Lipid Peroxidation In Renal Tissue Research Articles

Protective efficacy of Tephrosia purpurea against Aflatoxin B1 induced oxidative damage in rats

Tephrosia purpurea (TP), commonly known as wild indigo, has a unique quality of healing all kinds of wounds and it is also an important ingredient of many Ayurvedic formulations. Thus, the present investigation was designed to validate and evaluate protective efficacy of ethanolic extract of Tephrosia purpurea (TP) against Aflatoxin B1 (AFB1) induced renal dysfunction. The ethanolic extract of Tephrosia purpurea was prepared by Soxhlet extraction method. For present study female rats (Wistar strain) were randomly divided into 6 groups with 6 animals in each group. The entire regime was of 28 days. AFB1 was administered at 200 µg/kg dose and TP was administered at three different doses (100, 200 and 300 mg/kg). 24 hours after last treatment the animals were euthanised various biochemical test were performed. AFB1 exposure significantly elevated uric acid, urea, creatinine in serum and lipid peroxidation in renal tissue indicating cellular damage. On the other hand, decline in activities of superoxide dismutase, catalase and reduced glutathione suggests exhaustion of endogenous defence system. Treatment with TP extract offers protection at all the three doses (100, 200 and 300 mg/kg). Although, maximum recovery was seen with 300 mg/kg dose of TP.

Rosiglitazone Suppresses Calcium Oxalate Crystal Binding and Oxalate-Induced Oxidative Stress in Renal Epithelial Cells by Promoting PPAR-γ Activation and Subsequent Regulation of TGF-β1 and HGF Expression.

Peroxisome proliferator-activated receptor- (PPAR-) γ is a ligand-dependent transcription factor, and it has become evident that PPAR-γ agonists have renoprotective effects, but their influence and mechanism during the development of calcium oxalate (CaOx) nephrolithiasis remain unknown. Rosiglitazone (RSG) was used as a representative PPAR-γ agonist in our experiments. The expression of transforming growth factor-β1 (TGF-β1), hepatocyte growth factor (HGF), c-Met, p-Met, PPAR-γ, p-PPAR-γ (Ser112), Smad2, Smad3, pSmad2/3, and Smad7 was examined in oxalate-treated Madin-Darby canine kidney (MDCK) cells and a stone-forming rat model. A CCK-8 assay was used to evaluate the effects of RSG on cell viability. In addition, intracellular reactive oxygen species (ROS) levels were monitored, and lipid peroxidation in renal tissue was detected according to superoxide dismutase and malondialdehyde levels. Moreover, the location and extent of CaOx crystal deposition were evaluated by Pizzolato staining. Our results showed that, both in vitro and in vivo, oxalate impaired PPAR-γ expression and phosphorylation, and then accumulative ROS production was observed, accompanied by enhanced TGF-β1 and reduced HGF. These phenomena could be reversed by the addition of RSG. RSG also promoted cell viability and proliferation and decreased oxidative stress damage and CaOx crystal deposition. However, these protective effects of RSG were abrogated by the PPAR-γ-specific inhibitor GW9662. Our results revealed that the reduction of PPAR-γ activity played a critical role in oxalate-induced ROS damage and CaOx stone formation. RSG can regulate TGF-β1 and HGF/c-Met through PPAR-γ to exert antioxidant effects against hyperoxaluria and alleviate crystal deposition. Therefore, PPAR-γ agonists may be expected to be a novel therapy for nephrolithiasis, and this effect is related to PPAR-γ-dependent suppression of oxidative stress.

Antioxidant Activity of Glycyrrhiza glabra L. Extract and Protective Effect of its Leaf Extract on Ethanol-Induced Nephrotoxicity in Male Rats

