Effect of quercetin against dichlorvos induced nephrotoxicity in rats

This study was carried out to determine the effect of quercetin against renal injury induced by dichlorvos (DDVP) in rats. Rats were randomly assigned to control, DDVP-treated (7.2 mg/kg bw), three different doses of quercetin-treated (2 mg/kg bw, 10 mg/kg bw, 50 mg/kg bw) and different doses of quercetin plus DDVP-treated groups. DDVP was administered daily to rats through their drinking water, and quercetin was administered by intragastric gavage for 90 days. By the end of the 90th day in the DDVP-treated group, the following indices significantly increased compared with the control (P < 0.01): activities of catalase, glutathione peroxidase and superoxide dismutase; level of malondialdehyde in kidney tissues; serum levels of creatinine and urea nitrogen; and level of β2-microglobulin, level of retinol-conjugated protein, and activity of N-acetyl-β-d-glucosaminidase in urine; by contrast, urine uric acid levels significantly decreased. However, in the quercetin (50 mg/kg bw) plus DDVP group, the aforementioned indices were significantly decreased compared with the DDVP-treated group (P < 0.05), except the urine uric acid levels were significantly increased (P < 0.05). Thus, rat exposure to DDVP caused renal injury, including renal tubular, glomerular filtration, and oxidative stress. These toxic effects were also regulated by high-dose quercetin. Histopathological examination revealed that exposure to DDVP induced extensive cell vacuolar denaturation, but milder histopathological alterations in the kidney tissues of rats co-treated with DDVP and quercetin (50 mg/kg bw) were observed. These results indicated that quercetin at 50 mg/kg bw can partly prevent the kidney injury induced by DDVP.     

Protective effect of Moringa oleifera leaves against gentamicin-induced nephrotoxicity in rabbits

Oxidative stress due to abnormal production of reactive oxygen species has been implicated in the nephrotoxicity induced by gentamicin. The nephroprotective effect of aqueous-ethanolic extract of Moringa oleifera leaves (150 and 300 mg/kg) was evaluated against gentamicin-induced (80 mg/kg) renal injury in rabbits. Serum urea and creatinine levels were evaluated as the markers of renal nephrotoxicity. At the end of the experiment, the kidneys of rabbits were excised for histological examinations and determination of lipid peroxidation levels. Serum urea and creatinine levels were reduced in the M. oleifera (150 and 300 mg/kg) plus gentamicin treated groups. On histological examinations, kidney of intoxicated rabbits groups which received M. oleifera extract showed reparative tendencies. A highly significant (p < 0.01) elevation was observed in lipid peroxidation (LPO) level in the kidneys of gentamicin-intoxicated rabbits whereas combined treatment of M. oleifera and gentamicin group showed a highly significant (p < 0.01) depletion in LPO. The present study indicates that aqueous-ethanolic extract of M. oleifera leaves attenuates renal injury in rabbits treated with gentamicin, possibly by inhibiting lipid peroxidation.     

Carvedilol exacerbate gentamicin-induced kidney mitochondrial alterations in adult rat

Gentamicin is an aminoglycoside antibiotic widely used to treat many types of bacterial infections. Although its properties, his clinical use is limited due to the occurrence of nephrotoxicity, which has been related to mitochondrial dysfunction. Carvedilol, an antihypertensive drug with strong antioxidant properties, has been tested in order to prevent gentamicin nephrotoxicity. This study aimed to test this hypothesis using a rat model of gentamicin-induced nephrotoxicity. Animals were treated subcutaneously with DMSO (control) (0.4%/kg/24 h bw) for 11 days; with carvedilol (2 mg/kg/24 h bw) for 11 days; with gentamicin (60 mg/kg/24 h bw) for the last 8 days and with carvedilol (2 mg/kg/24 h bw) for 11 days and with gentamicin (60 mg/kg/24 h bw) for the last 8 days. Estimations of urine creatinine, urine carboxylic acids, blood urea, serum creatinine and glomerular filtration rate were carried out after the last administered dose of gentamicin. Mitochondria functionality was analyzed by monitoring its bioenergetics function and cardiolipin oxidized products were analyzed by ESI–MS. The kidneys were also examined for morphological changes. Gentamicin caused marked nephrotoxicity and mitochondrial dysfunction as evidenced by several mitochondrial parameters. Carvedilol did not induce significant changes while the co-treatment exacerbated the negative effect of gentamicin although maintaining ATP levels and membrane potential. Kidneys from gentamicin treated rats, with and without carvedilol, showed necrosis of tubular cells in renal cortex. Higher values on relative abundance of cardiolipin oxidation products identified as [M-2H]^2? ions, at m/z 771 were observed in the groups treated with gentamicin. The observed effects were associated to a possible interaction of carvedilol with F₁F₀-ATP synthase that merit further investigation. In conclusion, carvedilol may contribute to the exacerbation of renal dysfunction induced by gentamicin, at least in some physiological and biochemical parameters. From a clinical perspective, and until further conclusions, cautious use of both drugs in combination is advised with particular emphasis in patients presenting mitochondrial disorders.     

