Malondialdehyde Levels In Kidney Tissues Research Articles

Mitigation of hypobaric hypoxia induced renal inflammatory alterations by quercetin prophylaxis

The objective of the present study is to decipher the role of NF-κB and its associated downstream genes involved in causing inflammation in kidneys of rats under acute hypobaric hypoxia exposure. The study also aims at finding out the efficacy of quercetin in comparison with dexamethasone in prevention of hypobaric hypoxia induced renal inflammation. Sprague Dawley (SD) rats (n = 6) were preconditioned with 50 mg/Kg BW of quercetin, 1 h prior to hypobaric hypoxia exposure (12 h). The results revealed a significant increase in reactive oxygen species (ROS) generation and malondialdehyde (MDA) (p < 0.001) levels along with down regulation of GPx and SOD levels in kidney tissue of hypobaric hypoxia exposed rats as compared to control. However, ROS production and MDA levels in kidney tissues were reduced significantly (p < 0.001) with enhanced antioxidant enzyme levels (GPx and SOD) in rats fed with quercetin as compared to hypobaric hypoxia exposed control (p < 0.001). Protein expression analysis through western blotting and EMSA performed in nuclear extracts of kidneys, exhibited a significant upregulation of NF-κB under hypobaric hypoxic stress as compared to control. Whereas pretreatment with quercetin aids in downregulation of NF-κB expression in kidneys of rats as compared to the hypobaric hypoxia exposed group. Further, quercetin prophylaxis significantly reduced the expression of pro-inflammatory cytokines (TNF-α, IL-2 and IL-6), increased the anti-inflammatory cytokines (IL-10, IL-4 and TGF-β) along with reduced expression of cell adhesion molecules (ICAM-1, VCAM-1, E-selectin and P-selectin) in kidneys of rats under hypobaric hypoxia as compared to hypobaric hypoxia control. However, pre-treatment with dexamethasone was not as effective as quercetin, in controlling the renal inflammation. Furthermore, improved hematological parameters such as WBC, RBC, and platelet count indicated that quercetin is a well-functioning effective molecule under hypobaric hypoxic exposure. The histopathological and TEM findings, manifested the structural changes in tubular arrangements in kidneys of rats, and these changes were found to be modified by quercetin prophylaxis under hypobaric hypoxic stress. Hence, the present study indicates that, quercetin can be considered as a potential phytochemical flavonoid moiety in preventing the acute renal inflammation under hypobaric hypoxia.

Naringin attenuates oxidative stress, inflammation, apoptosis, and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats

Objective: To explore the possible effects of naringin on acrylamide-induced nephrotoxicity in rats. Methods: Sprague-Dawley rats weighing 200-250 g were randomly divided into five groups. The control group was given intragastric (i.g.) saline (1 mL) for 10 d. The acrylamide group was given i.g. acrylamide in saline (38.27 mg/kg titrated to 1 mL) for 10 d. The treatment groups were administered with naringin in saline (50 and 100 mg/kg, respectively) for 10 d and given i.g. acrylamide (38.27 mg/kg) 1 h after naringin injection. The naringin group was given i.g. naringin (100 mg/kg) alone for 10 d. On day 11, intracardiac blood samples were obtained from the rats when they were under anesthesia, after which they were euthanized. Urea and creatinine concentrations of blood serum samples were analyzed with an autoanalyzer. Enzyme-linked immunosorbent assay was used to quantify malondialdehyde, superoxide dismutase, glutathione, glutathione peroxidase, catalase, tumor necrosis factor-β, nuclear factor-κB, interleukin (IL)-33, IL-6, IL-1β, cyclooxygenase-2, kidney injury molecule-1, mitogen-activated protein kinase-1, and caspase-3 in kidney tissues. Renal tissues were also evaluated by histopathological and immunohistochemical examinations for 8-OHdG and Bcl-2. Results: Naringin attenuated acrylamide-induced nephrotoxicity by significantly decreasing serum urea and creatinine levels. Naringin increased superoxide dismutase, glutathione, glutathione peroxidase, and catalase activities and decreased malondialdehyde levels in kidney tissues. In addition, naringin reduced the levels of inflammatory and apoptotic parameters in kidney tissues. The histopathological assay showed that acrylamide caused histopathological changes and DNA damage, which were ameliorated by naringin. Conclusions: Naringin attenuated inflammation, apoptosis, oxidative stress, and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats.

