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Biomedical subjects

P Seth

Publications and source records attributed to P Seth.

At least 37 records · Page 2Linked to original sources
PubMed2001

Biochemical differences between SUDHL-1 and KARPAS 299 cells derived from t(2;5)-positive anaplastic large cell lymphoma are responsible for the different sensitivity to the antiproliferative effect of p27(Kip1).

An inverse correlation between p27(Kip1) expression and proliferation has been recently established in tissues derived from human lymphomas. The nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)/phospholipase C-gamma (PLCgamma) complex also appears to play an important role in cell proliferation and malignant transformation of anaplastic large cell lymphoma (ALCL). In this study, we report that SUDHL-1 and KARPAS 299 ALCL-derived cell lines present different sensitivity to the antiproliferative effect of recombinant adenovirus-mediated p27(Kip1) expression or to serum-starvation in culture media. The results indicate that exogenous p27(Kip1) may interact with the NPM-ALK/PLCgamma pathway in SUDHL-1 but not in KARPAS 299 cells. This interaction correlates with changes in cell cycle and cell morphology observed mainly in SUDHL-1 cells. The percentage of SUDHL-1 cells in S phase declines, whereas it is almost unchanged in KARPAS 299 cells as compared to the controls after 96 h of infection with the recombinant adenovirus. Furthermore KARPAS 299 cells are resistant to serum-starvation due to deficient p27(Kip1)-upregulation and G1 arrest, whereas SUDHL-1 cells respond with increased G1 phase and p27(Kip1)-upregulation after 48 h of serum-starvation. Both cell lines express appropriate variation of levels of cyclins E and A, and Rb-phosphorylation as expected by growing them in culture media with different FBS content. Although both cell lines express cyclin D2, SUDHL-1 cells only present high level of cyclin D3. Moreover SUDHL-1 cells express high level of PTEN and the PKB/Akt pathway is constitutively activated in both cell lines. Lastly SUDHL-1 cells show higher levels of phosphotyrosine-containing proteins that is correlated with a higher NPM-ALK-associated autophosphorylation activity compared to KARPAS 299 cells. Our study clearly identifies some of the biochemical differences that may explain the difference in sensitivity to antiproliferative stimuli shown by two cell lines derived from the same type of lymphoma.

Adenoviridae↗
PubMed2001

Expression pattern of the type 1 sigma receptor in the brain and identity of critical anionic amino acid residues in the ligand-binding domain of the receptor.

The type 1 sigma receptor (sigmaR1) has been shown to participate in a variety of functions in the central nervous system. To identify the specific regions of the brain that are involved in sigmaR1 function, we analyzed the expression pattern of the receptor mRNA in the mouse brain by in situ hybridization. SigmaR1 mRNA was detectable primarily in the cerebral cortex, hippocampus, and Purkinje cells of cerebellum. To identify the critical anionic amino acid residues in the ligand-binding domain of sigmaR1, we employed two different approaches: chemical modification of anionic amino acid residues and site-directed mutagenesis. Chemical modification of anionic amino acids in sigmaR1 with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide reduced the ligand-binding activity markedly. Since it is known that a splice variant of this receptor which lacks exon 3 does not have the ability to bind sigma ligands, the ligand-binding domain with its critical anionic amino acid residues is likely to be present in or around the region coded by exon 3. Therefore, each of the anionic amino acids in this region was mutated individually and the influence of each mutation on ligand binding was assessed. These studies have identified two anionic amino acids, D126 and E172, that are obligatory for ligand binding. Even though the ligand-binding function was abolished by these two mutations, the expression of these mutants was normal at the protein level. These results show that sigmaR1 is expressed at high levels in specific areas of the brain that are involved in memory, emotion and motor functions. The results also provide important information on the chemical nature of the ligand-binding site of sigmaR1 that may be of use in the design of sigmaR1-specific ligands with potential for modulation of sigmaR1-related brain functions.

Amino Acid Motifs↗
PubMed2001

Increased expression of p27Kip1 arrests neuroblastoma cell growth.

