Role of Mesenchymal Stem Cell Therapy in Cisplatin Induced Nephrotoxicity in Adult Albino Rats: Ultrastructural & Biochemical Study.

Objective: Mesenchymal stem cells (MSCs) have generated a great deal of excitement and promise as a potential source of cells for cell-based therapeutic strategies. These data provide the clue of using MSCs in the current work in correcting cisplatin-induced nephrotoxicity, the severest adverse effect of the well-known anticancer drug; cisplatin. Methods: MSCs of bone marrow origin of femora and tibiae of adult albino rats were separated, grown, propagated in culture then identified by both morphology and CD29 surface marker detection. MSCs were injected into the rats’’ tail veins one day after a single dose (5 mg/kg body weight) of intraperitoneal injection of cisplatin. Four weeks later kidney tissue was examined histopathologically and ultra-structurally. Renal functions s(urea, creatinine) as well as serum electrolytes levels (Na, K) were estimated Results: Cisplatin group demonstrated atrophied glomeruli, thickened glomerular basement membrane, dilated urinary space, loss of proximal convoluted tubules brush borders, loss of podocyte pedicels and collagen deposition. Tubular cells showed vacuolization and nuclear membrane degeneration. Serum levels of urea, creatinine, Na and K were significantly elevated. MSCs ameliorated cisplatin-induced nephrotoxicity to a great extent as evidenced histologically, ultra-structurally and biochemically. Conclusion: MSCs have a potential therapeutic effect against cisplatin induced nephrotoxicity.

Assessment of the protective role of green tea on doxorubicin induced hepatic and renal injuries in albino rats

The present study has been undertaken to investigate the ameliorative effect of green tea [GT] on doxorubicin [Doxo]-induced hepatotoxicity and nephrotoxicity in albino rats. The harmful effects of Doxo on some antioxidant enzymes, catalase [CAT], superoxide dismutase [SOD] and glutathione-S-transferase [GST] were studied. Reduced glutathione [GSH] and malondialdehyde [MDA] in liver and kidney homogenates were investigated. Quantitative and qualitative extents of DNA damage in the liver cells were also estimated using Cornet assay. Thirty two male adult albino rats [180-200 g] were divided into four groups [n=8] as follows; [1] Control group: was orally administered 1 ml/rat of 0.5% carboxymethyl cellulose [CMC] in distilled water, [2] Doxo group: after 10 days, Doxo was administered a single i.p. dose of 15 mg/kg body weight, [3] GT group: rats received 100 mg/kg body weight, p.o. of GT for 10 days and [4] Doxo and GT group: rats received 100 mg/kg body weight, p.o. of GT for 10 days prior to Doxo administration as a single i.p. dose of 15 mg/kg body weight. Doxorubicin-induced significant increase in serum levels of AST, ALT and gamma-glutamyl transpeptidase [GGT] for liver and urea and creatinine for kidney which were decreased by pretreatment with GT. Total serum protein and albumin levels were decreased after treatment with Doxo but this effect was attenuated by pretreatment with GT. Catalase, SOD, GST activities and GSH content of liver and kidney were significantly elevated by pretreatment with GT compared to Doxo-treated rats. Doxorubicin significantly increased in MDA levels. DNA damage measured as tail length, tail DNA% and tail moment were increased after treatment of Doxo while pretreatment with GT improved this effect. This study suggests that green tea has potential protective effect against doxorubicin-induced hepatoxicity and nephrotoxicity. So, it may be worthy to consider the usefulness of GT as adjuvant therapy in cancer management

N-acetylcysteine attenuates cyclosporine-induced nephrotoxicity in male albino rats