Introduction: Acute alcohol consumption leads to induction of lipid peroxidation in renal tissues, but its chronic consumption has moderate effects on biochemical and histological characteristics of this organ. Antioxidants have protective effects against ethanol-induced oxidative stress and tissue injury. The aim of this study was to assess antioxidant activity of Glycyrrhiza glabra leaf and stem extracts and the protective effect of its leaf extract on ethanol-induced nephrotoxicity. Materials & methods: Total phenol and flavonoid contents of leaf and stem extracts of G. glabra were measured by Folin Ciocalteu and AlCl3 assays, respectively. Antioxidant activity of both extracts was assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. In addition, protective effect of the leaf extract was assessed using biochemical and histological analyses of renal tissues of male Wistar rats, which were divided into four groups including group 1 or control (received 1 ml distilled water daily), group 2 or ethanol group (received 1 ml of 50% ethanol daily), group 3 or ethanol + leaf extract group (received 1 ml of 50% ethanol + 500 mg/kg leaf extract daily), and group 4 (received 500 mg/kg of leaf extract daily). All treatments are performed through intragastric administration. Biochemical and histological analyses were used for the evaluation of nephrotoxicity. For histological study, the samples were stained with Hematoxylin-Eosin and examined by light microscopy. Finally, all the data were analyzed by SPSS (Ver. 20) and grouped by Duncan's Multiple Range Test at P less-than 0.05 level. Findings: There was no significant difference between total phenol contents of the stem and leaf extracts. However, the stem extract showed a higher total flavonoid content than the leaf extract. Also, both the extracts showed higher antioxidant activities (86-93%) than that of ascorbic acid (71%). Results from biochemical analysis indicated a significant increase in superoxide dismutase (SOD) activity and H2O2 content in the renal tissues of ethanol-treated rats in comparison with other groups; however, there were no significant changes in total protein and malondialdehyde (MDA) contents. Results from histological examination showed that alcohol consumption intensity injured kidney tissues, which was effectively moderated by the studied extract. Discussion & Conclusions: Results from the present study showed that G. glabra extract has biological activity and can be used in future as a new natural antioxidant in food and drug industries.

Alteration in thiols homeostasis, protein and lipid peroxidation in renal tissue following subacute oral exposure of imidacloprid and arsenic in Wistar rats.

The aim of present study was to assess whether No Observed Effect Level (NOEL) of imidacloprid (IMI) potentiates the arsenic induced renal toxicity at its maximum contaminant level in drinking water in Wistar rats. Significant elevation of lipid and protein oxidation with reduced level of total thiols and antioxidant enzymes (catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase and glutathione-s-transferase) in renal tissue may have contributed to increased renal plasma biomarkers (creatinine and blood urea nitrogen) following repeated exposure of IMI and arsenic alone and in-combination. The altered renal biomarkers in co-exposed groups corroborated with histopathological alterations in renal tissue. The observations indicated that altered thiol homeostasis in renal tissue may be associated with increased lipid and protein oxidation in IMI and arsenic administered rats. It is concluded that administration of IMI potentiate the arsenic induced renal damage in Wistar rats.

Egyptian Propolis Alleviates Gentamicin-Induced Nephrotoxicity in Rats

The objective of this study was to evaluate the effectiveness of oral administration of ethanol extract of propolis against gentamicin induced nephrotoxicity in rats. Oral administration of ethanol extract of propolis (EEP) at doses 25, 50 and 100 mg/kg.b.wt. orally/daily for 7 days) against gentamicin- (GM) at dose 100 mg/kg b.wt., i.p./daily for 7days) induced nephrotoxicity in six equal groups of adult male Sprague-Dawley rats. Blood was collected 24 h after the last injection for determination of serum creatinine, urea, and aspartate aminotransferase (AST) activity. Rats were euthanized and kidney tissue specimens were collected for determination of oxidative/antioxidative biomarkers, gene expression for antioxidative enzymes and DNA fragmentation. Significant increase in serum creatinine, urea and AST activity at the same time, and a depletion of aspartate aminotransferase activity was recorded in renal homogenate of GM only–treated rats compared to control group. Lipid peroxidation in renal tissue showed significant elevation in GM-only treated group, however, superoxide dismutase, glutathione peroxidase and catalase and its gene expression were markedly decreased. DNA fragmentation was significantly increased in renal tissue of GM- only treated rats. Oral administration of EEP exhibited curative effects by reversing GM-induced alterations in serum biochemical and renal tissue oxidative stress biomarkers. In conclusion, propolis is effective in preventing or ameliorating oxidative stress of gentamicin.

Silymarin and milk thistle extract may prevent the progression of diabetic nephropathy in streptozotocin-induced diabetic rats