BACKGROUND AND PROCEDURE: To investigate the molecular mechanisms by which retinoic acid (RA) alters cell growth, the expression and activity of components of the cell cycle machinery were analyzed. RESULTS AND CONCLUSIONS: Within 2 days of RA treatment, and prior to the arrest of NB cells in the G1 phase of the cell cycle, there was a complete downregulation of GI cyclin/cdk activities. Protein levels for the G1 cyclin/cdk were essentially unchanged during this time, although there was a decrease in the steady state levels of hyperphosphorylated Rb and p60N-MYC proteins. The cdk inhibitors, p21Cip1 and p27Kip1 were constitutively expressed in KCNR, while p15 INK4B and p16 INK4A mRNA were undetected. Within 24 hr of RA treatment, there was a 4-fold increase in the expression of p27Kip1, although p27 mRNA levels were unchanged. Levels of p21Cip1 were unaltered. Coincident with the decrease in kinase activity there was an increase in p27 bound to G1 cyclin/cdk. The increase in p27 was not due to an increase in transcription. In other cell systems, increased expression of c-MYC has been shown to lead to a decrease in p27 levels that is regulated at the post-transcriptional level (sequestration). To determine whether increased levels of N-MYC could affect the level of p27, we evaluated the expression of p27 in a series of N-MYC transfected cells and found that constitutive overexpression of N-MYC led to a decrease in the steady-state levels of p27 and in p27 bound to G1 cyclin/cdk complexes. Using adenoviral vectors expressing p27, we found that infection leads to increased p27 expression, which causes a decrease in cdk activity and an accumulation of cells in G1.

Adenoviridae↗
PubMed2001

Von Hippel-Lindau gene therapy: a novel strategy in limiting endothelial cell proliferative activity.

There is evidence that loss of function of the von Hippel-Lindau (VHL) gene causes transcriptional activation of the vascular endothelial growth factor (VEGF) gene, which in turn may lead to increased proliferation of vascular endothelial cells. We hypothesized that transfer of VHL gene, a tumor suppressor gene, into vascular endothelial cells could cause loss of viability and suppression of its proliferative ability. Human aortic endothelial cells (HAEC) were grown as monolayers and transfected with varying titers of adenovirus containing the VHL cDNA (AdVHL). The negative controls used were adenovirus containing green fluorescent protein (AdGFP), vector alone (AdNull), and infection medium without virus. Adenovirus encoding p53 (Adp53) was used as positive control. Cell viability and proliferation were determined by trypan blue dye exclusion and by a tetrazolium-based colorimetric assay. All experiments were performed in triplicate. Our results showed that proliferative activity in HAEC can be blocked and viability of HAEC reduced by adenovirus-mediated gene transfer of VHL gene. This is the first time that VHL gene has been effectively transferred to HAEC. VHL gene transfer into the vascular endothelium may have potential in limiting proliferative processes, including intimal hyperplasia.

Adenoviridae↗
PubMed2001

Synthesis and QSAR studies in 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives as potential antithrombotic agents.

A series of 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives have been synthesized via cyclocondensation of N-aryl thioureas with 2-bromoethylamine hydrobromide followed by the reaction of the product thus obtained with aroyl chlorides. Title compounds were evaluated for their antithrombotic activity in vivo in mice where one of these compound 29 provided 65% protection as compared to 77% protection offered by the standard Indomethacin. Quantitative Structure-Activity Relationship (QSAR) studies were performed on these compounds using physicochemical (hydrophobic, electronic, steric) parameter as independent and antithrombic activity as dependent parameter, where antithrombotic activity correlated best (r > 0.8) with electronic parameters (F, sigma or mu) having high statistical significance > 99.9% (F(2,22)>15.0; F(2,22alpha:0.001)=11.0) suggesting that hydrophobic, steric and resonance factors are insignificant in this set of molecules for the activity.

Animals↗
PubMed2001

Comparison of the effects of recombinant adenovirus-mediated expression of wild-type p53 and p27Kip1 on cell cycle and apoptosis in SUDHL-1 cells derived from anaplastic large cell lymphoma.