The effect of experimental long-term exposure to low-dose zearalenone on uterine histology in sexually immature gilts

The objective of this study was to determine whether long-term (48-day) oral administration of low-dose zearalenone (ZEA) resulted in changes in uterine histology in sexually immature gilts. The study involved 12 clinically healthy 2-month-old gilts with a determined immune status. The animals were randomly divided into two experimental groups (E1, n = 4; E2, n = 4) and a control group (C, n = 4). ZEA (20 μg/kg bw for group E1 and 40 μg/kg bw for group E2) was administered in gelatin capsules per os before the morning feeding for 48 days; group C was given placebo rather than ZEA. The animals were then sacrificed and the uteri were subjected to histological examination. Low doses of ZEA (50% and 100% of no observable adverse effect levels values) induced experimental hyperestrogenism and stimulated the proliferation of nearly all uterine wall tissues, as shown by significant increases in the index of proliferation values. The accompanying uterine hyperaemia caused uterine reddening and swelling. Atypical endometrial hyperplasia (hyperplasia simplex atypica) could be interpreted as the endometrium's physiological response to an excessive level of endogenous and/or exogenous estrogenic stimuli. The results of this study and the effects of ZEA in the uterus suggest that there is a possibility of detrimental health effects when the level of endogenous estrogens is low and the body is supplied with an additional dose of exogenous estrogens. Such effects probably results from synergic interaction that produce hyperestrogenism and lead to excessive estrogenic stimulation.     

Effects of melatonin on lipid peroxidation and antioxidative enzyme activities in the liver,kidneys and brain of rats administered with benzo(a)pyrene

Benzo(a)pyrene [B(a)P] is a widespread pollutant with a mutagenic, carcinogenic and strong prooxidative properties. The present study evaluated the melatonin effects on lipid peroxidation products levels and on activity of antioxidative enzymes in the course of B(a)P intoxication. Control rats were treated with 0.9% NaCl; another group was given 10 mg melatonin/kg bw; a third group was injected twice a week with B(a)P at the dose of 10 mg/kg bw; the fourth group received both B(a)P and melatonin at the dose as mentioned above. The experiment continued for 3 months. In homogenates of brain, liver and kidneys lipid peroxidation was appraised by evaluation of malonyldialdehyde and 4-hydroxyalkenal (MDA+4HDA) levels. Activities of glutathione peroxidase (GPx), superoxide dysmutase (SOD) and catalase (CAT) and concentration of reduced glutathione (GSH) were also estimated. In animals receiving both B(a)P and melatonin, lower levels of MDA+4HDA were observed in all organs as compared to the group treated with B(a)P only. Following administration of B(a)P, GSH level decreased in brain and kidney. Melatonin in combination with B(a)P induced rises in the GSH level in liver and brain, as compared to the receiving B(a)P alone. The activity of SOD increased in the rats treated with melatonin alone but the highest activity was observed in rats treated with B(a)P plus melatonin. CAT activity in the melatonin-treated group increased in brain and liver. Similar to SOD, activity of the enzyme significantly increased in the group treated in combination with B(a)P and melatonin, as compared to the remaining groups in all tested tissues. The results suggest that melatonin protects cells from the damaging action of B(a)P. According to our knowledge, there are no studies describing the effects of melatonin on lipid peroxidation markers and antioxidative enzymes during intoxication of B(a)P in the brain, liver and kidneys. The results of present study give a perspective for further studies of its free radical scavenger properties in prevention of oxidative stress dependent diseases, among others cancers caused by carcinogens such as B(a)P.     