Objectives: To investigate the effect of silymarin and milk thistle extract on the progression of diabetic nephropathy (DN) in rats. Methods: Diabetes was induced with a single intraperitoneal (IP) injection of streptozotocin (STZ) (60 mg/kg). Silymarin (100 mg/kg/d) or the extract (1.2 g/kg/d) was gavaged for 4 weeks. Blood glucose (BS), serum urea (Su), serum creatinine (Scr), and 24-h urine protein (Up) were measured and glomerular filtration rate (GFR) was calculated. Concentration of thiobarbituric acid reactive species (TBARS) and activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were evaluated in the renal tissue. Results: Data were expressed as mean ± SEM. Silymarin or the extract had no significant effect on BS, Scr, and GFR. Both milk thistle extract and silymarin, respectively, decreased Su (mg/dL) (87.1 ± 7.78, p < 0.001; 84.5 ± 7.15, p < 0.001), Up (mg) (5.22 ± 1.56, p = 0.014; 5.67 ± 0.86, p = 0.034), and tissue TBARS (nmol/mg protein) (0.67 ± 0.04, p < 0.001; 0.63 ± 0.07, p < 0.001) in diabetic rats, compared to diabetic control (DC) (Su: 131.0 ± 4.55, Up: 8.3 ± 0.84, TBARS: 0.94 ± 0.06). Both the extract and silymarin could increase the activity of CAT (IU/mg protein) (25.5 ± 4.0, p = 0.005; 20 ± 1.8, p = 0.16) and GPx (IU/mg protein) (0.86 ± 0.05, p = 0.005; 0.74 ± 0.04, p = 0.10), respectively, in diabetic rats compared to DC (CAT = 14.4 ± 2.0, GPx = 0.57 ± 0.02). Conclusion: Milk thistle extract, to a lesser extent silymarin, can attenuate DN in rats possibly by increasing kidney CAT and GPx activity and decreasing lipid peroxidation in renal tissue.

MS387 FDG-PET/CT AND MRI EVALUATION OF THE EFFECT OF DALCETRAPIB ON ATHEROSCLEROTIC PLAQUE PROGRESSION/REGRESSION: DESIGN OF THE DAL-PLAQUE STUDY

Industrial and occupational exposure to chromium compounds, particularly hexavalent chromium (Cr(VI))-containing compounds are often known to cause acute renal injury (ARI) in humans and animals. Its nephrotoxicity is associated with an increased formation of reactive oxygen species and lipid peroxidation in renal tissue. Recent studies suggest that antioxidants of the vitamin E family have protective effects against metal toxicity. Tocotrienols are known to have greater antioxidant activity than tocopherols and protect more efficiently against some free radical-related diseases than does tocopherols. In the present study, ARI induced by potassium dichromate (K2Cr2O7) has been used as a model to investigate the possible nephroprotective effect of tocotrienol-rich fraction (TRF) from palm oil. Wistar male rats having an average body weight (bw) of 210 g were divided into four groups. The first group was taken as control and injected with vehicle alone while the second group was drug control and ingested with TRF (200 mg/kg, bw, orally, once daily for 21 days); the third group served as toxicant and was pre-treated with saline, followed by a single subcutaneous (SC) injection of K2Cr2O7 (15 mg/kg bw). The fourth group was pre-treated with TRF and subsequently injected with K2Cr2O7 (same dose as for the third group). Renal functions, oxidative and nitrosative stress were evaluated on days 0, 1, 2, 4, 7, 11 and 14 after treatment with K2Cr2O7. The results revealed altered proximal tubular function; decreased glomerular filtration accompanied by oxidative damage 48 h after exposure to dichromate; while in the TRF-treated group proximal reabsorptive function, glomerular function and the cellular redox status were sustained. These results were further supported and confirmed by histological findings. The study suggests that TRF is effective in preventing K2Cr2O7-induced acute renal injury, but more studies are needed to confirm the effects of TRF as a nephroprotective agent.

Nephroprotective action of tocotrienol-rich fraction (TRF) from palm oil against potassium dichromate (K 2Cr 2O 7)-induced acute renal injury in rats

Industrial and occupational exposure to chromium compounds, particularly hexavalent chromium (Cr(VI))-containing compounds are often known to cause acute renal injury (ARI) in humans and animals. Its nephrotoxicity is associated with an increased formation of reactive oxygen species and lipid peroxidation in renal tissue. Recent studies suggest that antioxidants of the vitamin E family have protective effects against metal toxicity. Tocotrienols are known to have greater antioxidant activity than tocopherols and protect more efficiently against some free radical-related diseases than does tocopherols. In the present study, ARI induced by potassium dichromate (K 2Cr 2O 7) has been used as a model to investigate the possible nephroprotective effect of tocotrienol-rich fraction (TRF) from palm oil. Wistar male rats having an average body weight (bw) of 210 g were divided into four groups. The first group was taken as control and injected with vehicle alone while the second group was drug control and ingested with TRF (200 mg/kg, bw, orally, once daily for 21 days); the third group served as toxicant and was pre-treated with saline, followed by a single subcutaneous (SC) injection of K 2Cr 2O 7 (15 mg/kg bw). The fourth group was pre-treated with TRF and subsequently injected with K 2Cr 2O 7 (same dose as for the third group). Renal functions, oxidative and nitrosative stress were evaluated on days 0, 1, 2, 4, 7, 11 and 14 after treatment with K 2Cr 2O 7. The results revealed altered proximal tubular function; decreased glomerular filtration accompanied by oxidative damage 48 h after exposure to dichromate; while in the TRF-treated group proximal reabsorptive function, glomerular function and the cellular redox status were sustained. These results were further supported and confirmed by histological findings. The study suggests that TRF is effective in preventing K 2Cr 2O 7-induced acute renal injury, but more studies are needed to confirm the effects of TRF as a nephroprotective agent.