Cyclosporine A [Cs A] is used for the treatment of autoimmune and inflammatory disorders. However, Cs A-induced nephrotoxicity remains an important clinical problem, and oxidative stress has been implicated as a possible responsible mechanism. We assessed the protective ability of N-acetylcysteine [NAC], an antioxidant, against Cs A-induced nephrotoxicity. Thirty adult male albino rats were used to study the effect of cyclosporine [Cs A] and the action of N-acetylcysteine [NAC] on certain renal parameters; Blood Urea Nitrogen [BUN] and creatinine. Malondialdehyde [MDA] and catalase [CAT] levels were used as biomarker for testing the antioxidant potential of the drug. Endothelin-l[ET-l] levels were estimated in plasma. Animals were randomly assigned into three groups. Group I rats as control, group 2 were treated with Cs A and group 3 with Cs A plus NAC. Cs A administration for 21 days produced elevated levels of MDA and decreased in antioxidant enzyme CAT and deteriorated the renal function as assessed by increased serum Blood Urea Nitrogen [BUN] and creatinine. Plasma ET-l was also elevated as compared to control groups. Oral administration of NAC [140 mg/kg/day] significantly attenuated renal dysfunction, reduced elevated levels of MDA, increased the level of CAT and decreased level of ET- 1. These results indicate that NAC produces a protective mechanism against Cs A-induced nephrotoxicity in rats and suggest a role of Cs A for oxidative stress and the nephroprotective role of NAC against Cs A-induced nephrotoxicity in rats

Therapeutic efficacy of alpha lipoic acid in combination with succimer against lead-induced oxidative stress, hepatotoxicity and nephrotoxicity in rats

Lead toxicity is a worldwide health problem due to continuous exposure of the population to lead in the environment especially workers in industries. It affects many body organs especially the liver and kidneys. The aim of this study is to investigate and compare the therapeutic potential of alpha lipoic acid [ALA] when it is administrated alone and in combination with succimer or dimercaptosuccinic acid [DMSA] against lead induced oxidative stress, hepatotoxicity and nephrotoxicity. Seventy five healthy male albino rats were used divided into 5 equal groups. Group [1] the control group was administrated distilled water orally for 6 weeks. Group [II] rats were given lead acetate [0.2%] in drinking water for 5 weeks and distilled water only orally during the 6[th] week. Group [III, IV and V] rats were given lead acetate [0.2%] in drinking water for 5 weeks followed by DMSA in a dose of 20 mg/kg body weigh/day intraperitoneally [i.p.] alone, ALA in a dose of 25 mg/kg body weigh/day [i.p.] alone and both drugs in combination during the 6[th] week only respectively. Rats were sacrificed after six weeks. Blood lead level serum lipid peroxides [TBARS], serum total antioxidant [TAG] and serum nitric oxide [NO] levels were measured. Also Liver function tests [serum alkaline phosphatase, glutamic oxalacetic transaminase and glutamaic pyruvic transaminase] were measured. In addition, kidney function tests [serum urea, creatinine and uric acid] were done. Results showed an increase in the mean of blood lead level, increase serum TBARS levels, decrease serum TAG and NG levels and increase levels of liver and kidney function tests in lead treated group. Treatment with DMSA alone resulted in reduction of blood lead levels, improvement of serum NG level but not decrease serum TBARS level and moderate decrease in the elevated liver and kidney function test parameters. Rats treated with ALA alone showed no reduction in the elevated blood lead levels, but decreased serum TBARS and improved serum NO, TAG levels, liver and kidney function tests. Rats treated with DMSA and ALA concurrently showed decrease in blood lead levels, decrease serum TBARS, increase serum NO and TAG levels to near normal level and corrected liver and kidney function tests. In conclusion administration of ALA has beneficial effect as thiol-mediated antioxidant function when given to occupationally exposed workers to lead and during treatment of lead poisoning with DMSA as it increases its efficacy