Recombinant adenoviruses expressing wild-type p53 (AdWTp53) and p27KiP1 (Adp27) were used to compare the effects on cell cycle and apoptosis in SUDHL-1 cells derived from human anaplastic large cell lymphoma. Cells infected with AdWTp53 and Adp27 showed high level of wild-type p53 and p27KiP1 expression, respectively. The expression of these proteins resulted in G1 arrest after 24 h of infection. Although the cells persisted in G1 arrest in both cell populations after 48 and 72 h of infection, the level of apoptosis assessed by TUNEL analysis was higher in cells infected with AdWTp53. Interestingly, apoptosis was more pronounced in cells infected with Adp27 after the initial 24 h and reached a steady state at 48 and 72 h. A lower MOI of Adp27 resulted in G1 arrest associated with a low level of apoptosis in SUDHL-1 cells after 48 h of infection. This was correlated with lower expression of p27KiP1. We postulate that the time-lag and the different level of apoptosis occurring in SUDHL-1 cells infected with AdWTp53 and Adp27 are clearly related to the intrinsic biochemical pathways solicited. In this context our study provides a model to investigate these pathways and better understand the biology of this particular lymphoma. Our data also support a potential application of Adp27 for gene therapy of this lymphoma similarly to AdWTp53 as previously shown.

Adenoviridae↗
PubMed2001

Multifaceted regulation of cell cycle progression by estrogen: regulation of Cdk inhibitors and Cdc25A independent of cyclin D1-Cdk4 function.

Estrogens induce proliferation of estrogen receptor (ER)-positive MCF-7 breast cancer cells by stimulating G(1)/S transition associated with increased cyclin D1 expression, activation of cyclin-dependent kinases (Cdks), and phosphorylation of the retinoblastoma protein (pRb). We have utilized blockade of cyclin D1-Cdk4 complex formation through adenovirus-mediated expression of p16(INK4a) to demonstrate that estrogen regulates Cdk inhibitor expression and expression of the Cdk-activating phosphatase Cdc25A independent of cyclin D1-Cdk4 function and cell cycle progression. Expression of p16(INK4a) inhibited G(1)/S transition induced in MCF-7 cells by 17-beta-estradiol (E(2)) with associated inhibition of both Cdk4- and Cdk2-associated kinase activities. Inhibition of Cdk2 activity was associated with delayed removal of Cdk-inhibitory activity in early G(1) and decreased cyclin A expression. Cdk-inhibitory activity and expression of both p21(Cip1) and p27(Kip1) was decreased, however, in both control and p16(INK4a)-expressing cells 20 h after estrogen treatment. Expression of Cdc25A mRNA and protein was induced by E(2) in control and p16(INK4a)-expressing MCF-7 cells; however, functional activity of Cdc25A was inhibited in cells expressing p16(INK4a). Inhibition of Cdc25A activity in p16(INK4a)-expressing cells was associated with depressed Cdk2 activity and was reversed in vivo and in vitro by active Cdk2. Transfection of MCF-7 cells with a dominant-negative Cdk2 construct inhibited the E(2)-dependent activation of ectopic Cdc25A. Supporting a role for Cdc25A in estrogen action, antisense CDC25A oligonucleotides inhibited estrogen-induced Cdk2 activation and DNA synthesis. In addition, inactive cyclin E-Cdk2 complexes from p16(INK4a)-expressing, estrogen-treated cells were activated in vitro by treatment with recombinant Cdc25A and in vivo in cells overexpressing Cdc25A. The results demonstrate that functional association of cyclin D1-Cdk4 complexes is required for Cdk2 activation in MCF-7 cells and that Cdk2 activity is, in turn, required for the in vivo activation of Cdc25A. These studies establish Cdc25A as a growth-promoting target of estrogen action and further indicate that estrogens independently regulate multiple components of the cell cycle machinery, including expression of p21(Cip1) and p27(Kip1).

Adenoviridae↗
PubMed2001

Seroepidemiology and active surveillance of dengue fever/dengue haemorrhagic fever in Delhi.

The aims of the present study were to carry out surveillance for dengue virus infection in adults with short-duration fever, and serological study of dengue virus infection in persons without fever. Patients were divided into two groups. Group 1 included patients above 12 years of age with fever of 2-12 days duration without any apparent cause. Of these, patients who presented with fever for 2-5 days were included for virus isolation (group 1a) while those who presented within 6-12 days of the onset of fever were included for the dengue-specific IgM serology (group 1b). Group 2 included a sample of population belonging to all age groups but without pyrexia and blood was collected for dengue-specific IgG serology. Twenty-six patients were enrolled in group 1a over a period of 4 months (September to December, 1997). Of these, DEN1 was isolated in 5 cases. Group 1b included 182 patients, out of which 34 (18.68%) were positive for dengue-specific IgM antibodies. Significantly, all the positive cases were detected during the months of September to November. Retro-orbital pain was present in a significantly more number of IgM-positive cases as compared to IgM-negative cases. Group 2 included 125 cases without fever. The overall positivity for dengue-specific IgG antibodies was 77.6%, with the highest positivity of 100% in the age group of 31-40 years. It was concluded that dengue virus infection is endemic in and around Delhi with peak incidence between September and Novemver. The prevalent serotype during September and December 1997 was DEN1. Since previous epidemic of DHF was due to DEN2 type, isolation of DEN1 serotype indicates changes of another epidemic of DHF due to DEN1 serotype. The stresses the urgent need for implementation of measures to control the transmission of dengue infection.