Effect of vitamin C in reducing the toxicity of endosulfan in liver in rabbits

In this study, the effect of endosulfan, an organochlorine pesticide, and the ameliorating effect of vitamin C on the livers of New Zealand white rabbits were studied. Livers of the rabbits were examined grossly and histopathologically, and caspase-3 activity was detected by immunohistochemical methods. A total of twenty-four rabbits were divided into four groups (n=6). Rabbits in Group I (END) were daily given a sublethal dose of endosulfan (1 mg/kg bw) in corn oil by oral gavage for 6 weeks. Group II (END+C) received the same dose of endosulfan and additionally Vit C (20 mg/kg bw) every other day during this period. Group III (OIL+C) received corn oil daily by oral gavage and vitamin C every other day for 6 weeks. Group IV (OIL), the control group, received only corn oil daily, by oral gavage throughout the experiment. The concentration of α-endosulfan in the END group was higher in livers (0.102±0.012 ppb) than the β-endosulfan (0.072±0.001 ppb). Decreased accumulation of α and β endosulfan was observed in the END+C group (0.025±0.003 and 0.016±0.002 ppb, respectively) (p<0.0001). The most prominent gross findings at the necropsy were seen in the END group, in which swollen and pale livers were commonly observed. Hemorrhages, degenerations, necrosis, and in some rabbits bile duct hyperplasia were the marked histopathological findings of the END group. Caspase-3 positive reaction was more severe in this group than in the others. An ameliorating effect of Vit C on gross, histopathological and immunohistochemical findings was observed in the END+C group. The results revealed that endosulfan is highly toxic for rabbit livers. However, toxicity was decreased by Vit C treatment, which reduced the accumulation of endosulfan in livers four-fold.     

Toxico-pathological changes induced by cypermethrin in broiler chicks: Their attenuation with Vitamin E and selenium

Ninety 1-day old broiler chicks of mixed gender (as hatched) procured from a local hatchery were randomly divided into five equal groups. All the treatments were given through crop tubing. Groups 1–4 received cypermethrin (CY) (600 mg kg^?1 b. wt.) daily for 30 days. In addition to CY (group 1), groups 2–4 received Vit E (150 mg kg^?1 b. wt.), Se (0.25 mg kg^?1 b. wt.), and Vit E (150 mg kg^?1 b. wt.)+Se (0.25 mg kg^?1 b. wt.), respectively. Group 5 served as control andreceived normal saline (2 ml kg^?1 b. wt.) for 30 days. Randomly selected six broiler chicks from each group were slaughtered at experimental days 10, 20 and 30 for the collection of serum/plasma and morbid tissues. Absolute organ weights were recorded. Total plasma proteins, fibrinogen and creatinine were significantly (P<0.05) increased while alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and urea decreased significantly (P<0.05) in CY-treated group when compared with the control group. Kidneys were swollen grossly in treated broiler chicks. In liver, necrosis of hepatocytes, cytoplasmic vacuolation, bile duct hyperplasia and mononuclear cellular infiltration were observed. In kidneys, necrosis of tubular epithelial cells, cytoplasmic vacuolation, cellular infiltration and atrophy of glomeruli were observed. Sub-arachnoid space was much dilated in CY-treated broiler chicks. It can be concluded that CY induces biochemical and histopathological alterations in broilers chicks; however, these toxic effects can be ameliorated by Vit E or Se. Combination of Vit E and Se was more effective in ameliorating toxic effects of cypermethrin in broilers chicks.     