Carnosine protects against gentamicin-induced nephrotoxicity in rats

Acute renal failure is a major complication of gentamicin, limiting use of this antibiotic in treatment of gram negative infections. Reactive oxygen species are hypothesized to be a major factor in the nephrotoxicity of gentamicin and measures controlling this oxidative damage are widely appreciated. This work was conducted to test the hypothesis that treatment with carnosine, a biological antioxidant, may prevent or ameliorate acute renal injury, using a rat model of gentamicin-induced nephrotoxicity. Male wistar albino rats were assigned to one of six treatment groups; group I [control] rats were given normal saline injections daily for 10 days; group II rats were given IM gentamicin injections, 100 mg/kg/day, for 6 days: group III, IV and V rats were given gentamicin, together with IP carnosine injections 50, 100 and 200 mg/kg/day, respectively, for 10 days starting 4 days before gentamicin injections; and group VI rats were given only carnosine 200 mg/kg/day, for 10 days. All rats were weighed before and after experimentation, and 24 hour urine volume were collected in metabolic cages. At end of study, blood samples were collected for measurement of BUN, creatinine level and creatinine clearance. Rats were then sacrificed and the kidneys were excised. The left kidneys were homogenized and used for biochemical determination of MDA, GPX and SOD, while the right kidneys were processed for histological examination and scoring of renal cortical pathology. Results showed that gentamicin produced evident nephrotoxic effects revealed by; increased kidney weight, increased urine volume, elevations of serum levels of BUN and creatinine and decreased creatinine clearance; together with increased MDA, reduced GPX and SOD in kidney tissues. Marked histological alterations were also evident in the renal cortex [acute tubular necrosis of grade 2-3]. Carnosine treatment leads to significant dose-related attenuation of nephrotoxic effects of gentamicin revealed by reduction of the elevated biochemical parameters, improved oxidative status in the kidney, and amelioration of the histological changes. It is concluded that carnosine treatment could ameliorate the severity of renal cortical necrosis induced by gentamicin and maintain a better renal function. Thus, carnosine may be a useful candidate in the combination therapy with gentamicin to limit free radical-mediated renal injury

Pharmacokinetics effects of some insecticides on white albino rats

The treatment of adults' female albino rats with Maximum Residue Limit [MRL] to tomato fruits of the three organophosphorus insecticides namely, primiphos-methyl, chloriphos-methyl and fenitrothion [1, 0.5 and 0.5 ppm] respectively on different periods [from 1. 6, 12, 24, 48, 96 hours and 7 days] to indicate and follow-up the effect of these insecticides on liver and kidney functions. A significant increasing activities of Aspartate Amino Transferase [AST] were found. No changes in Alanine Amino Transferase [ALT] and Alkaline phosphatase activities were observed in treated rats by the MRLs of the tested insecticides as compared with control. The data gathered showed that there were no significant changes in creatinine levels and urea concentrations of the treated rats at the different periods after dosing by the MRL of the tested insecticides. The data also clearly indicated an insignificant decrease in total protein levels, observed in rats treated by MRL of the tested insecticides after 1, 6, 12, 24, 48, 96 hrs and 7 days of treatment. Cholesterol level displayed slight or insignificant increasing in rats which were treated with the aforementioned insecticides. Generally treating rats by MRL of the prementioned insecticides resulted in a small [deleterious] effect on some biochemical parameters after 7 days of treatment. No effects have been detected at the first hours of the experiments

Effect of vitamin E an antioxidant and deferoxamine an Iron chelator on gentamicin induced nephrotoxicity in albino rats

Gentamicin [GM] is widely used as a bactericidal agent for the treatment of severe gram negative infections. However, its clinical use is partially limited due to its nephrotoxicity. The present study was designed to investigate a possible protective role of vitamin E and / or deferoxamine against GM nephrotoxicity. Nephrotoxicity was induced in rats by GM [80 mg/ kg/d, IP] for 8 days characterized by increased serum creatinine, blood urea and renal malondialdehyde [MDA], decreased serum albumin in addition to proximal tubular necrosis. Treatment of rats with iron [8 mg/kg/d, IM] for 8 days with GM significantly potentiated GM-induced increases in serum creatinine, blood urea and renal malondialdehyde, decreased serum albumin and exacerbated renal histological damage. Deferoxamine [100 mg/kg/d, IP] was given for 11 days significantly reduced GM-induced increases in serum creatinine, blood urea and renal malondialdehyde, and ameliorated proximal tubular damage. Similarly, pretreatment of rats with vitamin E [250 mg/kg/d, orally] for 11 days with GM given during the last 8 days of treatment, was effective in GM-induced nephrotoxicity. Combined use of deferoxamine and vitamin E was more effective in mitigating disturbances in the assessed parameters. The present work indicates that vitamin E [due to antioxidant activity] and deferoxamine [due to iron chelating and antioxidant activities] have potential protective effects against GM nephrotoxicity

role of calcium channel blockers against cyclosporine-induced hepatorenal toxicity