Adult↗
PubMed2001

Use of nucleotide sequencing of the genomic cDNA fragments of the capsid/premembrane junction region for molecular epidemiology of dengue type 2 viruses.

The recent emergence of dengue hemorrhagic fever/dengue shock syndrome (DHF/ DSS) in India has been a source of concern. In the present study a quantitative comparison of 406 nucleotide long sequence from the capsid-premembrane junction region (C-PrM) of 9 dengue virus type 2 (DEN-2) isolates from Delhi with 10 DEN-2 isolates from diverse geographic areas provided sufficient information for estimating genetic relationships. The data indicated that the 1996 epidemic of DHF in Delhi was caused by genotype IV strains of DEN-2. This genotype, perhaps, displaced genotype V strains of DEN-2, which was circulating genotype in 1967. The period during which this displacement had occurred is not clear from the present study. Nonetheless, similar experience in four countries in Latin America and in Sri Lanka suggest that the introduction of new genotypes of DEN-2 displacing the circulating genotype may be associated with the appearance of DHF/DSS. More work is required to elucidate this hypothesis. Transitions at nucleotide positions 406 and 431 resulted in amino acid substitutions near (aa position 104, methionine --> valine) and at the hinge region (aa position 112, valine --> alanine) of C-PrM, respectively in all/most genotypes of group III and IV DEN-2 viruses analysed. Most of these virus strains have been isolated from DHF/DSS outbreaks. Significance of this observation is discussed. The data presented in this study suggest the utility of C-PrM sequence analysis for molecular epidemiology of dengue viruses.

Adolescent↗
PubMed2001

Immunization with HIV-1 subtype B gp160-DNA induces specific as well as cross reactive immune responses in mice.

BACKGROUND & OBJECTIVES: HIV-1 gp160 is an important structural protein for the virus cell interaction and virus entry. Therefore, it is regarded as the most important target for HIV-1 vaccine development. In this study we investigated the use of HIV-1 gp160-DNA construct in eliciting specific and cross reactive cell mediated immune response in mice. METHODS: DNA segment encoding env, tat and rev genes of HIV-1 subtype B (strain BRU-2) was amplified and cloned into mammalian expression vector pCI to generate plasmid pCIBRU-TRE. Mice were injected intramuscularly four times at biweekly intervals with 100 micrograms/dose of pCIBRU-TRE in normal saline, and subsequently analysed for anti HIV-envelope (env) immune responses. RESULTS: A low antibody level was detected as determined by ELISA after 4 doses. Subsequent inoculations failed to increase the antibody titres significantly. Spleen cells from the immunized mice were used for the detection of cellular immune response by lymphocyte proliferation assays (LPA), in vitro production of cytokines and cytotoxic T lymphocyte (CTL) assays. T cell response which was seen from the second week onwards, persisted even at the end of 24 wk following the last dose. Similar levels of T cell proliferation were observed on stimulation with either homologous or heterologous peptides. Cytokine studies showed a Th1 type of response. A cross clade MHC class I restricted CTL response was observed against target cells stimulated with either homologous or heterologous HIV antigens. INTERPRETATION & CONCLUSION: This study demonstrated that DNA encoding full length HIV-1 env glycoprotein gp160 induces specific as well as cross reactive cell mediated immune responses in mice. However, the induction of antibody response was poor.

AIDS Vaccines↗
PubMed2001

Comparative evaluation of various commercial assays for diagnosis of dengue fever.

