Protective Effect of Grape Seed Extract on Doxorubicin-Induced Nephrotoxicity and Hepatotoxicity in Albino Mice

ORUC, Ertan/0000-0003-4234-8219WOS: 000284394200003The aim of this study was to evaluate the possible nephroprotective and hepatoprotective effects of grape seed extract (GSE), an antioxidant agent, against doxorubicin (DOX)-induced nephrotoxicity and hepatotoxicity in mice using biochemical and histopathological approaches. Swiss albino mice were randomly divided into six groups, each consisting of six animals: control; DOX (2.5 mg/kg body weight, 6-days cumulative dosage 15 mg/kg b. wt); GSE (50 mg/kg b. wt); GSE (150 mg/kg b. wt); GSE (50 mg/kg b. wt) + DOX; and GSE (150 mg/kg b. wt) + DOX. Serum aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen and creatinine levels were determined to assess the liver and kidney functions, respectively. Besides, the liver and kidney samples were taken for the determination of tissue malondialdehyde and glutathione levels, as well as histopathological changes in the tissues. The results indicated that DOX-induced oxidative damage caused a significant decrease in glutathione levels, but a significant increase in malondialdehyde levels of the liver and kidney tissues. Each dose of GSE provided significant protection against DOX-induced toxicity, and the strongest effect was observed at a dose of 150 mg/kg body weight. Histopathological studies showed that DOX caused some structural damages, such as vascular congestion, hepatocyte and tubular epithelial degeneration, hemorrhage, glomerular atrophy and necrosis, hyaline casts in kidney, and fibrosis in the liver and kidney. In vivo results showed that GSE extract is a potent protector against DOX-induced nephrotoxicity and hepatotoxicity

Protective Effect of Royal Jelly on Some Biochemical Parameters in Cadmium-Treated Albino Mice

ORUC, Ertan/0000-0003-4234-8219WOS: 000284394200005In the present study, the protective role of Royal Jelly (RJ) on cadmium-induced toxicity in albino mice was investigated. The mice were divided into six groups. The control group received tap water, mice of treatment groups received 2 mg/kg body weight cadmium and two different doses of RJ (100 and 250 mg/kg b. wt) for 6 weeks by oral gavage. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN) and creatinine were evaluated. In addition, histopathological changes in liver and kidneys were investigated. Serum levels of AST, ALT, ALP, BUN and creatinine in mice receiving cadmium alone significantly increased compared to the other groups (p<0.05). Treatment with RJ produced amelioration in serum biochemical indices according to cadmium group. Each dose of RJ provided protection against cadmium toxicity, and its strongest protective effect was observed at a dose of 250 mg/kg b. wt. In conclusion, RJ can act as a protector agent against cadmium-induced damages of liver and kidney.Giresun University Scientific Research Projects DepartmentGiresun UniversityThis study was supported by grants from Giresun University Scientific Research Projects Department

Investigation of the Toxic Effects of a Carbamate Insecticide Methiocarb in Allium cepa L.

WOS: 000474331300003The toxic effects of methiocarb insecticide were investigated using bulbs of Allium cepa as test material. Physiological effects were investigated with rooting percentage, root length, and weight gain; Cytogenetic effects were analyzed with micronucleus (MN), chromosomal damage and mitotic index (MI) and anatomical effects were investigated on root tip cell. Biochemical effects were investigated by measuring the malondialdehyde (MDA) levels, catalase (CAT) and superoxide dismutase (SOD) activities. For this aim, A. cepa bulbs were divided into four groups, one control, and three applications; the bulbs in the control group were treated with tap water; the bulbs in the application group were treated with 2.5 mg L-1 5.0 mg L-1 and 7.5 mg L-1 doses of methiocarb for 72 h. Methiocarb administration caused a decrease in physiological parameters compared to the control group. Methiocarb administration caused an increase in the number of MN and chromosomal damage, and a decrease in MI, besides methiocarb application caused some anatomical damages on cells of root tips. Methiocarb administration caused a dose-dependent increase in CAT and SOD activities and MDA levels compared to the control group. As a result, methiocarb caused toxic effects, and the Allium test material was found to be a useful bioindicator for monitoring these effects

QT and QTc prolongation and decreased heart rate after IV administration of levamisole hydrochloride in conscious rabbits

