Protective Effects of Curcumin against Fluoride-Induced Oxidative Stress in the Rat Brain

We examined effects of a plant polyphenolic compound, curcumin, against fluoride-induced oxidative stress in the rat brain. Five experimental groups of male rats (10 animals each) were compared. Animals of these experimental groups were treated with curcumin (10 and 20 mg/kg body mass), vitamin C (10 mg/kg), and sample solvent (0.5 ml) for a week prior to sodium fluoride intoxication. After treatment, rats of the experimental groups, except for the normal control group, were intoxicated with sodium fluoride (600 ppm through drinking water) for a week. Then, brains were collected and homogenized, and activities of superoxide dismutase and catalase and levels of reduced glutathione and lipid peroxidation final products were evaluated in the brain tissue homogenates. Treatment with curcumin prior to fluoride intoxication significantly normalized the above biochemical parameters; the intensity of protective effects of 20 mg/kg curcumin was close to that of vitamin C.     

Inhibition of potassium bromate-induced renal oxidative stress and hyperproliferative response by Nymphaea alba in Wistar rats

KBrO3-mediated renal injury and hyperproliferative response in Wistar rats. In this communication, we report the efficacy of Nymphaea alba on KBrO3 (125 mg/kg body weight, intraperitoneally) caused reduction in renal glutathione content, renal antioxidant enzymes and phase-II metabolising enzymes with enhancement in xanthine oxidase, lipid peroxidation, gamma-glutamyl transpeptidase and hydrogen peroxide (H202). It also induced blood urea nitrogen, serum creatinine and tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and DNA synthesis. Treatment of rats with Nymphaea alba (100 and 200 mg/kg body weight) one hour before KBrO3 (125 mg/kg body weight, i.p.) resulted in significant decreases in xanthine oxidase (P < 0.05), lipid peroxidation, gamma-glutamyl transpeptidase, H202 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Renal glutathione content, glutathione metabolizing enzymes and antioxidant enzymes were also recovered to significant levels (P < 0.001). These results show that Nymphaea alba acts as chemopreventive agent against KBrO3-mediated renal injury and hyperproliferative response.     

Antioxidant-rich date palm fruit extract inhibits oxidative stress and nephrotoxicity induced by dimethoate in rat

Recent investigations have proved the crucial role of nutritional antioxidants to prevent the damage caused by toxic compounds. In this study, the antioxidant effect of date palm fruit extract on dimethoate-induced oxidative stress and nephrotoxicity in rat is investigated and compared with the effect of the well-known antioxidant vitamin C. Male Wistar rats were randomly divided into six groups of ten each: a control group (C), a group that received dimethoate (20 mg/kg body weight) (D), a group given Deglet Nour extract (DNE), a group treated with DNE 30 min before the administration of dimethoate (DNE + D), a group which received VitC (100 mg/kg body weight) plus dimethoate (Vit C + D), and a group given dimethoate for the first month and DNE 30 min after administration of dimethoate, during the second month (D + DNE). These components were daily administered by gavage for 2 months. After completing the treatment period, blood samples from rats were collected under inhaled diethyl ether anesthesia for serum urea, uric acid, and creatinine levels, while the rat kidneys were obtained for enzyme assays and histology. Oral administration of dimethoate in rats induced a marked renal failure characterized by a significant increase in serum creatinine and urea levels (p < 0.01) in addition to a significant decrease in serum uric acid (p < 0.05). Interestingly, these drastic modifications were accompanied by a marked enhancement of lipid peroxidation in kidney, indicating a significant induction of oxidative damage (p < 0.01) and dysfunctions of enzymatic antioxidant defenses. These biochemical alterations were also accompanied by histological changes in kidney revealed by a narrowed Bowman’s space, tubular degeneration, tubular cell desquamation, and tubular dilatation of proximal tubules. Treatment with date palm fruit extract (Deglet Nour) and also with vitamin C significantly (p < 0.05) reversed the serum renal markers to their near-normal levels when compared with dimethoate-treated rats. In addition, Deglet Nour extract and vitamin C significantly reduced lipid peroxidation, restored the antioxidant defense enzymes in the kidney, and improved the histopathology changes. The present findings indicate that in vivo date palm fruit may be useful for the prevention of oxidative stress-induced nephrotoxicity.     