Acetaminophen induced renal injury via oxidative stress and TNF-α production: Therapeutic potential of arjunolic acid

Acetaminophen (APAP) causes acute and chronic renal failure. The mechanisms leading to hepatic injury have been extensively studied, but the molecular mechanisms regarding APAP-induced nephro-toxicity are poorly defined. In earlier studies, we have demonstrated that arjunolic acid (AA) possesses protective roles against chemically induced organ pathophysiology. The purpose of the present study was to explore whether AA plays any protective role against APAP induced acute renal toxicity; and if so, what pathways it utilizes for the mechanism of its protective action. Exposure of rats with a nephro-toxic dose of APAP altered a number of biomarkers (like blood urea nitrogen and serum creatinine levels, etc.) related to renal oxidative stress, decreased antioxidant activity, elevated renal tumor necrosis factor-α and nitric oxide levels. AA treatment both pre- and post to APAP exposure protected the alteration of these biomarkers, compensated deficits in the antioxidant defense mechanisms, and suppressed lipid peroxidation in renal tissue. Investigating the inherent molecular signaling of this pathophysiology and its protection, we found that the mitochondrial pathway was not activated during APAP-induced cell death as no dissipation of mitochondrial membrane potential or release of cytochrome C was detected in the respective experiments. Our experimental evidence suggests that APAP-induced nephro-toxicity is a caspase-dependent process that involves activation of caspase-9 and caspase-3 in the absence of cytosolic cytochrome C release. These results provide evidence that inhibition of NO overproduction and maintenance of intracellular antioxidant status may play a pivotal role in the protective effects of AA against APAP-induced renal damage. AA represents a potential therapeutic option to protect renal tissue from the detrimental effects of acute acetaminophen overdose.

INFLUENCE OF ENALAPRIL, DIGOXIN, ATENOLOL AND DILTIAZEM ON LIPID PEROXIDATION IN EXPERIMENTAL MODEL OF COMPLEX METABOLIC DISORDERS

Aim. To study influence of enalapril, digoxin, atenolol and diltiazem on lipid peroxidation and antioxidative protection in experimental disorders of glucose and lipid metabolism. Material and methods. White nonlinear mice were used for modeling of the complex metabolic disorders by alloxan and cholesterol infusion. Evaluation of acute drug toxicity and indicators of lipid peroxidation and antioxidant protection was performed. Superoxide dismutase and catalase activity, malondialdehyde concentration were evaluated. Results. Toxicity of digoxin, diltiazem, atenolol in complex metabolic disorders was increased, and toxicity of enalapril was unchanged. Enalapril had antioxidant effect. Atenolol had prooxidative effect in myocardium and kidneys, and diltiazem - in kidneys. Conclusion. Enalapril showed antioxidant effect and decreased concentration of secondary products of lipid peroxidation in renal tissue. It may be considered as the first line drug in complex metabolic disorders.

Therapeutic potential of hemin in acetaminophen nephrotoxicity in rats

The therapeutic potential of hemin, the heme oxygenase-1 inducer, was investigated against renal damage induced by acute acetaminophen overdose in rats. Nephrotoxicity was induced by a single oral dose of acetaminophen (2.5 g/kg). Hemin was given as a single s.c. injection (40 μmol/kg), 1 h following acetaminophen administration. Hemin treatment restored blood urea nitrogen and serum creatinine levels that were elevated by acetaminophen. Hemin also compensated deficits in the antioxidant defense mechanisms (reduced glutathione, and catalase and superoxide dismutase activities), and suppressed lipid peroxidation in renal tissue resulted from acetaminophen administration. Hemin attenuated the acetaminophen-induced elevations in renal tumor necrosis factor-α and nitric oxide levels, and caspase-3 activity. Additionally, hemin ameliorated acetaminophen-induced renal damage observed by light microscopic examination. The therapeutic effect afforded by hemin was abolished by prior administration of zinc protoporphyrin-IX, the heme oxygenase-1 inhibitor. It was concluded that hemin represents a potential therapeutic option to protect renal tissue from the detrimental effects of acute acetaminophen overdose.