Protective Effects of Valsartan on Gentamicin Induced Tubular Injury through Down Regulation of Urinary N-Acetyl-?-D-Glucosaminidase in Rats

Urinary N-acetyl-β-D-glucosaminidase is a marker of early tubular damage. Therefore, the current study was to investigate effects and its underling mechanisms of valsartan on gentamicin induced renal tubular injury through urinary N-acetyl-β-D-glucosaminidase parameter variety in rats. Animals were divided into four groups consisting of 12 rats each. The study lasted for 10 d. Rats were treated in two batches on the 6th and 11th d of the experiment, with 6 rats in each group. Control group rats were administered with distilled water (10 ml/kg) daily via an intragastric gavage; gentamicin group rats were given gentamicin 100 mg/kg/d intraperitoneally; valsartan (10 mg/kg/d, intragastric gavage) +gentamicin group; valsartan (20 mg/kg/d, intragastric gavage) +gentamicin group. Rats treated with gentamicin showed significant elevation in the activity and expression of urinary N-acetyl-β-D-glucosaminidase as compared with the control group; the activities of superoxide dismutase, glutathione peroxidase and catalase were lower while malondialdehyde was higher in kidney tissues; urinary protein content was not changed; serum creatinine and blood urea nitrogen were increased. Moreover, pathological damage of the renal tubules was serious in gentamicin treated rats. Valsartan significantly inhibited activity and expression of urinary N-acetyl-β-D-glucosaminidase in a dose dependent manner; dramatically increased superoxide dismutase, glutathione peroxidase and catalase activities and markedly decreased malondialdehyde levels in kidney tissues; renal tubular structural damages were also effectively ameliorated by valsartan. These results show that changes of urinary N-acetyl-β-Dglucosaminidase levels can reflect the extent of renal tubular injury, that valsartan has protective role on gentamicin-induced renal tubular injury by down-regulation urinary N-acetyl-β-D-glucosaminidase, and its down-regulation urinary N-acetyl-β-D-glucosaminidase effect may be due to its antioxidant properties in kidney tissues.

The Effect of Zinc and Melatonin Supplementation on Lipid Peroxidation of Various Tissues of Rats with by DMBA-Induced Breast Cancer

The purpose of this study was to investigate the effects of zinc and melatonin administration on lipid peroxidation in various tissues in DMBA-induced breast cancer in female rats. A total of 42 recently weaned Wistar rats were divided into 5 groups in the study: Group 1 (Control), Group 2 (DMBA Control), Group 3 (DMBA+Zinc), Group 4 (DMBA+Melatonin), Group 5 (DMBA+Melatonin, and Zinc). MDA (malondialdehyde) and GSH (glutathione) levels were determined via the spectrophotometric method in the lung, liver, spleen, pancreas, and kidney tissue samples taken from experimental animals. The highest lung, liver, spleen, pancreas, and kidney tissue MDA levels were obtained in the DMBA-induced breast cancer group control group (G2) (p&lt;0.05). MDA levels in DMBA+Zinc (G3), DMBA+Melatonin (G4), and DMBA+Melatonin and Zinc (G5) were significantly lower than group 2 (p&lt;0.05). Similarly, lung, liver, spleen, pancreas, and kidney tissue GSH levels of DMBA+Zinc (G3), DMBA+Melatonin (G4), and DMBA+Melatonin and Zinc (G5) were significantly higher than that of Group 2 (p&lt;0.05). The findings of the study indicated that increased lung, liver, spleen, pancreas, and kidney damage in DMBA-induced breast cancer is suppressed with the supplementation of zinc, melatonin, and combined zinc and melatonin.

The Effect of Giving Dadih on Malondialdehyde Levels and Renal Interstitial Fibrosis at Aging Kidney