The present work investigated the changes induced by cyclosporine on the liver and kidney and clarified the possible protective role of calcium channel blockers. Cyclosporine caused distortion of the liver parenchyma as well as severe congestion in the central vein. Also there was loss of cellular demarcation with indistinct cell boundaries. By the electron microscope the hepatocytes in the affected areas revealed depleted cytoplasm, and mitochondria with partial loss of their cristae. The rough endoplasmic reticiulum showed slight dilatation and fragmentation. The calcium channel blocker [amlodipine] enhanced the preservation of the control pattern in most hepatocytes apart from few hepatocytes showing areas of depletion, irregular arrangement of endoplasmic reticiulum, few glycogen granules and smaller nuclei. Regarding the kidney, cyclosporine caused different modalities of degeneration in the capillary tuft of the renal corpuscles. Both the proximal and distal tubules showed widening of their lumen, distortion of their cellular pattern As for the cells of the proximal tubules, they showed disrupted brush border, loss of the basal striations with irregular nuclei. Some tubules also contained areas of exudation. Extravasation of red blood corpuscles was evident. The podocytes, by the electron microscope, had vacuolated cytoplasm and irregular nuclei. The mesangial cells had paler matrix than the control group. Peritubular fibrosis was observed. The cytoplasm of the cells of the proximal tubules contained large lysosomes and autophagic vacuoles

postulated protective role of lacidipine and verapamil against cyclosporin A-induced nephrotoxicity and its relation to P-glycoprotein expression in rat kidney

Cyclosporin-A [CsA] has markedly improved the results of transplantation and its use is extended to include autoimmune and primary renal diseases. However, the major limitation of its use is its nephrotoxicity. P-glycoprotein [P-gp] is a transmembrane efflux pump for hydrophobic, potentially toxic compounds, including CsA. CsA has been shown to increase P-gp expression in tubular and endothelial cells. Aim of Work: The aim of the present study was to elucidate the protective effect of the calcium channel blockers lacidipine and verapamil against CsA-induced nephrotoxicity and the relation of this protective effect to P-gp expression in rat kidney. This study included 7 groups, each containing 7 rats: oral saline group. intraperitoneal [IP] saline group, CsA [25 mg/kg/] group: rats received CsA IP for 14 days, lacidipine [1 mg/kg/d] group: rats received lacidipine orally for 17 days, concomitant lacidipine and CsA group: rats received lacidipine for 3 days and concomitant with CsA for another 14 days, yerapamil [0.1 mg/kg/d] group: rats received erapamil i.p for 17 days and concomitant verapamil and CsA group: rats received verapamil for 3 days and concomitant with CsA for another 14 days Serum creatinine, histopathological and immunostaining for P-gp for rat kidneys were done for all rats. This study revealed that CsA significantly raised serum creatinine, produced vacuolization and necrosis in tubular cells and increased P-gp expression. Kidneys treated with lacidipine alone revealed no significant changes biochemically and histologically. When lacidipine was given with CsA, it significantly protected the kidneys against CsA-induced nephrotoxicity and increased expression of P-gp in kidneys. Verapamil alone caused mild nephrotoxicity in the form of vacuolization and increased serum creatinine level. It also inhibited P-gp expression in rat kidneys. Verapamil given with CsA significantly ameliorated CsA nephrotoxicity and decreased P-gp expression. lacidipine had protective effect against CsA nephrotoxicity more than verapamil. Hemodynamic effect is the main effect and moreover, lacidipine may protect via P-gp over- expression

Protective effect of polyaspartic acid on apoptosis induced aminoglycoside nephrotoxicity in rats. an immunohistochemical study of cell regulatory proteins [p53 and proliferating cell nuclear antigen]