Induction of renal oxidative stress and cell proliferation response by ferric nitrilotriacetate (Fe-NTA): diminution by soy isoflavones

Ferric nitrilotriacetate (Fe-NTA) is a known potent nephrotoxic agent. In this communication, we report the chemopreventive effect of soy isoflavones on renal oxidative stress, toxicity and cell proliferation response in Wistar rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances gamma-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. Fe-NTA treatment also induced tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. A sharp elevation in the levels of blood urea nitrogen and serum creatinine has also been observed. Treatment of rats orally with soy isoflavones (5 mg/kg body weight and 10 mg/kg body weight) resulted in significant decreases in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Renal glutathione content (P < 0.01), glutathione metabolizing enzymes (P < 0.001) and antioxidant enzymes were also returned to normal levels (P < 0.001). Thus, our data suggest that soy isoflavones may be used as an effective chemopreventive agent against Fe-NTA-mediated renal oxidative stress, toxicity and cell proliferation response in Wistar rats.     

Beneficial role of naringin, a flavanoid on nickel induced nephrotoxicity in rats

This study was conducted to investigate the beneficial role of naringin on nickel induced nephrotoxicity. Nickel (Ni) (20 mg/kg body weight (b.w.) was administered intraperitoneally (i.p.) for 20 days. Naringin was administered orally (20, 40 and 80 mg/kg b.w.) with i.p. administration of Ni. Ni administration increased the levels of serum urea, uric acid and creatinine with a significant decrease in creatinine clearance and decreased levels of urea, uric acid and creatinine in urine. The levels of lipid peroxidation markers and nickel concentration in blood and kidney were also increased. While, the activities of enzymic and non-enzymic antioxidants were decreased. Treatment with naringin attenuated the alterations in the renal and urine markers, decreasing lipid peroxidation markers, increasing the antioxidant cascade and decreasing the nickel concentration in blood and kidney. All these changes were supported by histopathological observations. These findings demonstrate that naringin exerts a protective effect against nickel toxicity.     

Protective effect of coenzyme Q10 in simvastatin and gemfibrozil induced rhabdomyolysis in rats

Administration of simvastatin (80 mg/kg, po. evening dose) and gemfibrozil (600 mg/kg, po twice) for 30 days produced significant decrease in the level of reduced glutathione, superoxide dismutase, catalase and increase in the level of lipid peroxidation and various serum parameters (creatine phosphokinase, lactate dehydrogenase, serum glutamate oxaloacetate transaminase, creatinine, urea and blood urea nitrogen). This suggested involvement of oxidative stress in rhabdomyolysis. Increase in the level of reduced glutathione, superoxide dismutase, catalase and decrease in the level of lipid peroxidation and serum parameters after administration of antioxidant CoQ10 (10 mg/kg.ip) proved the protective effect of CoQ10 in rhabdomyolysis.     

Regulation of expression of antioxidant enzymes by vitamin E and curcumin in <Emphasis Type="SmallCaps">l</Emphasis>-thyroxine-induced oxidative stress in rat renal cortex

The present study investigates the antioxidative effects of vitamin E and curcumin against l-thyroxine (T₄)-induced oxidative stress in renal cortex of adult male rats. Rats were made hyperthyroid by administration of l-thyroxine (0.0012%) in their drinking water for 30 days. Vitamin E (200 mg/kg body weight/day) and curcumin (30 mg/kg body weight/day) were supplemented singly or in combination orally for 30 days along with l-thyroxine treatment. The elevated level of oxidative stress parameters (lipid peroxidation and protein carbonylation) and decline level of small antioxidant molecules (reduced glutathione and ascorbic acid) in renal cortex of T₄-treated rats were restored back by supplementation of vitamin E or/and curcumin. Increased superoxide dismutase and catalase activities in kidney cortex of T₄-treated rats were ameliorated in response to vitamin E or/and curcumin treatment. The elevated translated product of Cu/Zn-SOD, Mn-SOD and catalase in T₄-treated rats were differentially reduced by the administration of vitamin E and curcumin independently or in combination. Cu/Zn-SOD expression was ameliorated by both vitamin E and curcumin independently or in combination, whereas Mn-SOD expression was ameliorated by the supplementation of vitamin E or curcumin independently. However, the expression of catalase was alleviated by only supplementation of vitamin E to T₄-treated rats. The results suggest that both vitamin E and curcumin may play an important role in protecting T₄-induced oxidative stress in rat renal cortex by differentially modulating the activities of antioxidant enzymes and oxidative stress parameters.     