Methotrexate-induced renal oxidative stress in rats: the role of a novel antioxidant caffeic acid phenethyl ester

The exact mechanisms of methotrexate-induced renal toxicity have not yet been determined. However, several hypotheses have been put forward, including oxidative stress. The aim of this study was to investigate the role of caffeic acid phenethyl ester (Caffeic Ester), a novel antioxidant, on methotrexate-induced renal oxidative stress in rats. Nineteen adult male rats were equally divided into three experimental groups as follows: control group, methotrexate-treated group, and methotrexate+Caffeic Ester-treated group. A single dose of methotrexate (20 mg/kg) was administered intraperitoneally (ip). Caffeic Ester (10 micromol/kg) was administered ip, once daily for seven days. Malondialdehyde (MDA) levels (an index of lipid peroxidation) were used as a marker of oxidative stress-induced renal injury. Similarly, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined to evaluate the changes of antioxidant status in renal tissue. Methotrexate administration to control rats increased MDA levels (P<0.0001), but decreased SOD, CAT and GSH-Px activities in renal tissue (P<0.0001). Caffeic Ester+ methotrexate treatment caused a significant decrease in MDA levels (P<0.001), and caused an increase in SOD, CAT and GSH-Px activities when compared with methotrexate treatment alone (P<0.001, <0.05, <0.0001, respectively). In conclusion, methotrexate leads to a reduction in antioxidant enzymatic defense capacity and causes lipid peroxidation in renal tissue. Similarly, Caffeic Ester exhibits protective effects on methotrexate-induced renal oxidative impairment in rats.

Protective effect of erythropoietin on renal ischemia and reperfusion injury

Multiple protective effects of erythropoietin (EPO), such as antiapoptotic, antioxidant, angiogenic and neuroprotective effects, against ischemia have been demonstrated in cell culture and animal models. Genistein is also a potent tyrosine kinase inhibitor. The aims of the present study were to evaluate the effects of EPO on renal ischemia/reperfusion injury and to determine the role of the tyrosine kinase pathway on this process. Sprague-Dawley rats were assigned to five groups: (i) sham (Group I); (ii) control with renal ischemia (right nephrectomy and clamping on the left renal pedicle for 45 min and reperfusion; Group II); (iii) EPO + ischemia (Group III); (iv) genistein (an inhibitor of tyrosine kinase) + ischemia (Group IV); and (v) EPO + genistein + ischemia (Group V). Recombinant human EPO (1000 IU/kg) and genistein (10 mg/kg) were given 2 hours before ischemia. Blood samples and the left kidney were obtained after 45 min of reperfusion from half of the rats and after 24 h from the other half. The blood urea nitrogen, creatinine, tumour necrosis factor-alpha (P < 0.05) and interleukin-2 (P < 0.01) levels, and renal tissue lipid peroxidation (P < 0.05) were significantly lower in Group III than in Group II at 45 min of reperfusion. Following 24 h of reperfusion, EPO decreased tissue peroxidation and histopathological injury, whereas genistein reversed it. The most prominent ischemic injury was observed in Group IV in which genistein was administered. There was no significant difference between Groups II and V. These results suggest that EPO is effective in attenuating renal ischemia/reperfusion injury, and this effect may be related to tyrosine kinase activity.

Morphologic changes and lipid peroxidation in renal tissues of young rats following intestinal ischemia-reperfusion.

Intestinal ischemia-reperfusion (IIR) is a complex phenomenon causing local and remote tissue destruction, and even multiple-organ failure. To examine the hypothesis that IIR affects renal function, 21-day-old male Sprague-Dawley rats underwent 45 min superior mesenteric artery occlusion and control rats were subjected to a sham laparotomy. After 2 and 24 h and 1 week of reperfusion, blood was sampled for urea and the kidneys were harvested for lipid peroxidation and histologic examination. Malondialdehyde (MDA) levels as an indicator of lipid peroxidation were significantly increased in renal tissue after 2 h of reperfusion, and this finding was in accordance with serum urea levels (SU) and endothelial injury. However, at 24 h of reperfusion MDA and SU had returned to normal. These data were supported by electron-microscopic studies suggesting reversibility of the changes. It is concluded that IIR leads to renal injury and that free radicals may be responsible for this injury.