Biochemical and histopathological evaluation of histamine receptors (H1R,H2R,H3R and H4R)-agonist in rabbits

The present study was designed to investigate the biochemical and histopathological changes in the livers of rabbits treated with histamine and histamine receptors (H1R–H4R)-agonist. The cohort comprised of six groups containing five rabbits each. Control group received sterile distilled water (1 mL/kg × b.i.d.) and treated groups received subcutaneous histamine (100 μg/kg × b.i.d.) and H1R–H4R-agonist (histamine trifluoro-methyl toluidide, amthamine, R-[?]-α-methylhistamine, clobenpropit, respectively) each in a dose of 10 μg/kg × b.i.d. (12 h [8 am and 8 pm]) for 30 days. Hepatotoxicity due to these agonists was analyzed using biochemical and histopathological methods. Histamine and H1R–H3R-agonist were found to be hepatotoxic as shown by statistically significant (p < 0.05) elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), most marked in the H3R-agonist group. However, their levels in H4R-agonist group remained very similar to the control group. The entire drug treated groups as compared to control showed significant elevated levels of alkaline phosphatase (ALP). Histopathological examination revealed obvious changes in histamine, H2R- and H3R-agonist groups in terms of alteration of hepatic microstructure, congestion, focal necrosis and increased incidence of multinucleate hepatocytes while H1R and H4R groups showed minimal changes. From the findings of the present study it may be concluded that on repeated administration, histamine and HR-agonists-induced hepatotoxicity which is most pronounced with H3R-agonist though not severe enough to jeopardize the vital functions of liver and warrants further long-term studies.     

Short-term increase of serum troponin I and serum heart-type fatty acid-binding protein (H-FABP) in dogs following administration of formoterol

In this paper, changes in serum levels of the cardiac biomarkers troponin I and the heart-type fatty acid-binding protein (H-FABP) following administration of a long-acting β₂-sympathicomimeticum (long-acting beta-agonist, LABA) to dogs were measured.We measured troponin I in dogs in a 4-week repeated-dose study with inhalative administration of formoterol (13 μg/kg d) and a glucocorticoid/formoterol combination (143/16 μg/kg d). The medians of troponin I increased within 3 days in both groups, far beyond the cut-off level (0.1 μg/L), but returned to baseline levels on study day 9. The increase was more pronounced in the formoterol-only group (3.29 μg/L) compared to the glucocorticoid/formoterol combination group (1.32 μg/L).In a second study, we measured serum troponin I as well as serum H-FABP levels in several samples over 7 days in dogs, receiving a single inhalative dose of a glucocorticoid/formoterol combination (120/12 μg/kg d). The median of the troponin I concentration increased above the cut-off level within 2 h and that of H-FABP within 4 h. The medians of both parameters were temporarily above the cut-off levels even on study day 7.Both studies were conducted according to national animal welfare guidelines.To our knowledge, this is the first report that shows a corresponding increase of troponin I and H-FABP in dogs treated with formoterol. Both parameters are more sensitive in detecting a drug-induced cardiac injury compared to total LDH, total CK as well as CK MB activity. However, it is recommended to take at least three blood samples per day to assess a temporary increase of troponin I.     

Elevation of urinary globotriaosylceramide (GL3) in infants with Fabry disease

BackgroundFabry disease is caused by a deficiency of α-galactosidase A (α-Gal A), which results in the accumulation of globotriaosylceramide (GL3) and related glycosphingolipids in different organs. Urinary GL3 levels increase in symptomatic Fabry disease patients, but it is not clear whether urinary GL3 excretion also increases in young or pre-symptomatic patients.Subjects and methodsEighty-nine newborns with leukocyte α-Gal A activities of less than 30% of the normal mean were discovered by newborn screening. Urine samples were collected on filter paper, and GL3 levels were measured using liquid chromatography–tandem mass spectrometry.ResultsFive newborns with classic Fabry disease mutations all had elevated urinary GL3 levels (mean = 5.2 mg/mmol creatinine (creat.), range = 0.80–14.39, normal < 0.6). Among the 84 newborns with later-onset mutations, 45 (54%) had a mild elevation of urinary GL3 levels (mean = 1.1 mg/mmol creat., range = 0.60–3.07, normal < 0.6). The urinary GL3 levels decreased in all newborns over the course of a three-year follow-up period. However, four children with classic mutations and seven with IVS4+919G>A mutations still had elevated GL3 levels at the end of the study.ConclusionElevated urinary GL3 levels can be present at birth in Fabry disease patients, suggesting an early involvement of the kidneys in this disease. The increased urinary GL3 excretion in those with later-onset mutations supports a pathogenic role for these mutations.     