Aminoglycoside antibiotics as gentamicin can produce irreversible, cumulative nepbrotoxicity due to the toxic injury of the renal tubular epithelial cells resulting in acute or chronic renal failure due to the prolonged exposure to small amounts [Lieberthal and Levine, 1996]. The aim of the present study was to evaluate the possible protective effect of polyaspartic acid on apoptosis-induced gentamicin toxicity in albino rats. For this purpose 70 male albino rats were equally divided into seven groups: control group, gentamicin groups [rats treated with geritamicin alone at daily doses of 10, 20 or 40mg/kg of body weight intraperitoneally] and protected groups [rats treated with polyaspartic acid [250 mg/kg/day subcutaneously] concurrently with gentamicin at the different studied doses. All rats were treated for seven consecutive days. Kidney cortex apoptosis was detected by the p53 antibodies. The cortical proliferative activity was determined by the proliferating cell nuclear antigen [PCNA] labeling index. The expression of p53 oncogene and the PCNA monoclonal antibodies were detected and quantitated using immunohistoehemical methods. The mean percentage of p53 positive cells in gentamicin treated rats at doses of 10, 20 and 40 mg/kg/day for seven days was 41.3 +/- 2.21,47 +/- 2.26 and 53.5 +/- 2.42 respectively, while that of PCNA positive cells was 21.5 +/- 1.96, 27.7 +/- 2.31 and 35.7 +/- 3.97 respectively. The apoptotic figures as well as the cell proliferative activity were used for assessing the efficacy of polyaspartic acid [PAA]. The mean percentage of p53 positive cells in protected rats at doses of 10, 20 and 40mg/kg/day for seven days was 22.4 +/- 2.07, 24.7 +/- 2.41 and 28.7 +/- 3.27 respectively, while that of PCNA positive cells was 2.8 +/- 0.98, 5.05 +/- 0.90 and 6.65 +/- 0.94 respectively. Rats treated with gentamicin alone developed an apoptotic process as part of the various cortical alterations induced by this antibiotic. Also a relation between gentamicin-induced tubular apoptosis and cortical proliferative response has been established. The marked apoptotic reaction induced by gentamicin in proximal tubules was dose dependent. In low doses it occurred in the absence of necrosis and it was correlated with the proliferative response. Coadministration of polyaspartic acid [PAA] with gentamicin proved to reduce significantly gentamicin-induced apoptosis. Although the underlying mechanism for this reduction remains uncertain, yet the molecular mechanism of the protective effect of PAA is most likely related to its biochemical mechanisms, which include antioxidative activities

Decalin-induced nephrotoxicity consequent to ovariectomy in female Rat

The aim of the present work was to test the influence of ovariectomy on the development of decalin kidney damage in female rats. A total of 60 female rats was used in this study and divided into three equal groups. Ovariectomy was done only to one group, treatment of an oral administration of decalin over a period of 12 days was given to this group and the other group, while the last group served as a control. Light and electron microscopic consequences of this treatment were examined by the end of the experiment. The results exhibited a destruction of the renal proximal convoluted tubules epithelium, which was mainly in the form of hyaline degeneration. It was suggested that the female rat kidney, which has been claimed not to suffer from exposure to decalin, was vulnerable to the damaging effect of decalin after ovariectomy. The reason for this change may be that the ovarian hormones can offer a protection against the toxic effect of decalin

comparative study of the possible protective role of vitamin E versus selenium on sodium arsenate induced nephropathy in male albino rats, histologicul and histochemical study

Drinking water contaminated by arsenic remains a major health problem. Selenium as a trace element and vitamin E have antioxidant properties and might be considered as protective elements. Forty-nine male albino rats were used in the present study to compare between the possible protective role of vitamin E versus selenium on sodium arsenate induced nephropathy. The animals were divided into 2 major groups, a control and an experimental group. Animals of the experimental group received sodium arsenate daily in a dose of 1 mg / kg / day. The experiment was conducted daily for 28 days. Animals were sacrificed; blood samples were obtained to measure the level of urea and creatinine. Kidney specimens were dissected, processed and examined histologically and histochemically. In animals of subgroup IIa which received sodium arsenate some glomeruli were seen to be congested, others showed atrophy of the glomerular tuft of capillaries. The cytoplasm of some of the cells lining the tubules showed vacuolations with ill-defined nuclei. Some renal tubules were seen to be dilated. Areas of congestion were demonstrated between the tubules in the cortex and medulla. There was highly significant increase in the mean value of the percentage of tubular damage. PAS stained sections showed localized thickening of the glomerular basement membrane, basement membrane of Bowman's capsule and that of the tubules. Mallory stained sections showed increased collagen fibers around the glomerular capillaries and in the interstitial tissue of the kidney. Decreased succinic dehydrogenase enzyme activity was observed in the cytoplasm of the renal tubules. Also there was reduction of alkaline phosphatase enzyme activity at the brush border of the PCTs. Urea and creatinine were highly significantly increased. In subgroup IIb animals which received sodium arsenate together with vitamin E, many of the nephrons showed similar picture to that of subgroup IIa which received sodium arsenate alone. While subgroup IIc animals which received sodium arsenate together with selenium showed similar histological, histochemical and biochemical results as those of the control. It is concluded that selenium showed more protective effect than vitamin E on arsenic induced nephropathy