Lazaroids prevent acute cyclosporine-induced renal vasoconstriction.

Cyclosporine (CsA)-induced nephrotoxicity may be due to intrarenal vasoconstriction and glomerular hypoperfusion. Several factors, including endothelin and prostanoids, are suggested mediators of this response. Recent evidence suggests that CsA leads to increased oxygen-derived free radical (ODFR) production and lipid peroxidation in renal tissue. Whether this leads to alterations in renal vessel reactivity is unclear. Lazaroids, such as U74389G, are radical-quenching antioxidants that inhibit ODFR-induced lipid peroxidation and may improve renal function after ischemia and reperfusion. We hypothesized that ODFRs contribute to CsA-induced alterations of the renal microcirculation. Rat hydronephrotic kidneys were studied by video microscopy. Interlobular arteriolar diameter and flow, afferent and efferent arteriolar diameters, and cardiac output were measured at 15-min intervals for 120 min. U74389G or its vehicle was infused 15 min before topical application of CsA to the kidney. The results were compared with U74389G alone and normal saline. CsA administration caused renal microvascular vasoconstriction (10-25% below baseline) and hypoperfusion (35% below baseline). Both vasoconstriction and hypoperfusion were significantly attenuated by U74389G (5-8% and 20% below baseline, respectively). Inhibition of lipid peroxidation by U74389G maintained renal blood flow during acute CsA administration. These data suggest that ODFRs are involved in the renal microvascular response to CsA. Inhibition of ODFR-induced lipid peroxidation may help prevent CsA-induced glomerular hypoperfusion. Lazaroids may prove an effective adjunct in reducing CsA-induced nephrotoxicity.

Lipid peroxidation and antioxidant defense mechanisms in rat renal tissue after daunorubicin administration.

Redox cycling compounds such as daunorubicin have been assumed to be toxic because they stimulate reactive oxygen-mediated lipid peroxidation. Furthermore, both DT-diaphorase and glutathione (GSH) have been regarded as protective cellular compounds against daunorubicin cardiotoxicity, but their role in daunorubicin nephrotoxicity remains unclear. To investigate this issue, 10 adult Wistar rats were twice injected with a single dose of 20 mg/kg body weight daunorubicin into the tail vein; the interval between injections was 48 h. A control group of 10 rats were injected with normal saline. One day after the second injection, all the animals were sacrificed and their kidneys were analyzed for malondialdehyde (MDA) as an index of lipid peroxidation, DT-diaphorase activity, and GSH and glutathione disulphide (GSSG) content. A significant increase of MDA concentration (2.41 vs. 1.64 p < 0.001) and DT-diaphorase activity (0.2 vs. 0.12, p < 0.001) was found in the renal tissue of daunorubicin injected rats. In contrast, GSH and GSSG levels were decreased in those animals (566 vs. 1282, p < 0.001 and 115 vs 187, p < 0.01, respectively). The results of this study give evidence that a high dosage of daunorubicin induces lipid peroxidation in renal tissue of rats stimulating the activation of DT-diaphorase and the detoxificative depletion of GSH.

Stimulatory effect of cisplatin on production of lipid peroxidation in renal tissues.

Cisplatin (cis-diamminedichloroplatinum II), an anticancer chemotherapeutic agent with the dose-limiting side effect of nephrotoxicity, caused a statistically significant increase in lipid peroxidation, monitored by measuring the production of malondialdehyde, in rat kidney 72 hr after injection. Treatment of rats beforehand with the antioxidant alpha-tocopherol or N-N'-diphenyl-p-phenylenediamine (DPPD) effectively decreased such peroxidation. DPPD was a more effective inhibitor than alpha-tocopherol, since it is known for its ability to scavenge free radicals more powerfully. The ability of renal cortical slices to accumulate p-aminohippurate (PAH) was examined as a biochemical parameter that would change in nephrotoxicity. The ability to accumulate PAH by the incubated slices decreased 72 hr after administration of cisplatin. The pretreatment with DPPD prevented the decrease in PAH accumulation in the slices from rats treated with cisplatin. Structural changes of the renal proximal tubule caused by cisplatin, analyzed in a transmission electron microscope, were also prevented by the pretreatment with DPPD. The results suggest that cisplatin affects renal tissues in which free radicals generated by cisplatin may interact with membrane lipids to cause the production of lipid peroxidation, which affects both cellular structure and function.