Dengue fever (DF) is endemic in India and dengue hemorrhagic fever (DHF) has been reported with increasing frequency in the last decade. We evaluated three commercial assays for detection of antibodies to dengue virus, to assess their performance in a diagnostic laboratory. Sera from 58 patients collected during a febrile outbreak in New Delhi in 1997 were studied. The methods evaluated were MRL Diagnostic Dengue Fever Virus IgM Capture ELISA, Pan Bio Dengue Duo IgM and IgG Capture ELISA and Pan Bio Rapid Immunochromatographic test. The MRL ELISA correctly identified 97.8% (43 of 44) of samples as dengue positive while the Pan Bio Duo ELISA and Pan Bio RIT identified 95.45% (42 of 44). The sensitivities of both Pan Bio Duo ELISA and Pan Bio RIT for primary dengue and secondary dengue were 100% and 93.54% respectively. The specificity of three assays were MRL IgM ELISA 100%, Pan Bio Duo ELISA 92.8% and Pan Bio RIT 85.7%.

Dengue↗
PubMed2001

Evaluation of a dipstick ELISA and a rapid immunochromatographic test for diagnosis of Dengue virus infection.

Here we report standardization of a dipstick enzyme-linked immunosorbent assay (ELISA, Dipstick ELISA) and its comparative evaluation with a commercial Rapid PanBio Immunochromatographic test (IC test) for detection of Dengue (DEN) virus-specific IgM and IgG antibodies in patient sera. Among crude and purified viral antigens prepared from mouse brains or cell cultures, a DEN virus type 2 antigen purified from cell cultures by sucrose density gradient centrifugation was found superior in terms of the signal/ noise (S/N) ratio in the assay system. The sensitivity of detection of the virus by specific IgM antibody was improved by removal of IgG from patient sera prior to testing. The evaluation of the Dipstick ELISA by use of 156 serum samples revealed an overall accordance of 96% and 93% with the IC test in detection of IgM antibodies to DEN viruses (IgM antibodies) and IgG antibodies to DEN viruses (IgG antibodies), respectively. The sensitivity of the Dipstick ELISA and the IC test with reference to the mu-capture ELISA was 83% and 87%, respectively, with a specificity of 98% in both cases. The sensitivity of the Dipstick ELISA with reference to the IC test in detecting IgM and IgG antibodies was 84% and 94%, respectively, and the specificity of the Dipstick ELISA was 98% and 92%, respectively.

Animals↗
PubMed2000

Phenol sulfotransferases: hormonal regulation, polymorphism, and age of onset of breast cancer.

In recent years, significant effort has been made to identify genes that influence breast cancer risk. Because the high-penetrance breast cancer susceptibility genes BRCA1 and 2 play a role only in a small fraction of breast cancer cases, understanding the genetic risk of the majority of breast cancers will require the identification and analysis of several lower penetrance genes. The estrogen-signaling pathway plays a crucial role in the pathophysiology of breast cancer; therefore, polymorphism in genes involved in this pathway is likely to influence breast cancer risk. Our detailed analysis of gene expression profiles of estrogen- and 4-OH-tamoxifen-treated ZR75-1 breast cancer cells identified members of the sulfotransferase 1A (SULT1A) phenol sulfotransferase family as downstream targets of tamoxifen. On the basis of the induction of SULT1A by 4-OH-tamoxifen and the known inherited variability in SULT1A enzymatic activity, we hypothesized that polymorphism in sulfotransferase genes might influence the risk of breast cancer. Using an RFLP that distinguishes an arginine to histidine change in exon 7 of the SULT1A1 gene, we characterized SULT1A1 genotypes in relation to breast cancer risk. An analysis of 444 breast cancer patients and 227 controls revealed no effect of SULT1A1 genotype on the risk of breast cancer (P = 0.69); however, it did appear to influence the age of onset among early-onset affected patients (P = 0.04). Moreover, individuals with the higher activity SULT1A1*1 allele were more likely to have other tumors in addition to breast cancer (P = 0.004; odds ratio, 3.02; 95% confidence interval, 1.32, 8.09). The large number of environmental mutagens and carcinogens activated by sulfotransferases and the high frequency of the SULT1A1*1 allele in human populations warrants additional studies to address the role of SULT genes in human cancer.

Adult↗
PubMed2000

p53-dependent induction of heat shock protein 27 (HSP27) expression.