Carnosine protection against cadmium-induced nephrotoxicity in male albino rats: a biochemical and histological study

Cadmium in a dose of 3 mg/kg body weight was administered subcutaneously for a total period of 14 weeks in male albino rats. This resulted in a significant decrease in rats' terminal body weights; but renal function tests, including serum levels of urea, creatinine and uric acid, showed a marked significant increase. Furthermore, both blood cadmium and kidney cadmium concentrations showed a significant increase in cadmium-treated animals. Carnosine when supplemented orally in a dose of 0.15 mg/kg body weight concurrently with cadmium administration showed an improvement in both body weight gain and renal biochemical function as well as morphological architecture, but still below the initial control values. In contrast, body weights as well as renal function and morphology were corrected and became near the control values. In contrast, body weights as well as renal function and morphology were corrected and become near the control values on increasing the dose of carnosine to 0.3 mg/kg. Furthermore, the level of cadmium in either blood or kidney tissue of animals received cadmium simultaneously with carnosine was also significantly lower than in those animals received cadmium alone

Early detection of radio contrast media induced nephropathy

Radio contrast media [RCM] induced nephropathy has been defined as an acute impairment of renal function following exposure to radiographic contrast materials after excluding other causes of renal impairment [Bersketh and Kjellstrand, 1984]. The aim of the present work is early detection of asymptomatic radio-contrast media associated nephrnpathy and its possible effect on glomerular-and tubular functions. The study included 35 subjects divided into two groups: Group I: 20 patients received RCM urographin l ml/kg body weight and Group II: 15 healthy persons as normal control who received normal saline as a placebo. Both groups were subjected to thorough clinical examination and the following laboratory investigations: urinary microalbuminuria before as well as 24 hours after RCM to test glomerular function urinary alkaline phosphatase before RCM administration as well as 5 hours. 24 hours as well as 5 days after as a test for tubular function. The results of the present study showed significant increase in microalbuminuria in group I patients after administration of RCM, also there was statistically significant increase in the mean values of urinary alkaline phosphatase observed 5 hours. 24 hours, and 5 days after RCM

Inhibition of gentamicin-induced nephrotoxicity by ascorbic acid and pyridoxal hydrochloride

This study was undertaken to compare the capability of blockade of gentamicin nephrotoxicity by either ascorbic acid [vitamin C] or pyridoxal hydrochloride [vitamin B6] and to evaluate whether their combination has a better protective effect than either alone, as manifested by changes in the serum urea and creatinine levels as well as the histological renal changes. For this purpose, 70 male Wister albino rats were equally divided into 7 groups. A negative control group receiving distilled water, a positive control group receiving vitamin C alone, a positive control group receiving vitamin B6, rats receiving gentamicin alone, rats receiving gentalicin as well as vitamin C, rats receiving gentamicin in addition to vitamin B6, and finally rats receiving gentamicin, vitamin C and vitamin B6. Our results showed that, vitamin B6 plays a better role in the protection against gentamicin nephrotoxicity than vitamin C, moreover, the combination of these two vitamins produced a better protection than either vitamin alone. Strict adherence to the prescribed dose of the aminoglycoside preparations especially gentamicin is required. In addition, a combination of vitamin C and vitamin B6 could provide adequate protection against gentamicin-induced nephrotoxitiy

use of "vinorelbine" in the Treatment of advanced non-small Cell lung cancer

This study included 19 patients suffering from advanced non-small cell lung cancer [NSCLC]. They were treated either with Vinorelbine-Cisplatinum; or Vinorelbine as a single agent for elderly patients, or those with poor performance status, or with renal impairment [9 cases]. Objective partial response was achieved in 5 cases [26%] with median duration of response for 25 weeks for the whole study group. The response was comparable in both treatment arms; with better tolerance in patients receiving Vinorelbine alone. This study demonstrates the efficiency of Vinorelbine in the treatment of advanced NSCLC either in combination with Cisplatinum, or as a single agent in elderly frail patients