BACKGROUND: The increase in the elderly poses problems in the areas of health, since it can cause aging of the physiological function of organs. It also has an impact on kidney function, which will enhance the chronic kidney disease. One of the theory that causes aging process is the free radical theory, which that accumulation of free radicals is caused by depletion of antioxidants. Therefore, exogenous antioxidants are needed and in this study author use dadih. Dadih is fermented buffalo milk, indigenous from West Sumatera-Indonesia. Peptides found in fermented milk contained antioxidant that can stimulate the formation of endogenous antioxidants and diversification of dadiah increases its effect as antioxidant.&#x0D; AIM: This study aims to prove the effect of dadih antioxidants on malondialdehyde (MDA) levels of kidney tissue and renal interstitial fibrosis.&#x0D; MATERIALS AND METHODS: An experimental study with post-test only control group design conducted to observe effect of dadih to kidney aging of Rattus norvegicus in the Laboratory of Andalas University. It used 30 R. norvegicus which were divided into three groups. Group K was a positive control (did not get dadih), Group P1 was given dadih 4.5 g once a day, and Group P2 was given dadih 4.5 g twice a day for 42 days. After that, MDA levels of kidney tissue are examined using the thiobarbituric acid reactive substances examination technique and examination of renal interstitial fibrosis which is done by histopathology with Sirius-red staining. Data were analyzed using the normality test with Shapiro–Wilk.&#x0D; RESULTS: The results showed that dadih can reduce levels of MDA in kidney tissue, where its decrease very significant in Group P1 (given dadih once a day) and Group P2 (given dadih twice a day) compared to the Group K (control group) 0.97 ± 0.06 pg/ml to 0.75 ± 0.03 pg/ml (p &lt; 0.05). Group P1 and Group P2 can also reduce the renal interstitial fibrosis rank. Obtained a decrease in the average fibrosis rank from Group K to Group P1 and subsequently to Group P2 (p &lt; 0.05).&#x0D; CONCLUSION: This study concluded that dadih can reduce MDA levels in kidney tissue and reduce renal interstitial fibrosis rank on aging kidney.

Effect of L/N-type Calcium Channel Blocker (Cilnidipine) on Oxidative Stress in Nitric Oxide-Deficient Hypertensive Rats

Background: The sympathetic nervous system plays a major role in the renal function through the vasoactive system and the Renin-Angiotensin-Aldosterone System. Even though interest in the renal protective effects of sympathetic blocker has been increased, there are not much data to clarify this efficiency in nitric oxide deficient hypertensive rats. Aim and Objectives: To find out the effect of cilnidipine, L/N-type calcium channel blocker on oxidative stress of kidney in nitric oxide synthase (NOS) inhibited experimental hypertensive rats. Material and Methods: Male Albino Wistar rats (n-24) were randomly allocated into four groups: group 1, control received vehicle; group 2, received Cilnidipine; group 3, received NG-nitro-L-arginine methyl ester hydrochloride (L-NAME); group 4, received L-NAME C All drugs are given orally for 4 weeks. Blood pressure was measured before and after the intervention and twice during intervention for all the rats. On the 29th day, blood was collected and animals were sacrificed and kidneys were collected. Serum and kidney tissue malondialdehyde (MDA) levels are estimated. Results: The results demonstrate that there is a significant increase in Mean Arterial Pressure (MAP) in L-NAME treated rats compared to the control group. Treatment with cilnidipine significantly decreases the MAP in group 4 rats. We also demonstrated the significantly elevated serum and kidney tissue MDA levels in L-NAME treated rat. Treatment with Cilnidipine reduced serum and kidney tissue MDA levels in group 4 rats compared to group 3 rats. Conclusion: The results demonstrate that cilnidipine has suppressive effects against progressive renal injury as evidenced by decreased oxidative stress indicator MDA levels in NO deficient hypertensive rats. This effect is explained by the L/N type calcium channel inhibition of cilnidipine, the L-type calcium channel blocking action lowers blood pressure and N-type calcium channel blocking action leads to suppression of the sympathetic nerve activity and renin-angiotensin-aldosterone system.

Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats.