Supplementation of curcumin and vitamin E enhances oxidative stress,but restores hepatic histoarchitecture in hypothyroid rats

AimsIn the present study, the effects of vitamin E and curcumin on hepatic dysfunction, mitochondrial oxygen consumption as well as hyperlipidemia in hypothyroid rats are reported.Main methodsAdult male rats were rendered hypothyroid by administration of 0.05% 6-n-propyl-2-thiouracil (PTU) in their drinking water, while vitamin E (200 mg/kg body weight) and curcumin (30 mg/kg body weight) were supplemented orally for 30 days.Key findingsHypothyroidism-induced elevation in serum aspartate aminotransferase activity was found to decline in vitamin E and curcumin treated rats. Nevertheless, distorted histoarchitecture revealed in hypothyroid rat liver was alleviated to normal by vitamin E and curcumin treatment. Regulation of hypothyroidism induced decrease in complexes I and II mediated mitochondrial respiration by vitamin E and curcumin was found to be different. Administration of curcumin to hypothyroid rats alleviates the decreased state 4 respiration and increased respiratory control ratio (RCR) level in complex I mediated mitochondrial oxygen consumption, whereas complex II mediated respiration was not influenced by exogenous antioxidants. Although, increase in serum concentration of total cholesterol was not modified by exogenous antioxidants, increased level of non-high-density lipoprotein cholesterol (non-HDL-C) in serum of hypothyroid rats was further enhanced by vitamin E and curcumin. Moreover, a significant elevation in mitochondrial lipid peroxidation and protein carbonylation was noticed in hypothyroid groups treated with vitamin E and curcumin.SignificanceThe present study suggests that supplementation of curcumin and vitamin E enhances oxidative stress parameters and hyperlipidemia; nevertheless, it protects hypothyroid-induced altered rectal temperature, serum transaminase activity and hepatic histoarchitecture.     

Taurine plays a beneficial role against cadmium-induced oxidative renal dysfunction

The present study has been carried out to investigate the role of taurine (2-aminoethanesulfonic acid), a conditionally essential amino acid, in ameliorating cadmium-induced renal dysfunctions in mice. Cadmium chloride (CdCl₂) has been selected as the source of cadmium. Intraperitoneal administration of CdCl₂ (at a dose of 4 mg/kg body weight for 3 days) caused significant accumulation of cadmium in renal tissues and lessened kidney weight to body weight ratio. Cadmium administration reduced intracellular ferric reducing/antioxidant power (FRAP) of renal tissues. Levels of serum marker enzymes related to renal damage, creatinine and urea nitrogen (UN) have been elevated due to cadmium toxicity. Cadmium exposure diminished the activities of enzymatic antioxidants, superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PD) as well as non-enzymatic antioxidant, reduced glutathione (GSH) and total thiols. On the other hand, the levels of oxidized glutathione (GSSG), lipid peroxidation, protein carbonylation, DNA fragmentation, concentration of superoxide radicals and activities of cytochrome P450 enzymes (CYP P450s) have been found to increase due to cadmium intoxication. Treatment with taurine (at a dose of 100 mg/kg body weight for 5 days) before cadmium intoxication prevented the toxin-induced oxidative impairments in renal tissues. The beneficial role of taurine against cadmium-induced renal damage was supported from histological examination of renal segments. Vitamin C, a well-established antioxidant was used as the positive control in the study. Experimental evidence suggests that both taurine and vitamin C provide antioxidant defense against cadmium-induced renal oxidative injury. Combining all, results suggest that taurine protects murine kidneys against cadmium-induced oxidative impairments, probably via its antioxidative property.     

Attenuation of potassium bromate-induced nephrotoxicity by coumarin (1,2-benzopyrone) in Wistar rats: chemoprevention against free radical-mediated renal oxidative stress and tumor promotion response

We report the modulatory effect of coumarin (1,2-benzopyrone) on potassium bromate (KBrO(3)) mediated nephrotoxicity in Wistar rats. KBrO(3) (125 mg/kg body weight, i.p.) enhances gamma-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H(2)O(2)) generation with reduction in renal glutathione content and antioxidant enzymes. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and [(3)H]-thymidine incorporation into renal DNA. Treatment of rats orally with coumarin (10 mg/kg body weight and 20 mg/kg body weight) resulted in a significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H(2)O(2) generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Renal glutathione content (P < 0.01) and antioxidant enzymes were also recovered to significant level (P < 0.001). These results show that coumarin may be used as an effective chemopreventive agent against KBrO(3)-mediated renal oxidative stress, toxicity and tumor promotion response in Wistar rats.     