Sensitive indicators of renal dysfunction among workers exposed to cadmium

Cadmium-induced renal tubular dysfunction was examined in 28 male workers in 2 electroplating factories. Forty comparable apparently healthy administrators constituted the control group. Both groups were submitted to a battery of serum and urinary nephrotoxicity markers to assess the renal effects. The study revealed that chronic exposure to cadmium was associated with renal function impairment evidenced by increased frequencies of abnormal values of most of the nephrotoxicity markers used. Urinary NAG correlated well with all exposure indices, on the other hand urinary B[2] micrglobulin [B[2]M] showed a significant positive correlation only with blood cadmium level which was weaker than that of urinary NAG. Urinary NAG detected a larger proportion of abnormalities among the exposed workers than B[2]M. NAG was suggested to be a sensitive and useful marker for biological monitoring of workers exposed to cadmium

Evaluation of gentamicin - induced nephrotoxicity in rats treated with low doses of ibuprofen and diclofenac sodium

The purpose of the present investigation was to examine the effects of two nonsteroidal anti-inflammatory drugs [NSAIDs], ibuprofen [20 mg/kg/day] and diclofenac sodium [2.5 mg/kg/day], on the severity of gentamicin - induced nephrotoxicity in rats. Administration of gentamicin [100 mg/kg/day] for 5 days resulted in a significant elevation in renal cortical total phospholipids accompanied by a significant decrease in cortical Na[ +/- ] K[ +/- ] adenosine triphosphatase [ATPase] activity [P<0.01]. These changes were associated with significant decrease in body weight and increase in kidney weight. Serum creatinine and urea nitrogen were also elevated in all gentamicin treated rats [P<0.01]. In rats treated simultaneously with both gentamicin and either ibuprofen or diclefenac sodium for 5 days, all the measured parameters of renal dysfunction were similar in magnitude to those observed in rats treated with gentamicin alone. In contrast, rats treated with either ibuprofen or diclofenac sodium for 27 days and injected concurrently with gentamicin during the last 5 days of the treatment period had significantly greater kidney weight, lower renal cortical Na[ +/- ]K[ +/- ] ATPase activity and higher cortical phospholipid content, serum creatinine and urea nitrogen than did rats treated with gentamicin alone [P<0.05]. A 27 -day treatment with ibuprofen or diclofenac sodium alone resulted in no change in renal function. These results demonstrate that gentamicin nephrotoxicity was potentiated after the long [27 days] but not after the short [5 days] period of treatment with ibuprofen and diclofenac sodium. Thus, prolonged administration of NSAIDs even in therapeutic doses should be considered as a risk/actor that may increase the nephrotoxic potential of gentamicin

Histological study of early and late nephrotoxicity and endothelial cytotoxicity of ionic and non-ionic contrast media

The Structural changes induced by the use of radiopaque contrast media have been investigated using light and electron microscopic techniques. Three groups of adult male rats were used in this study. The first group [n=15] was injected intravenously with urographin in a dose of 0.5 ml/kg body weight. The second group [n=15] was injected with a similar dose of iopamidol. The third group [n=15] served as control. Specimens from the kidney and inferior vena cava were taken after 3,7 and 14 days of injection. Glomerular and tubular changes of the kidney and the endothelium of the inferior vena cava were evident after the use of both types of media. However, the effect was more pronounced and persistent after the use of ionic media. The results indicate that the tubular effect of the ionic media is secondary to its high osmolality and not to its inherent chemotoxicity. On the other hand, a chemotoxic effect on the glomerular epithelial cells [podocytes] is suggested. In addition, ischemia of the kidney is another factor that contributes to the nephrotoxic effect of the ionic media. Contrast media influenced the endothelium of the inferior vena cava indicating that the effect on the vascular endothelium extends to involve vessels distant from the site of injection