The aim of this study was to evaluate the possible therapeutic or protective effects of Helichrysum plicatum DC. subsp. plicatum ethanol extract (HPE) against gentamicin-induced nephrotoxicity. Thirty-six Sprague Dawley male rats weighing between 200 and 250 g were used as live material. They were formed into six groups containing 6 rats each and were allowed to adapt to laboratory conditions for 7 d. Group I: control, 5% DMSO intraperitoneal (i.p.); Group II: HPE 100 mg/(kg·d) i.p.; Group III: HPE 200 mg/(kg·d) i.p.; Group IV: gentamicin as 80 mg/(kg·d) i.p.; Group V: gentamicin as 80 mg/(kg·d) i.p.+HPE 100 mg/(kg·d) i.p.; and Group VI: gentamicin as 80 mg/(kg·d) i.p.+HPE 200 mg/(kg·d) i.p. for 8 d. Following treatment, serum, liver, and kidney tissues were used to assess blood urea nitrogen (BUN), creatinine, enzymatic and non-enzymatic antioxidants, and lipid peroxidation. Gentamicin significantly increased serum BUN, creatinin, and liver and kidney levels of malondialdehyde (MDA). It also decreased the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Treatment with the HPE 100 mg/kg reversed gentamicin-induced alterations as evidenced by decreased serum BUN and creatinin, liver and kidney oxidant marker, and tubular necrosis as well as by an increase in antioxidant enzymes. It was found that HPE 200 mg/kg significantly increased liver and kidney tissue MDA levels in nephrotoxicity in rats. As a result, these findings support the proposition that HPE in 100 mg/kg dose demonstrates in the kidney and liver as free radicals and scavenger to prevent the toxic effects of gentamicin in both the biochemical and histopathology parameters.

Sesamin Ameliorates High-Fat Diet-Induced Dyslipidemia and Kidney Injury by Reducing Oxidative Stress.

The study explored the protective effect of sesamin against lipid-induced renal injury and hyperlipidemia in a rat model. An animal model of hyperlipidemia was established in Sprague-Dawley rats. Fifty-five adult Sprague-Dawley rats were divided into five groups. The control group was fed a standard diet, while the other four groups were fed a high-fat diet for 5 weeks to induce hyperlipidemia. Three groups received oral sesamin in doses of 40, 80, or 160 mg/(kg·day). Seven weeks later, the blood lipids, renal function, antioxidant enzyme activities, and hyperoxide levels in kidney tissues were measured. The renal pathological changes and expression levels of collagen type IV (Col-IV) and α-smooth muscle actin (α-SMA) were analyzed. The administration of sesamin improved the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, apolipoprotein-B, oxidized-low-density lipoprotein, and serum creatinine levels in hyperlipidemic rats, while it increased the high-density lipoprotein cholesterol and apolipoprotein-A levels. Sesamin reduced the excretion of 24-h urinary protein and urinary albumin and downregulated α-SMA and Col-IV expression. Moreover, sesamin ameliorated the superoxide dismutase activity and reduced malondialdehyde levels in kidney tissue. Sesamin could mediate lipid metabolism and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia.

Neutrophil gelatinase-associated lipocalin attenuates injury in the rat cecal ligation and puncture model of sepsis via apoptosis inhibition.

The aim of this study was to investigate the effect of neutrophil gelatinase-associated lipocalin (NGAL) on the rat cecal ligation and puncture (CLP)-induced sepsis and the possible mechanism. Thirty male Sprague-Dawley rats underwent CLP as sepsis models and were randomized into three groups including the sham-operated group (sham, n = 10), which only underwent a laparotomy; the sepsis group (sepsis, n = 10), which underwent CLP and subcutaneous injection of normal saline; and the sepsis + NGAL group (sepsis + NGAL, n = 10), which underwent CLP and subcutaneous injection of NGAL. Urine, blood and kidney tissue samples were collected for the determination of urine NGAL (uNGAL), plasma NGAL (pNGAL), serum creatinine (Scr), blood urea nitrogen (BUN), histomorphological and immunohistochemical examination, lipid peroxidation product malondialdehyde (MDA) and superoxide dismutase (SOD), and expression of heme oxygenase-1 (HO)-1. The levels of uNGAL, pNGAL, Scr, BUN, kidney injury score, positive TUNEL staining, activated Caspase-3 and Bax, and kidney tissue MDA levels in the sepsis group were significantly increased compared with those in the sham-operated group and the sepsis + NGAL group (P < 0.05). SOD level and HO-1 expression in sepsis + NGAL group were significantly higher than those in the sham-operated group and the sepsis group (P < 0.05). NGAL can attenuate kidney injury and apoptosis in the rat CLP model of sepsis. And the protective effect of NGAL was probably due to the inhibition of apoptosis and lipid peroxidation, and increased expression of HO-1.

Resveratrol-Dependent Down-regulation of Receptor for Advanced Glycation End-products and Oxidative Stress in Kidney of Rats With Diabetes.