Transcriptional activation of the p53 target genes plays a critical role in the cellular response to DNA damage, hypoxia, cellular stress and other signals regulating the cell cycle and apoptosis. The discovery of new p53 target genes continues to reveal novel mechanisms of action of this multifaceted protein. We used cDNA arrays to search for p53-regulated genes in prostate cancer cells. In this report, we describe robust induction of heat shock protein 27 (hsp27) in prostate cancer cells (DU145, LNCaP, PC3) following wild-type p53 expression from an adenoviral p53 expression vector (AdWTp53). A mutant p53 (R175H)-containing adenoviral expression vector did not induce hsp27. hsp27 expression was not altered in prostate cancer cells following expression of cyclin-dependent kinase inhibitors: p21(waf1/cip1) and p27(kip1) from adenoviral expression vectors. Treatment of cells with staurosporine, an apoptosis-inducing agent, did no affect hsp27 expression. These observations provide evidence that induction of hsp27 expression was wild-type p53-specific and was not due to non-specific effects of cell growth arrest and/or apoptosis. Previous studies and the experiment reported here show induction of hsp27 expression in response to androgen ablation, a physiological state that induces apoptosis in prostatic epithelial cells. The nature of p53 and hsp27 interactions in the regulation of apoptosis and/or cell growth needs to be further defined.

Adenoviridae↗
PubMed2000

Polymerase chain reaction in clinically suspected genitourinary tuberculosis: comparison with intravenous urography, bladder biopsy, and urine acid fast bacilli culture.

OBJECTIVES: To evaluate the role of urinary polymerase chain reaction (PCR) in the detection of Mycobacterium tuberculosis (MTb) in patients with a clinical suspicion of genitourinary tuberculosis (GUTB) and to compare its sensitivity with intravenous urography (IVU), bladder biopsy, and urine culture for acid fast bacilli (AFB). METHODS: The study was carried out between September 1997 and December 1998 in 42 patients with a clinical suspicion of GUTB. Their clinical features, organ involvement, and investigation results were studied. The diagnostic yield of urinary PCR for MTb and its sensitivity in comparison with routine urine AFB culture, bladder biopsy, and IVU were assessed. RESULTS: There were 25 male and 17 female patients, with a mean age of 31.04 years. Patients suspected of having GUTB most often presented with irritative voiding symptoms. Two patients had abnormal renal parameters. Of the 42 patients clinically suspected of having GUTB, radiologic abnormalities suggestive of GUTB were found in 37 (88.09%); MTb was isolated in the urine AFB culture in 13 (30.95%); bladder biopsy was positive in 11 (45.83%); and urinary PCR for MTb was positive in 34 cases (80.95%). Of 35 cases of proven GUTB, IVU was suggestive of the diagnosis in 32 (91.42%) and MTb was isolated in the urine AFB culture in 13 cases (37.14%). Bladder biopsy was positive in 11 (45. 83%) of 24 patients in whom biopsy was taken, and urinary PCR for MTb was positive in 33 (94.29%). CONCLUSIONS: A high index of suspicion is necessary for a diagnosis of GUTB. In clinically suspected cases, IVU may be suggestive of GUTB, but it is not specific. In the present study, IVU was suggestive in 88.09% of patients. MTb was isolated in the urine AFB culture in only 37.14% of patients, and bladder biopsy was positive in 45.83%. Urinary PCR for MTb was the most sensitive indicator and was positive in 94.29% of patients. It is evident from this series that PCR provides a much faster diagnosis of urinary MTb. It is a rapid, sensitive, and specific diagnostic method and avoids a delay in starting treatment.

Adolescent↗
PubMed2000

Prevention of renal ischemia-reperfusion-induced injury in rats by picroliv.

Picroliv is a potent antioxidant extracted from the roots and rhizome of Picrorhiza kurrooa. It has been shown to impart significant hepatoprotective activities, partly by modulation of free radical-induced lipid peroxidation. Lipid peroxidation and reactive oxygen species are associated with tissue injury in post-ischemic acute renal failure. The efficacy of picroliv was assessed in an in vivo model of renal ischemia-reperfusion injury (IRI) in rats at a dose of 12 mg/kg orally for 7 days. The animals were killed at various times after reperfusion. Increased lipid peroxidation and apoptotic cell number reflected the oxidative damage following renal IRI. Picroliv-pretreated rats exhibited lower lipid peroxidation, improved antioxidant status, and reduced apoptosis, indicating better viability of renal cells. Immunohistochemical studies revealed that picroliv pretreatment attenuated the expression of intercellular adhesion molecule-1 in the glomerular region. These results suggested that picroliv pretreatment protects rat kidneys from IRI, perhaps by modulation of free radical damage and adhesion molecules.

Animals↗