Tenoxicam Modulates Antioxidant Redox System and Lipid Peroxidation in Rat Brain

We investigated effects of two doses of Tenoxicam, a type 2 cyclooxygenase inhibitor, administration on lipid peroxidation and antioxidant redox system in cortex of the brain in rats. Twenty-two male Wistar rats were randomly divided into three groups. First group was used as control. 10 and 20 mg/kg body weight Tenoxicam were intramuscularly administrated to rats constituting the second and third groups for 10 days, respectively. Both dose of Tenoxicam administration resulted in significant increase in the glutathione peroxidase activity, reduced glutathione and vitamins C and E of cortex of the brain. The lipid peroxidation levels in the cortex of the brain were significantly decreased by the administration. Vitamin A and β-carotene concentration was not affected by the administration. There was no statistical difference in all values between 10 and 20 mg Tenoxicam administrated groups. In conclusion, treatment of brain with 10 and 20 mg Tenoxicam has protective effects on the oxidative stress by inhibiting free radical and supporting antioxidant redox system.     

Silibinin ameliorates arsenic induced nephrotoxicity by abrogation of oxidative stress, inflammation and apoptosis in rats

Arsenic (As) is an environmental and industrial pollutant that affects various organs in human and experimental animals. Silibinin is a naturally occurring plant bioflavonoid found in the milk thistle of Silybum marianum, which has been reported to have a wide range of pharmacological properties. A body of evidence has accumulated implicating the free radical generation with subsequent oxidative stress in the biochemical and molecular mechanisms of As toxicity. Since kidney is the critical target organ of chronic As toxicity, we carried out this study to investigate the effects of silibinin on As-induced toxicity in the kidney of rats. In experimental rats, oral administration of sodium arsenite [NaAsO₂, 5?mg/(kg?day)] for 4?weeks significantly induced renal damage which was evident from the increased levels of serum urea, uric acid, creatinine with a significant (p?<?0.05) decrease in creatinine clearance. As also significantly decreased the levels of urea, uric acid and creatinine in urine. A markedly increased levels of lipid peroxidation markers (thiobarbituric acid reactive substances and lipid hydroperoxides) and protein carbonyl contents with significant (p?<?0.05) decrease in non-enzymatic antioxidants (total sulfhydryl groups, reduced glutathione, vitamin C and vitamin E) and enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferase), Glutathione metabolizing enzymes (glutathione reductase and glutathione-6-phosphate dehydrogenase) and membrane bound ATPases were also observed in As treated rats. Co-administration of silibinin (75?mg/kg?day) along with As resulted in a reversal of As-induced biochemical changes in kidney accompanied by a significant decrease in lipid peroxidation and an increase in the level of renal antioxidant defense system. The histopathological and immunohistochemical studies in the kidney of rats also shows that silibinin (75?mg/kg?day) markedly reduced the toxicity of As and preserved the normal histological architecture of the renal tissue, inhibited the caspase-3 mediated tubular cell apoptosis and decreased the NADPH oxidase, iNOS and NF-κB over expression by As and upregulated the Nrf2 expression in the renal tissue. The present study suggests that the nephroprotective potential of silibinin in As toxicity might be due to its antioxidant and metal chelating properties, which could be useful for achieving optimum effects in As-induced renal damage.     

Doxorubicin-induced alterations in kidney functioning,oxidative stress,DNA damage,and renal tissue morphology; Improvement by Acacia hydaspica tannin-rich ethyl acetate fraction