Background:Millions of people in the world have diabetes mellitus and its prevalence is growing. Oxidative stress, advanced glycation end-products (AGEs) and receptor for advanced glycation end-products (RAGE) play key role in the pathogenesis of diabetes. New and safe strategies of remedy are needed for this disease.Objectives:We hypothesized that resveratrol may exert a renal protective effect on diabetic rats.Materials and Methods:Male rats with diabetes were treated with or without resveratrol as 1, 5, 10 mg/kg of body weight for 30 days. The total AGEs and malondialdehyde levels in kidney tissues were determined by spectrofluorimetric method and the insulin level was assayed using ELISA. The total antioxidant capacity contents in kidney and the glucose in plasma were measured by a colorimetric assay. The expression of RAGE was assayed in kidneys of all animals using quantitative PCR.Results:In resveratrol-treated rats with diabetes, malondialdehyde levels, plasma glucose and expression of RAGE were significantly reduced compared with the untreated group. Moreover, the total antioxidant and insulin levels significantly increased in treated rats. There was no significant difference in the AGEs contents among all the groups.Conclusions:These results revealed that resveratrol has beneficial effects on kidney by extenuating the oxidative stress and down-regulation of RAGE expression.

Antioxidant Potential of ulva rigida c. Agardh Extract: Protection from Oxidative Stress Hypothyroidism

The purpose of this study was to evaluate the effects of Ulva rigida C. Agardh, one of the green algae, on and antioxidative system in the propylthiouracil (PTU)-induced hypothyroid rats. Thirty-two rats randomly divided into four groups: control (C), control+U. rigida extract (C+UR), hypothyroid (H) and hypothyroid+U. rigida extract (H+UR). U. rigida (2%) was administered in drinking water for 5 weeks after the induction of hypothyroidism. Hypothyroid rats were under oxidative stress as reflected by icreased plasma and tissue malondialdehyde (MDA) levels. U. rigida reduced serum total cholesterol and,- triglyceride levels and plasma and heart skeletal muscle, liver and,- kidney tissue MDA levels in the H+UR group. Serum total cholesterol and tissues MDA levels were reduced in the C+UR group. Whole blood glutathione peroxidase and erythrocyte superoxide dismutase activities were increased in the H+UR and C+UR groups compared with those of te respective control groups. Paraoxonase and arylesterase activities were lower in the H group and U. rigida increased paraoxonase and arylesterase activities in C+UR and H+UR groups. We conclude that hypothyroidism is associated with oxidative stress and, U. rigida extract might have a potential use as a protective antioxidant agent in hypothroidism.

2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced hypertension

The purpose of the present study was to evaluate the effects of melatonin on biochemical and cardiovascular changes resulting from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a polychlorinated dibenzo-para-dioxin. A total of 24 Sprague-Dawley rats were divided equally into the following four groups: (1) control group was administered with 0.5mL corn oil by gavage and 0.5cc vehicle of melatonin (proportionally nine parts physiological serum+one part ethyl alcohol) intraperitoneally for 4weeks, (2) the melatonin group was given 5mg/kg/day melatonin intraperitoneally for 4 weeks, (3) the TCDD group was given 500ng/kg/day TCDD by gavage for 4 weeks and (4) the TCDD+melatonin group was given TCDD (500ng/kg/day) by gavage and melatonin (5mg/kg/day) intraperitoneally simultaneously for 4 weeks. Systolic blood pressure was evaluated by the tail-cuff method. Vascular responses to phenylephrine and acetylcholine were evaluated in the isolated thoracic aortas. TCDD not only augmented the systolic blood pressure but also increased the contractile responses to phenylephrine in aorta. Melatonin reversed the blood pressure augmented by TCDD and decreased the contractile responses to phenylephrine in aorta. TCDD induced an increase in the malondialdehyde levels in kidney tissue and melatonin did not change it. Therefore, TCDD caused a decrease in glutathione levels in kidney tissues and melatonin reversed it. Present data demonstrated that TCDD may lead to an increase in blood pressure via increased renal oxidative stress and vascular reactivity. However, melatonin might ameliorate the blood pressure disturbed by TCDD in part by decreasing the oxidant activity induced by TCDD.