New insight in colistin induced neurotoxicity with the mitochondrial dysfunction in mice central nervous tissues

In the present study, the mechanism of colistin-induced neurotoxicity was investigated with a focus on behavioral characters, mitochondrial ultrastructures and functions of the central nerve tissues in mice followed by administrating intravenously 15 (divided into two dose and 12 h apart), 7.5 and 5 mg/kg bw colistin sulfate for 1, 3 or 7 days successively. To assess the recoverability of colistin-induced neurotoxicity, the neurotoxicity was also examined on day 15 (8 post colistin sulfate administration for 7 days). The results showed that, the spontaneous activities of mice were significantly decreased on days 3 and 7 in the 15 mg/kg group compared with the correspondingly control group. The abnormal ultrastructure changes of mitochondria were presented in their nervous tissues and changed in a dose- and time-dependent manner, e.g. severe vacuolation and fission on days 3 and 7 in the 15 mg/kg group and more slight on day 7 in the 7.5 mg/kg group. In addition, mitochondrial permeability transition (MPT), membrane potential (Δψ_m) and activities of mitochondrial succinate dehydrogenase changed, showing that colistin affected the mitochondrial functions. The recoverability of colistin-induced neurotoxicity was showed and only slight injury occurred in the nerve tissues of mice on day 15 in the 15 mg/kg group and it had no abnormal changes in the behavioral and neuropathology characters in mice on day 15 in the 7.5 and 5 mg/kg groups. The results suggested that mitochondrial dysfunction might partly account for the mechanism of neurotoxicity induced by colistin sulfate.     

Application of a time-resolved fluoroimmunoassay for detection of p16INK4a in cervix

Objective: To establish a time-resolved fluoroimmunoassay (TRFIA) method to detect p16INK4a. Methods: 119 cases of exfoliative cells following Thinprep cytologic test (TCT) test were selected for TRFIA and biopsy tissues of these patients according to TCT results were collected for immunohistochemical (IHC) staining. Results: There were 40 cases with cervicitis, 16 cases of cervical intraepithelial neoplasia grade 1 (CIN1), 15 cases of CIN2, 26 cases of CIN3, and 22 cases of squamous cell carcinoma (SCC). For each group, TCT results displaying above ASC-US were 7, 6, 12, 23, and 21 cases. IHC results were positive for 2, 13, 14, 26, and 21 cases, while the TRFIA results were positive for 5, 12, 13, 25, and 21 cases, respectively. The sensitivity and specificity were not significantly different between TCT and TRFIA test due to the limited cases. Significantly more CIN1 cases were positive by TRFIA, as compared with cervicitis (75.00% vs. 12.50%, χ² = 21.116, p < 0.001). Most (93.65%) CIN2/3 and SCC cases were positive for p16INK4a (higher than CIN1, χ² = 4.877 and p = 0.027). Conclusion: Detecting p16INK4a protein by TRFIA is suitable to discriminate cervical dysplastic/neoplastic lesions from cervicitis. A commercial kit which created in the future might be a rapid, simple, and low-cost method to obtain objective results with an instrument automatically on a large scale.     