Doxorubicin (DOX) is an anthracycline drug used for cancer treatment. However, its treatment is contiguous with toxic effects. We examined the nephroprotective potential of A. hydaspica polyphenol-rich ethyl acetate extract (AHE) against DOX persuaded nephrotoxicity. 36 male Sprague Dawley rats were randomly assorted into 6 groups. Control group received saline; DOX group: 3 mg/kg b.w. dosage of DOX intraperitoneally for 6 weeks (single dose/week). In co-treatment groups, 200 and 400 mg/kg b.w AHE was given orally for 6 weeks in concomitant with DOX (3 mg/kg b.w, i.p. injection per week) respectively. Standard group received silymarin 400 mg/kg b.w daily + DOX (single dose/week). Biochemical kidney function tests, oxidative stress markers, genotoxicity, antioxidant enzyme status, and histopathological changes were examined. DOX caused significant body weight loss and decrease kidney weight. DOX-induced marked deterioration in renal function indicators in both urine and serum, i.e., PH, specific gravity, total protein, albumin, urea, creatinine, uric acid, globulin, blood urea nitrogen, etc. Also, DOX treatment increases renal tissue oxidative stress markers, while lower antioxidant enzymes in tissue along with degenerative alterations in the renal tissue compared to control rats. AHE co-treatment ameliorates DOX-prompted changes in serum and urine chemistry. Likewise, AHE treatment decreases sensitive markers of oxidative stress and prevented DNA damages by enhancing antioxidant enzyme levels. DOX induction in rats also caused DNA fragmentation which was restored by AHE co-treatment. Moreover, the histological observations evidenced that AHE effectively rescued the kidney tissue from DOX interceded oxidative damage. Our results suggest that co-treatment of AHE markedly improve DOX-induced deleterious effects in a dose-dependent manner. The potency of AHE co-treatment at 400 mg/kg dose is similar to silymarin. These outcomes revealed that A. hydaspica AHE extract might serve as a potential adjuvant that avoids DOX-induced nephrotoxicity.     

Anti-oxidative effect of a protein from Cajanus indicus L against acetaminophen-induced hepato-nephro toxicity

Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.     

Clemizole hydrochloride,a potent TRPC5 calcium channel inhibitor,prevents cisplatin-induced nephrotoxicity in Spraque–Dawley rats

Cis-diamminedichloroplatinum (II) (cisplatin, Cis) is widely employed to treat several types of cancer. It has many important toxic side effects; one of the most important of which is nephrotoxicity. Clemizole hydrochloride (Clem) as the most potent inhibitor of TRPC5 channels was tested in an animal model of Cis-induced nephrotoxicity. Rats were divided into the following groups: control; Cis (8 mg/kg); Cis + 1 mg/kg Clem; Cis + 5 mg/kg Clem; Cis + 10 mg/kg Clem. Kidney injury was detected by histopathological and biochemical analysis. Urine urea nitrogen (UUN), creatinine, urine neutrophil gelatinase-associated lipocalin (NGAL), serum catalase (CAT), and malondialdehyde (MDA) levels were determined by enzyme-linked immunosorbent assay. Total antioxidant status (TAS) and total oxidant status (TOS) were studied using a colorimetric assay. Nephrin, synaptopodin, and Rac family small GTPase 1 (RAC1) expressions were detected by Western blot analysis. Cis was found to induce histopathological alterations, including tubular degeneration, congestion, hemorrhage, hyaline casts, glomerular collapse, and apoptotic cell death. Clem at a dose of 1 and 5 mg/kg attenuated histopathological alterations. UUN, creatinine, and NGAL levels increased in the Cis-administered group, while all doses of Clem decreased in those. CAT and TAS levels decreased, while TOS and oxidative stress index levels increased in the Cis-treated group. A dose of 1 and 5 mg Clem showed antioxidant effects against oxidative stress. Cis induced lipid peroxidation by increasing MDA levels. All doses of Clem reduced MDA levels. Nephrin and synaptopodin expressions were decreased by Cis, and all doses of Clem increased that. All doses of Clem successfully depressed RAC1 expression. Clem showed a highly ameliorating effect on toxicity caused by Cis by blocking TRPC5 calcium channels.     

Attenuation of oxidative stress, inflammation and early markers of tumor promotion by caffeic acid in Fe-NTA exposed kidneys of Wistar rats