Intravenous doses of 2.5 mg/kg and 5.0 mg/kg of levamisole on RR, QT, QTc (corrected QT), and heart rate in conscious rabbits were evaluated. The study was performed on 14 New Zealand rabbits, 1 year old, weighing between 2.5-3 kg. The animals were assigned to 2 equal groups. Rabbits of groups I and II received via the auricular vein 2.5 mg/kg and 5 mg/kg of levamisole HCl, respectively. Alligator clips were attached to four limbs. ECG records were taken by direct writing electrocardiograph before the study and after 2, 4, 6, 8, 10, 15, and 20 min of the experiment. The QT interval was manually calculated from the beginning of Q wave to the end of T wave. The same leads (II and aVR) were selected for all QT interval measurement. The animals were not given any sedatives or anaesthetics before and during ECG recording. In group I, two rabbits had the second degree atrial block at the 2(nd) and 4(th) min after the injection, which disappeared later. Heart rates were 216-230 beats/min at min 0 and dropped to 193-210 beats/min at the 2(nd) min after the injection in both groups, and remained low throughout the study. Heart rates of both groups taken at 2, 4, 6, 8, 10, 15, and 20 min after the injection were significantly lower than the values taken at 0 min except for the values of the 15(th) min in group II. QT and QTc prolongation was noticed in both groups when compared to 0 min values. Although we have no solid data to explain the mechanism involved in bradycardia and atrial block provoked by levamisole, its use resulted in bradycardia, second-degree atrial block, and acute prolongation of QT and QTc in conscious rabbits

The effects of grape seed extract against toxicity of benzene on liver and kidney tissues of albino mice: biochemical evaluation

ORUC, Ertan/0000-0003-4234-8219WOS: 000351543800007Objective: The objective of the present study was to investigate the possible effects of grape seed extract (GSE) against benzene-induced toxicity in Swiss albino mice. Methods: The animals were randomly divided into six groups each containing six mice. Group I, treated with distilled water; Group II and III orally treated with 50 mg/kg and 150 mg/kg body weight GSE, respectively. Group IV, orally treated with 250 mg/kg body weight benzene by using feeding cannula; Group V, orally treated with 50 mg/kg body weight GSE + 250 mg/kg body weight benzene; Group VI, orally treated with 150 mg/kg body weight GSE + 250 mg/kg of body weight benzene for 50 consecutive days. At the end of experimental period all mice were sacrificed; blood, liver and kidney tissues were removed after post-mortem examination. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine levels were analyzed from serum. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were analyzed from isolated tissues. And also histopathological examinations of liver and kidney tissues were investigated. Results: Serum AST, ALT, ALP, BUN and creatinine levels were slightly increased in Group IV compared with the other tested groups (p<.05). Benzene-induced toxicity caused a significant decrease in GSH levels and a significant rise in MDA levels of liver and kidney tissues. Oral treatment with GSE significantly ameliorated the indices of hepatotoxicity, nephrotoxicity and lipid peroxidation induced by benzene. Both doses of GSE provided significant protection and the strongest effects were observed at the dose level of 150 mg/kg. Conclusion: Consequently, it was found that GSE has a significant positive effect in benzene-induced toxicity, and its GSE effect is dose dependent

Pyridine induction of cytochrome P450 1A1, iNOS and metallothionein in Syrian hamsters and protective effects of silymarin

An in vivo assessment for the protective effects of silymarin for pyridine toxicity was investigated through cytochrome P450 isoform CYP1A1 and inducible nitric oxide synthase (iNOS) activity prevention. Moreover, the effect of pyridine-induced oxidative stress on metallothionein I-II (MT), a scavenger of oxygen-derived free radicals, was investigated. Forty Syrian hamsters were allocated into 4 groups. Syrian hamsters were dosed with pyridine (400 mg/kg) intraperitoneally with and without silymarin (200 mg/kg daily by gavage) for 4 days. Pyridine induced diffuse degeneration and necrosis of the proximal and distal renal tubular cells; cloudy swelling, necrosis and hepatocellular atypia of the liver; and degenerative changes in the myocardium. The degree of pathological alterations was less severe with simultaneous silymarin application. CYP1A1, iNOS and MT expression levels were elevated in liver, kidney and heart in response to acute pyridine toxicity. Silymarin application abolished or significantly suppressed the induction of CYP1A1, iNOS and MT expressions in liver, kidney and heart of the pyridine-treated Syrian hamsters. Enhanced synthesis of MT by pyridine possibly implies a purposive cellular response to prevent damage caused by oxygen radicals. However, silymarin significantly reduced the oxidative-stress-inducing effect of pyridine as reflected by decreased synthesis of MT. These results suggest that through oxidant generation, pyridine may cause alteration of the metabolic ways, including nitric oxide-mediated CYP1A1 activity. (c) 2009 Elsevier GmbH. All rights reserved