Characterisation and functional implications of the two new HLA-G alleles found in Amerindian and Caribbean populations

HLA-G polymorphism has been found to be relatively low in all world populations. In the present paper two new HLA-G molecules are described in ancient American natives. A new HLA-G molecule from a Ecuador Amerindian individual (male) showed four codon changes with respect to HLA-G*01:01:01. Silent changes at α1 domain (residue 57, Pro, CCG → CCA) and α2 domain (residue 93, His, CAC → CAT and residue 100, Gly, GGC → GGT) and one productive change in α3 domain (residue 219 changed from Arg to Trp). This α3 change may dramatically alter HLA-G interactions with beta-2 microglobulin, CD8, ILT-2 and ILT-4 ligands present in subsets of T, B, NK, monocytes, macrophages and dentritic cells. Another HLA-G new molecule was found in a woman from Hispaniola Island, Dominican Republic (Sto Domingo): it presented a silent change at α2 domain residue 107, Gly, GGA → GGT and non-silent change at residue 178, Met → Thr (with respect to HLA-G*01:01:01) which is close to class I molecule/clonotypic T cell receptor interaction sites. Functional implications of these findings are discussed.     

Direct comparison of two vaginal self-sampling devices for the detection of human papillomavirus infections

Background and objectivesTwo devices for vaginal self-sampling of dry cell material (Evalyn Brush, Rovers Medical Devices; Qvintip, Aprovix) were compared using the Abbott RealTime High Risk HPV test.Study designBoth self-sampling devices (change of order with every patient) including instructions for use and a questionnaire were handed to 146 patients in a colposcopy clinic prior to scheduled colposcopies with collection of cervical reference specimens by gynaecologists using a broom-like device. Matched self-collected and physician collected specimens were transferred to ThinPrep medium and tested for the presence of hr-HPV. Biopsies were taken if indicated by colposcopy.ResultsEvaluation of 136 patients with complete data (136/146; 93.2%) showed high agreement of overall hr-HPV detection rates between self-collected and clinician-collected specimens (Evalyn: 91.2% [kappa 0.822]; Qvintip: 89.0% [kappa 0.779]). Colposcopy and histological evaluation revealed 55 women without cervical intraepithelial neoplasia (CIN), 32 CIN1, 34 CIN2, 14 CIN3 and one adenocarcinoma in situ. Hr-HPV testing detected all CIN3+ cases on the clinician-taken or Evalyn self-samples (14/14) and 93% of them on the Qvintip samples (13/14). There was no significant difference regarding the sensitivity for CIN2+ or CIN3+ and specificity of hr-HPV testing on self- vs. clinician samples and on Evalyn vs. Qvintip. Based on signal intensities of β-globin, the observed DNA concentration with Evalyn samples (mean CN: 22.0; 95%-CI: 21.5–22.6) was found to be significantly higher compared to that of Qvintip samples (mean CN: 23.8; 95%-CI 23.2–24.4), regardless of the order of self-sampling (p < 0.0001). Most women considered self-sampling easy and comfortable. Qvintip was considered easier than the Evalyn Brush to understand (p < 0.001) and to use (p = 0.002).DiscussionThis study confirms that hr-HPV testing with a clinically validated PCR-based HPV assay is as accurate on self-samples as on clinician-samples without significant difference between both self-sampling devices.     

Clinico-hematological and micronuclear changes induced by cypermethrin in broiler chicks: Their attenuation with vitamin E and selenium

This study was carried out on 90 one-day-old broiler chicks to know clinico-hematological alterations, DNA damage caused by cypermethrin (CY), and attenuation of toxic effects by vitamin E (Vit E) and selenium (Se). Birds were randomly divided into five equal groups. Groups 1–4 received CY (600 ml kg^?1 b.wt) daily for 30 days by crop tubing. In addition to CY, groups 2, 3 and 4 received Vit E (150 mg kg^?1 b.wt), Se (0.25 mg kg^?1 b.wt), and Vit E (150 mg kg^?1 b.wt)+Se (0.25 mg kg^?1 b.wt), respectively. Group 5 served as control. Birds were monitored twice daily for clinical signs. They were weighed and blood samples were collected at experimental days 10, 20 and 30 for hematological studies. CY-treated birds showed more prominent signs of toxicity compared to CY+Vit E, CY+Se and CY+Vit E+Se birds. Body weight in groups 1–3 was significantly (P<0.05) smaller at days 20 and 30 when compared with the control group. Significantly (P<0.001) higher numbers of micronuclei appeared in chicks treated with CY compared to CY+Vit E- and CY+Se-treated birds. Significantly decreased total erythrocyte counts (TEC), hemoglobin (Hb) concentration and packed cell volume (PCV) in all treated groups were recorded. Treated birds suffered from macrocytic hypochromic anemia. Leukocytosis in early stage and later leucopenia was seen in treated birds. It can be concluded that CY induces toxic effects in broilers chicks; however, these toxic effects can be ameliorated by Vit E or Se. Combination of Vit E and Se was more effective to ameliorate toxic effects of cypermethrin.     