Iron nitrilotriacetate (Fe-NTA), a chief environmental pollutant, is known for its extensive toxic manifestations on renal system. In the present study, caffeic acid, one of the most frequently occurring phenolic acids in fruits, grains, and dietary supplements was evaluated for its shielding effect against the Fe-NTA-induced oxidative, inflammatory, and pathological damage in kidney. Fe-NTA was administered (9 mg Fe/kg body weight) intraperitoneally to the Wistar male rats on 20th day while caffeic acid was administered orally (20 and 40 mg/kg body weight) before administration of Fe-NTA. The intraperitoneal administration of Fe-NTA-enhanced lipid peroxidation, xanthine oxidase, and hydrogen peroxide generation with reduction in renal glutathione content, antioxidant enzymes, viz., catalase, glutathione peroxidase, and glutathione reductase. A sharp elevation in the levels of myloperoxidase, blood urea nitrogen (BUN), and serum creatinine has also been observed. Tumor promotion markers viz., ornithine decarboxylase (ODC) and [(3)H] thymidine incorporation into renal DNA were also significantly increased. Treatment of rats orally with caffeic acid (20 and 40 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P < 0.001), lipid peroxidation (P < 0.001), γ-glutamyl transpeptidase (P < 0.01), and H(2)O(2) (P < 0.01). There was significant recovery of renal glutathione content (P < 0.001) and antioxidant enzymes (P < 0.001). There was also a reversal in the enhancement of renal ODC activity, DNA synthesis, BUN, and serum creatinine (P < 0.001). All these changes were supported by histological observations. The results indicate that caffeic acid may be beneficial in ameliorating the Fe-NTA-induced oxidative damage and tumor promotion in the kidney of rats.     

Modulation of cyclophosphamide-induced early lung injury by curcumin,an anti-inflammatory antioxidant

Cyclophosphamide causes lung injury in rats through its ability to generate free radicals with subsequent endothelial and epithelial cell damage. In order to observe the protective effects of a potent anti-inflammatory antioxidant, curcumin (diferuloyl methane) on cyclophosphamide-induced early lung injury, healthy pathogen free male Wistar rats were exposed to 20 mg/100 g body weight of cyclophosphamide, intraperitoneally as a single injection. Prior to cyclophosphamide intoxication oral administration of curcumin was performed daily for 7 days. At various time intervals (2, 3, 5 and 7 days post insult) serum and lung samples were analyzed for angiotensin converting enzyme, lipid peroxidation, reduced glutathione and ascorbic acid. Bronchoalveolar lavage fluid was analyzed for biochemical constituents. The lavage cells were examined for lipid peroxidation and glutathione content. Excised lungs were analyzed for antioxidant enzyme levels. Biochemical analyses revealed time course increases in lavage fluid total protein, albumin, angiotensin converting enzyme (ACE), lactate dehydrogenase, N-acetyl--D-glucosaminidase, alkaline phosphatase, acid phosphatase, lipid peroxide levels and decreased levels of glutathione (GSH) and ascorbic acid 2, 3, 5 and 7 days after cyclophosphamide intoxication. Increased levels of lipid peroxidation and decreased levels of glutathione and ascorbic acid were seen in serum, lung tissue and lavage cells of cyclophosphamide groups. Serum angiotensin converting enzyme activity increased which coincided with the decrease in lung tissue levels. Activities of antioxidant enzymes were reduced with time in the lungs of cyclophosphamide groups. However, a significant reduction in lavage fluid biochemical constituents, lipid peroxidation products in serum, lung and lavage cells with concomitant increase in antioxidant defense mechanisms occurred in curcumin fed cyclophosphamide rats. Therefore, our results suggest that curcumin is effective in moderating the cyclophosphamide induced early lung injury and the oxidant-antioxidant imbalance was partly abolished by restoring the glutathione (GSH) with decreased levels of lipid peroxidation.     

Naringenin ameliorates Cyclophosphamide-induced nephrotoxicity in experimental model

Cyclophosphamide (CP) is widely described in the management of several nonneoplastic and neoplastic disorders. Renal damage is the most reported toxic effect of CP in clinical practice.Our study aimed to evaluate the effect of Naringenin (NG) in attenuating renal damage induced by CP in an experimental model.A total of 32 rats were divided into four groups (n = 8): negative control: rats fed on a basal diet, positive control: rats injected intraperitoneally with CP 50 mg/kg of body weight/day, NG 100: rats treated with NG 100 mg/kg/day body orally with concomitant administration of CP as described before, and NG 200: rats treated with NG 200 mg/kg/day body orally daily + CP. At the end of the experimental protocol (21 days), blood creatinine and urea levels were measured. The antioxidant activities and lipid peroxidation products were measured in the renal tissues as indicators of oxidative damage. Histopathological examination and immunohistochemistry staining were also performed on renal tissues.Coadministration of NG along with CP significantly (p < 0.001) improved the renal function and antioxidant capacities compared with positive control animals. Furthermore, histopathological, and immunological examination of renal tissue confirmed the protective effect of NG against CP-induced nephrotoxicity.The current study showed that NG has the potential to protect CP-induced renal damage, which may be beneficial for further studies and the design of NG analogs to be useful in clinical practice against CP-induced nephrotoxicity.     

