, and selenium have protective effects against cadmium-induced renal toxicity of rats. Vitamin C (250 mg/kg/day), vitamin E (250 mg/kg/day), and sodium selenate (0.25 mg/kg/day) were given to rats orally for 8 days. Cadmium (2 mg/kg/day CdCl₂) was given to rats intraperitoneally. Vitamin C, vitamin E, and selenium (in the same dose and time) were given 1 h prior to the administration of cadmium every day. The tissue and blood samples were taken from the rats for histological evaluation and biochemical analyses on the Day 9. Lipid peroxidation (LPO) and glutathione (GSH) determination were made in kidney tissue. In addition, urea and creatinine levels were determined in serum. The damage to the kidney tissue was moderate in the rats given cadmium. In this group, the distinctive changes in the proximal tubules were observed. Degenerative changes in kidney tissue were also observed in rats given vitamin C, vitamin E, selenium, and cadmium. LPO levels significantly increased and GSH levels decreased in kidney tissues following cadmium administration. Serum urea and creatinine levels were also increased in rats given cadmium. The administration of vitamin C, vitamin E, and selenium caused a significant decrease in LPO levels and an increase in GSH levels in the kidney of rats given cadmium. Serum urea and creatinine levels were decreased in rats given both the antioxidant and cadmium. It is concluded that vitamin C, vitamin E, and selenium showed some protective effect on the rat kidney.     

Effect of vitamin E on carbon tetrachloride-induced lipid peroxidation as demonstrated by in vivo pentane production

Pentane production by rats fed a stock diet exhibited a dose-dependent relationship with carbon tetrachloride (CCl₄) administered intraperitoneally. Total pentane produced during a 2-h test period following administration of a single dose of 30 μl CCl₄/100 g body wt. was greater by rats fed a vitamin Edeficient diet than by rats fed a diet supplemented with vitamin E. Vitamin Esupplemented rats pretreated with 30 μl CCl₄ daily for 4 days produced less pentane following administration of 60 μl CCl₄ on day 5 than did rats not pretreated with CCl₄; conversely, rats fed a vitamin E-deficient diet and similarly treated produced more pentane than did non-pretreated rats. This study confirmed that CCl₄ toxicity involves lipid peroxidation and that protection is provided by vitamin E. The usefulness in toxicological studies of monitoring pentane as an index of lipid peroxidation in vivo was shown.     

Effects of diazinon on pseudocholinesterase activity and haematological indices in rats: The protective role of Vitamin E

Diazinon (DZN) is an organophosphate insecticide has been used in agriculture and domestic for several years. Vitamin E (200mg/kg, twice a week), diazinon (10mg/kg, per day) and Vitamin E (200mg/kg, twice a week)+diazinon (10mg/kg, per day) combination were given to rats orally via gavage for 7 weeks. Pseudocholinesterase in serum and haematological indices were investigated at the end of the 1st, 4th and 7th weeks comparatively with control group. At the end of 1st, 4th and 7th weeks, statistically significant decrease of pseudocholinesterase activity in serum were detected when diazinon- and Vitamin E+diazinon-treated groups compared to control group. When diazinon- and Vitamin E+diazinon-treated groups were compared to each other there were no significant changes. When diazinon-treated group was compared to control group, body weight decreased significantly at the end of the 4th and 7th weeks. It was observed that at the end of 1st, 4th and 7th weeks, there was a statistically significance in haematological indices except mean corpuscular hemoglobin (MCH) when diazinon-treated group was compared to control group. At the end of 1st week increase of thrombocyte, at the end of the 4th week increase of hemoglobin and thrombocyte and at the end of the 7th week increase of red blood cell (RBC), hemoglobin, hematocrit, mean corpuscular hemoglobin concentration (MCHC) and thrombocyte were observed statistically significant when Vitamin E+diazinon treated group was compared with diazinon treated group. According to the present study, we conclude that Vitamin E reduces diazinon toxicity, but it does not protect completely.     