The effect of rosmarinic acid on 1,2-dimethylhydrazine induced colon carcinogenesis

This study was carried out to investigate the chemopreventive potential of rosmarinic acid (RA) against 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the effect of RA on tumour formation, antioxidant enzymes, cytochrome P450 content, p-nitrophenol hydroxylase and GST activities. Rats were divided into six groups and fed modified pellet diet for the entire experimental period. Group 1 served as control, group 2 received RA (10 mg/kg b.w.). Groups 3–6 were induced colon cancer by injecting DMH (20 mg/kg b.w.) subcutaneously once a week for the first four weeks (groups 3–6). In addition, RA was administered at the doses of 2.5, 5 and 10 mg/kg b.w. to groups 4–6 respectively. DMH treated rats showed large number of colonic tumours; decreased lipid peroxidation; decreased antioxidant status; elevated CYP450 content and PNPH activities; and decreased GST activity in the liver and colon. Supplementation with RA (5 mg kg/b.w.) to DMH treated rats significantly decreased the number of polyps (50%); reversed the markers of oxidative stress (21.0%); antioxidant status (38.55%); CYP450 content (29.41%); and PNPH activities (21.9%). RA at the dose of 5 mg/kg b.w. showed a most pronounced effect and could be used as a possible chemopreventive agent against colon cancer.     

Association between high risk human papillomavirus infection and co-infection with Candida spp. and Trichomonas vaginalis in women with cervical premalignant and malignant lesions

BackgroundHuman papillomavirus (HPV) is the necessary cause of cervical cancer. Cervico-vaginal infection with pathogens like Chlamydia is a likely cofactor. The interactions between HPV, Trichomonas vaginalis (TV) and Candida spp. are less understood, though inflammation induced by these pathogens has been demonstrated to facilitate oncogenesis.ObjectiveOur study aimed to evaluate the association between Candida spp. and TV co-infection with HPV in cervical oncogenesis.Study designWomen with normal cervix who were high-risk HPV-negative (N = 104) and HPV-positive (N = 105); women with CIN 1 (N = 106) and CIN 2/CIN 3 (N = 62) were recruited from a community based cervical cancer screening program. Cervical cancer patients (N = 106) were recruited from a tertiary care oncology clinic. High-risk HPV was detected by Hybrid Capture II technique; Candida spp. and TV were detected by culturing the high vaginal swabs followed by microscopic examination in all. The disease status was established by histopathology in all the women.ResultHPV-positive women had significantly higher risk of having precursor lesions (of any grade) and cancer compared to HPV-negative women. Candida spp. or TV infection did not alter the risk of low grade or high grade lesions among HPV- positive women. HPV positive women co-infected with TV had higher risk of cervical cancer but not those co-infected with Candida spp.ConclusionThe higher risk of cancer observed in the women co-infected with HPV and TV without any enhanced risk of CIN 3 suggests secondary infection of the malignant growth by TV rather than any causal role. Co-infection with Candida spp. and/or TV infection did not increase the carcinogenic effect of HPV on cervix.     