Topiramate and Vitamin E Modulate the Electroencephalographic Records,Brain Microsomal and Blood Antioxidant Redox System in Pentylentetrazol-Induced Seizure of Rats

We investigated the effects of vitamin E and topiramate (TPM) administrations on pentylentetrazol (PTZ)–induced blood and brain toxicity in rats. Forty rats were randomly divided into five equal groups. The first and second groups were used for the control and PTZ groups, respectively. Fifty or 100 mg TPM were administered to rats constituting the third and fourth groups for 7 days, respectively. The TPM and vitamin E combination was given to animals in the fifth group. At the end of 7 days, all groups except the first received a single dose of PTZ. Blood and brain samples were taken at 3 hrs after PTZ administration. Lipid peroxidation levels of plasma, erythrocyte, brain cortex and brain microsomal fraction; nitric oxide levels of serum; and the number of spikes and epileptiform discharges of the EEG were increased by PTZ administration. Plasma and brain vitamin E concentration, erythrocyte glutathione peroxidase (GSH-Px) activity and latency to first spike of the EEG were decreased by PTZ. Plasma lipid peroxidation levels in the third group and plasma and erythrocyte lipid peroxidation levels in the fifth group were decreased compared to the second group, whereas brain vitamin C, vitamin E, erythrocyte GSH-Px and reduced glutathione (GSH) values increased in the fifth group. Brain microsomal GSH levels and EEG records in the third, fourth and fifth groups were restored by the TPM and vitamin E treatment. In conclusion, TPM and vitamin E seems to have protective effects on PTZ-induced blood and brain toxicity by inhibiting free radicals and supporting the antioxidant redox system.     

Cytoprotective and antioxidant role of diallyl tetrasulfide on cadmium induced renal injury: an in vivo and in vitro study

Cadmium (Cd) is an environmental and industrial pollutant that affects various organs in humans and animals. A body of evidence has accumulated implicating the free radical generation with subsequent oxidative stress in the biochemical and molecular mechanisms of Cd toxicity. Since kidney is the critical target of Cd toxicity, we carried out this study to investigate the effects of diallyl tetrasulfide (DTS), an organosulfur compound derived from garlic on Cd induced toxicity in the kidney of rats and also in the kidney cell line (vero cells). In experimental rats, subcutaneous administration of Cd (3 mg/kg bw/day) for 3 weeks induced renal damage, which was evident from significantly increased levels of serum urea and creatinine with significant decrease in creatinine clearance. A markedly increased levels of lipid peroxidation markers (thiobarbituric acid reactive substances and lipid hydroperoxides) and protein carbonyl contents with significant decrease in nonenzymic antioxidants (total sulphydryl groups, reduced glutathione, vitamin C and vitamin E) and enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase) as well as glutathione metabolizing enzymes (glutathione reductase, and glucose-6-phosphate dehydrogenase) were also observed in Cd intoxicated rats. Coadministration of DTS (40 mg/kg bw/day) and Cd resulted in the reversal of the kidney function accompanied by a significant decrease in lipid peroxidation and increase in the antioxidant defense system. In vitro studies with vero cells showed that incubation of DTS (5-50 microg/ml) with Cd (10 microM) significantly reduced the cell death induced by Cd. DTS at 40 microg/ml effectively blocked the cell death and lipid peroxidation induced by Cd (10 microM) indicating its cytoprotective property. Further, the flow cytometric assessment on the level of intracellular reactive oxygen species using a fluorescent probe 2', 7'-dichlorofluorescein diacetate (DCF-DA) confirmed the Cd induced intracellular oxidative stress in vero cells, which was significantly suppressed by DTS (40 microg/ml). The histopathological studies in the kidney of rats also showed that DTS (40 mg/kg bw/day) markedly reduced the toxicity of Cd and preserved the architecture of renal tissue. The present study suggests that the cytoprotective potential of DTS in Cd toxicity might be due to its antioxidant and metal chelating properties, which could be useful for achieving optimum effects in Cd induced renal damage.