In vitro and ex vivo effects of indobufen on red blood cell deformability

Summary We have studied the effect of indobufen, a cyclo-oxygenase blocking agent which has proved useful in patients with obstructive vascular disease, on red blood cell (RBC) filterability in vitro and in a pilot study ex vivo.The addition of indobufen in vitro to blood samples from 10 healthy volunteers did not significantly modify RBC deformability.We evaluated the ex vivo effect of indobufen (200 mg bd) in 14 patients with obstructive vascular disease. A significant improvement in RBC deformability was noted on the 5th, 14th, and 28th days of treatment, 2 h after the morning dose. Acetylsalicylic acid given to 6 similar patients had no effect suggesting that the positive haemorheological effect of indobufen is probably not linked to its cyclooxygenase blocking effect.     

土鳖虫对红细胞变形性和膜成分的影响

目的 :研究土鳖虫粉对大鼠红细胞变形性和红细胞膜成分的影响。方法 :给大鼠灌胃土鳖虫粉1次 /d ,15d ,测定大鼠红细胞压积 ,红细胞变形性 ,红细胞膜的MDA、胆固醇含量和膜胆固醇 /磷脂比值。结果 :土鳖虫可降低高脂大鼠红细胞压积 ,增强红细胞变形能力并降低红细胞膜MDA、胆固醇含量和膜胆固醇 /磷脂比值。结论 :土鳖虫增强红细胞变形能力 ,这可能与其降低红细胞膜MDA、胆固醇含量和胆固醇 /磷脂有关。     

The effect of ingested sulfite on active avoidance in normal and sulfite oxidase-deficient aged rats

The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring active avoidance learning in normal and sulfite oxidase (SOX)-deficient aged rats. Twenty-four months of age Wistar rats were divided into four groups: control (C), sulfite-treated group (S), SOX-deficient group (D) and SOX-deficient?+?sulfite-treated group (DS). SOX deficiency was established by feeding rats with a low molybdenum (Mo) diet and adding 200?ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25?mg/kg) was given by gavage for six weeks. Active avoidance responses were determined by using an automated shuttle box. Hepatic SOX activity was measured to confirm SOX deficiency. The hippocampus was used for determining the activity of cyclooxygenase (COX) and caspase-3 enzymes and the level of prostaglandin E2 (PGE2) and nitrate/nitrite. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with normal rats. Sulfite did not induce impairment of active avoidance learning in SOX-deficient rats and in normal rats compared with their control groups. Sulfite had no effect on the activity of COX and caspase-3 in the hippocampus. Treatment with sulfite did not significantly increase the level of PGE2 and nitrate/nitrite in the hippocampus.     

Nitric oxide signalling is involved in diarylheptanoid‐induced increases in femoral arterial blood flow in ovariectomized rats

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Simultaneous and comprehensive in vivo analysis of cytochrome P450 activity by using a cocktail approach in rats

A cocktail approach can detect the activities of multiple cytochrome P450 (CYP) isoforms following the administration of multiple CYP‐specific substrates in a single experiment. This study aimed to develop a simultaneous and comprehensive in vivo analysis of CYP activity in rats. The rats received an oral administration of losartan (10 mg/kg) and omeprazole (40 mg/kg). Caffeine (1 mg/kg), dextromethorphan (10 mg/kg) and midazolam (10 mg/kg) were administered 15 min later. In the drug‐interaction phase, the rats were treated orally with dexamethasone (80 mg/kg) 24 h before, or with ketoconazole (10 mg/kg), fluvoxamine (100 mg kg) or fluconazole (10 mg/kg) 1 h before the administration of cocktail drugs. The concentrations of the drugs and their metabolites were determined by LC/MS/MS. Plasma concentrations of five CYP substrates and their metabolites were simultaneously evaluated after the oral drug administration. Fluvoxamine and fluconazole significantly increased the C_max and AUC of caffeine, and the AUC of omeprazole and midazolam. Dexamethasone significantly increased C_max and AUC of losartan, while it decreased the C_max of midazolam. Ketoconazole showed no significant effect on the pharmacokinetic parameters of the tested drugs. In conclusion, a cocktail approach was developed for simultaneous and comprehensive analysis of the activities of multiple CYP isoforms in rats. In this approach, the effects of inhibitors and an inducer of various CYP isoforms were examined. Although further studies are necessary to predict the effects in humans, this approach may be expected to serve as a convenient method for detecting drug–drug interactions in rats. Copyright © 2014 John Wiley & Sons, Ltd.     