Preventive effect of a galactoglucomannan (GGM) from Dendrobium huoshanense on selenium-induced liver injury and fibrosis in rats

This study was carried out to investigate the preventive effects of galactoglucomannan (GGM), a homogeneous polysaccharide from Dendrobium huoshanense, on liver injury and fibrosis induced by sodium selenite. Sprague–Dawley rats injected subcutaneously with sodium selenite at the dosage of 3.28 mg kg^?1 b. wt. were set as the model groups. Rats treated with sodium selenite at the dosage of 3.28 mg kg^?1 b. wt. and GGM at 50–200 mg kg^?1 b. wt. were set as the prevention groups. Biochemical and histological analysis showed that GGM significantly ameliorated selenite-induced liver injury and fibrosis in rats. Oral administration of GGM effectively attenuated the toxicity of selenite to liver tissue, which was judged both by the decreased activities of serum hepatic enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), and by liver histopathological examination. Meanwhile, GGM also reduced the levels of H₂O₂ and malondialdehyde (MDA), elevated the levels of GSH, restored the fluidity of hepatic plasma membrane, and retained the activities of endogenous enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST). The prevention of selenite-induced liver injury and fibrosis by GGM was further supported by the reduced expression of transforming growth factor-β1 (TGF-β1) and type I collagen. These results suggested that GGM may be developed into a novel antifibrotic agent for the prevention of liver injury and fibrosis.     

Effect of different doses of hexavalent chromium on mandibular growth and tooth eruption in juvenile Wistar rats

Not only workers employed at industrial plants are exposed to intoxication with the element they manipulate, the population at large is also at risk of suffering health problems caused by contaminating wastes inadequately treated for their safe disposal. As a result certain toxic substances, such as hexavalent chromium,has reached the general population including children. The present study sought to evaluate the effect of intoxication with hexavalent chromium on body and mandibular growth and tooth eruption in suckling Wistar rats. Potassium dichromate was administered by gavage in a dose of 6.25 or 12.5 mg/kg body weight (b.w.) to one of the two groups of 4-day-old Wistar rats during 10 days. Our results showed that the effects of chromium are dose-dependent. Morphometric studies of body growth showed lower body weight in both experimental groups and shorter tail length in animals receiving 12.5 mg/kg b.w. dose of chromium, compared with controls. All parameters of mandibular growth were lower in the experimental group receiving 12.5 mg/kg b.w. of chromium. Differences in tooth eruption were observed at the level of the first molar in animals receiving 12.5 mg/kg and of the second molar in those receiving 6.25 mg/kg b.w. of chromium. Chromium was found to affect all the studied parameters.     

Cardiac and renal distribution of ACE and ACE-2 in rats with heart failure

Congestive heart failure is often associated with impaired kidney function. Over-activation of the renin–angiotensin–aldosterone system (RAAS) contributes to avid salt and water retention in heart failure. While the expression of angiotensin converting enzyme (ACE), a key enzyme in the synthesis of angiotensin II (Ang II), is well established, the expression of angiotensin converting enzyme-2 (ACE-2), an enzyme responsible for angiotensin 1–7 generation, is largely unknown. This issue is of a special interest since angiotensin 1–7 counteracts many of the proliferative and hypertensive effects of angiotensin II. Therefore, the present study was designed to investigate the expression of both enzymes in the kidney and heart of rats with heart failure. Heart failure (CHF) was induced in male Sprague Dawley rats (n = 9) by the creation of a surgical aorto-caval fistula. Sham-operated rats served as controls (n = 8). Two weeks after surgery, the animals were sacrificed and their hearts and kidneys were harvested for assessment of cardiac remodeling and ACE and ACE-2 immunoreactivity by immunohistochemical staining. ACE immunostaining was significantly increased in the kidneys (4.34 ± 0.39% vs. 2.96 ± 0.40%, P < 0.05) and hearts (4.57 ± 0.54% vs. 2.19 ± 0.37%, P < 0.01) of CHF rats as compared with their sham controls. In a similar manner, ACE-2 immunoreactivity was also elevated in the kidneys (4.65 ± 1.17% vs. 1.75 ± 0.29%, P < 0.05) and hearts (5.48 ± 1.11% vs. 1.13 ± 0.26%, P < 0.01) of CHF rats as compared with their healthy controls. This study showed that both ACE and ACE-2 are overexpressed in the cardiac and renal tissues of animals with heart failure as compared with their sham controls. The increased expression of the beneficial ACE-2 in heart failure may serve as a compensatory response to the over-activity of the deleterious isoform, namely, angiotensin converting enzyme 1(ACE-1).