Malarial Infection of Female BWF1 Lupus Mice Alters the Redox State in Kidney and Liver Tissues and Confers Protection against Lupus Nephritis

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by an imbalanced redox state and increased apoptosis. Tropical infections, particularly malaria, may confer protection against SLE. Oxidative stress is a hallmark of SLE. We have measured changes in the levels of nitric oxide (NO), hydrogen peroxide (H2O2), malondialdehyde (MDA), and reduced glutathione (GSH) in both kidney and liver tissues of female BWF1 lupus mice, an experimental model of SLE, after infection with either live or gamma-irradiated malaria. We observed a decrease in NO, H2O2, and MDA levels in kidney tissues after infection of lupus mice with live malaria. Similarly, the levels of NO and H2O2 were significantly decreased in the liver tissues of lupus mice after infection with live malaria. Conversely, GSH levels were obviously increased in both kidney and liver tissues after infection of lupus mice with either live or gamma-irradiated malaria. Liver and kidney functions were significantly altered after infection of lupus mice with live malaria. We further investigated the ultrastructural changes and detected the number of apoptotic cells in kidney and liver tissues in situ by electron microscopy and TUNEL assays. Our data reveal that infection of lupus mice with malaria confers protection against lupus nephritis.

Protective Effect of Dexpanthenol on Ischemia-Reperfusion-Induced Renal Injury in Rats

Background/Aims: This experimental study was designed to investigate protective and therapeutic effects of Dexpanthenol (Dxp), an alcoholic analogue of pantothenic acid, on kidney damage induced by ischemia-reperfusion (I/R) in rats. Methods: Forty rats were randomly divided into a control group and 4 I/R groups (1 h ischemia followed by 23 h reperfusion). Three I/R groups were treated by Dxp (500 mg/kg, i.p.) at 3 different time points (before ischemia, during ischemia and late reperfusion). The histopathological findings including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) levels were determined. Results: Kidney tissue MDA levels were found to be significantly higher in the I/R group, whereas the values of GPX were lower when compared to the control group. The levels of SOD and CAT did not reach to statistical meaning level in I/R group. Dxp given during ischemia reduced the elevated MDA levels to the nearly control levels and this ameliorating effect was found as parallel to the result of GPX. Serum levels of BUN and Cr were significantly higher in I/R group. Dxp given during ischemia significantly reduced the elevated BUN and Cr levels when compared to I/R group. Renal I/R injury also induced extensive tubular necrosis, glomerular damage and apoptosis in the histological evaluation. Dxp ameliorated these histological damages in different amounts in all treatment groups. Conclusion: In this study the protective effects of Dxp against renal I/R injury has been evaluated for the first time.

Identification of hypoglycaemic compounds from berries of Juniperus oxycedrus subsp. oxycedrus through bioactivity guided isolation technique

Ethnopharmacological relevanceDecoction of Juniperus oxycedrus subsp. oxycedrus L. (Cupressaceae) berries is used internally as tea and pounded fruits are consumed to lower blood glucose levels in Turkey. Aim of the studyTo evaluate hypoglycaemic and antidiabetic activity of J. oxycedrus subsp. oxycedrus berries and to identify active compounds through bioactivity guided isolation technique. Material and methodsHypoglycaemic effect of J. oxycedrus subsp. oxycedrus (Joso) berry extracts on oral administration was studied using in vivo models in normal, glucose-hyperglycaemic rats. Streptozotocin induced diabetic rats were used to examine antidiabetic activity of Joso extracts, subextracts, fractions, subfractions and shikimic acid (SA). ResultsThrough in vivo bioactivity-guided fractionation processes, shikimic acid, 4-O-β-d-glucopyranosyl ferulic acid and oleuropeic acid-8-O-β-d-glucopyranoside were isolated from the n-butanol subextract by silica gel and reverse phase column chromatography as the main active ingredient of the active subfraction. After 8 days administration of the major compound shikimic acid, blood glucose levels (24%), malondialdehyde levels in kidney tissues (63–64%) and liver enzymes (AST, ALT, ALP) of diabetic rats were decreased. ConclusionResults indicated that Joso berry extract and its active constituents might be beneficial for diabetes and its complications.