Cadmium ions influence the chemiluminescence activity of murine splenocytes both in vitro and in vivo

The luminol-enhanced chemiluminescence (CL) activity of splenocytes of mice of the strain (CBA × C57Bl) F₁ was monitored after treatment with Cd²⁺ (cadmium chloride) in both in vitro and in vivo experiments. Cd²⁺ (at concentrations of 1 μM−1 mM) increased the CL reaction of the splenocytes (2 × 10⁶ cells/ml) in vitro in a dose-dependent manner, both instantaneously and after incubation for 1 h. In in vivo experiments. Cd²⁺ was administered in two ways. Following a 14-day administration of cadmium to mice in drinking water (300 mg Cd²⁺/l), the CL reaction of the splenocytes was significantly reduced. On the other hand, after i.p. administration of CdCl₂ dissolved in PBS (2 mg/kg body mass, repeated seven times during 14 days), the metabolic activity of the phagocytes was increased. From the results it follows that cadmium affects the immune system. However, its toxicity is dependent on the route of administration.     

不同剂量维生素E对糖尿病大鼠血糖的影响

目的:观察维生素E剂量与糖尿病大鼠血糖降低的关系。方法:SD大鼠分为空白对照组和实验组。实验组用链脲佐菌素制备糖尿病模型,分为无治疗组(D组),维生素E治疗1组(DE1组)(300 mg/kg),维生素E治疗2组(DE2组)(600 mg/kg),维生素E治疗3组(DE3组)(900 mg/kg)。测量各组体重、血糖和糖化血红蛋白。结果:实验组大鼠体重与空白对照组比较差异有显著性(P<0.001),但实验组各组之间比较差异无显著性(P>0.05)。实验组血糖和糖化血红蛋白均高于空白对照组(P<0.001)。在实验组之间,DE1组和D组比较差异无显著性(P>0.05),DE2组和DE3组明显低于DE1组和D组(P<0.01),同时DE3组又明显低于DE2组(P<0.05)。结论:维生素E可以有效降低糖尿病大鼠的血糖和糖化血红蛋白,同时在600～900 mg/kg范围内可能存在剂量反应关系。     

Protective effects of caffeic acid phenethyl ester, vitamin C, vitamin E and N-acetylcysteine on vancomycin-induced nephrotoxicity in rats

The objective of this study was to compare the beneficial effects of caffeic acid phenethyl ester (CAPE), vitamin C, vitamin E and N-acetylcysteine on vancomycin-induced nephrotoxicity. Thirty rats were randomly devided into six groups: (i) control; (ii) vancomycin, 200 mg/kg administrated via intraperitoneal route; (iii) vancomycin plus CAPE-vancomycin with 10 micromol/kg CAPE; (iv) vancomycin plus vitamin C-vancomycin (intraperitoneally) with 200 mg/dl vitamin C in drinking water; (v) vancomycin plus vitamin E-vancomycin with 1000 mg/kg body weight vitamin E (intramuscularly); and (vi) vancomycin plus N-acetylcysteine-vancomycin with 10 mg/kg body weight (intraperitoneally) of N-acetylcysteine. Vancomycin treatments were started 1 day after the first administrations of these agents and continued for 7 days. At the end of the experiments, catalase activity was significantly decreased by vancomycin in kidney homogenates (P < 0.05). Vitamin E, vitamin C, N-acetylcysteine and CAPE administrations decreased the blood urea nitrogen levels increased by vancomycin, although significant differences were detected only in the vitamins E and C groups (P < 0.05). Increased renal malondialdehyde and nitric oxide levels by vancomycin were significantly suppressed by agents used in the study (P < 0.05). Histopathological examination demonstrated prominent damages in the vancomycin-treated group. Vitamin E was the most beneficial agent on vancomycin-induced tubular damage, followed by vitamin C, N-acetylcysteine and CAPE treatments, respectively. The data suggest that vitamin E, as well as vitamin C, N-acetylcysteine and CAPE, could be useful for reducing the detrimental effects on vancomycin-induced toxicity in kidneys.