Protective Effects of Different Antioxidants and Amrinone on Vancomycin‐Induced Nephrotoxicity

We have studied the effects of three antioxidants and amrinone, an inotropic agent, against vancomycin-induced nephrotoxicity in rats by investigating renal function and morphology. Thirty adult female Sprague Dawley rats (168-234 g) were divided into six groups. A saline-treated group served as control. The other five groups were treated for 7 days with vancomycin alone or in combination with alpha-lipoic acid, Ginkgo biloba extract 761, melatonin or amrinone. On day 8, all the rats were sacrificed by decapitation, kidney tissues were excised immediately and blood and kidney samples were collected. Blood urea and creatinine, kidney tissue malondialdehyde levels, and kidney superoxide dismutase and glutathione (GSH) peroxidase activities were measured. The kidneys were also examined for histological changes. Vancomycin administration led to increased urea, creatinine and malondialdehyde levels and decreased superoxide dismutase and GSH peroxidase activities. Co-administration of alpha-lipoic acid, Ginkgo biloba extract, melatonin or amrinone with vancomycin prevented the increases in the urea, creatinine and melondialdehyde levels and also resulted in higher superoxide dismutase and GSH peroxidase activities. The antioxidants and AMR improved the renal pathology compared to rats treated with vancomycin alone (P<0.05). These results indicate that the three antioxidants and amrinone have potential protective effects against vancomycin-induced nephrotoxicity, which might in part be due to inhibition of free oxygen radical production. Amrinone was the most effective drug as judged on the basis of the pathological findings.

Cisplatin impairs antioxidant system and causes oxidation in rat kidney tissues: possible protective roles of natural antioxidant foods

This study aims to elucidate the molecular mechanism(s) of cisplatin nephrotoxicity and the possible protective effects of antioxidant food supplementation on this toxicity. Twenty eight rats were used throughout the study. Cisplatin was administered intraperitoneally (i.p.) in a single dose (10 mg kg(-1)). Antioxidant food supplementation was started 3 days before cisplatin treatment. In each group (control, cisplatin, cisplatin plus dried black grape and cisplatin plus tomato juice), there were seven animals. Rats were killed 72 h after treatment. The kidneys were removed and prepared for biochemical and histopathological investigations. Oxidant (sensitivity to oxidation, xanthine oxidase enzyme and malondialdehyde level) and antioxidant (superoxide dismutase, glutathione peroxidase and catalase enzymes, and antioxidant potential value) parameters were measured in kidney tissues of the groups. Histopathological examination was also performed. Significant decreases were measured in the renal activities of catalase and glutathione peroxidase enzymes. There was, however, a significant increase in the activity of xanthine oxidase enzyme in the cisplatin-treated animals compared with the control group. The kidney tissue malondialdehyde levels were found to be increased, but sensitivity to oxidation and antioxidant potential values to be decreased in the cisplatin group. In the food supplemented groups, it has been observed that black grape eliminated oxidant stress by increasing antioxidant potential, but tomato did not. Histopathological examination results also revealed significant damage in the kidney tissues from the cisplatin-treated rats. In the black grape group, significant improvements were observed compared with the cisplatin group. In the tomato group, there were also some improvements but to a lesser degree compared with the black grape group. The results suggest that cisplatin treatment causes significant oxidant load to the kidneys through both xanthine oxidase activation and impaired antioxidant defense system, which resulted in accelerated oxidation reactions in the kidney tissue. It is proposed that supplementation of some foods such as black grape which has resveratrol as an antioxidant can provide significant protection against cisplatin nephrotoxicity.

Effects of caffeic acid phenethyl ester on glycerol-induced acute renal failure in rats.

1. Free radicals and nitric oxide (NO) play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). The aim of the present study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an anti-oxidant, on the myoglobinuric ARF induced by intramuscular hypertonic glycerol injection. 2. Thirty rats were divided equally into three groups. Rats in group 1 were given saline and those in groups 2 and 3 were injected with glycerol (10 mL/kg, i.m.). Concomitant and 24 h after glycerol injection, CAPE (10 micromol/kg, i.p.) was administered to group 3 rats. Forty-eight hours after glycerol injection, blood samples and kidney tissues of rats were taken under anaesthesia. 3. Plasma concentrations of urea, creatinine, malondialdehyde (MDA) and NO were determined, as were superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities and MDA levels in kidney tissues. Kidney morphology was also investigated. 4. In the group receiving CAPE, although SOD enzyme activity was found to be increased, we failed to find any protective effect of CAPE on other parameters investigated. Moreover, although CAPE significantly decreased NO levels, it increased plasma concentrations of urea and MDA. 5. We suggest that the effect of CAPE in decreasing NO concentrations may further increase the renal ischaemia in this model. Thus, CAPE may have a worsening rather than beneficial effect under these conditions in this model of ARF.