Effect of pravastatin on cisplatin-induced nephrotoxicity in rats

2010 ◽  
Vol 30 (7) ◽  
pp. 603-615 ◽  
Author(s):  
Mikiya Fujieda ◽  
Taku Morita ◽  
Keishi Naruse ◽  
Yoshihiro Hayashi ◽  
Masayuki Ishihara ◽  
...  

We investigated whether pravastatin ameliorates renal damage induced by cisplatin (CP). Forty-three male Wistar rats were divided into four groups: rats treated with a control diet for 19 days and saline injection on day 14 (group1), group 1 with pravastatin treatment with 19 days (group 2), group 1 with CP injection on day 14 (group 3), and group 2 with CP injection (group 4). Renal function and serum lipids, renal malondialdehyde (MDA) and glutathione (GSH) levels, glutathione peroxidase (GPx) mRNA expression and activity, and kidney triglyceride (TG) concentrations were measured. Histology was evaluated by light microscopy with immunohistochemistry for p53, p53-upregulated modulation of apoptosis (PUMA), and terminal deoxynucleotide transferase dUTP nick end-labeling (TUNEL) staining. CP induced renal tubular damage with a higher MDA level, increased PUMA expression, p53- and TUNEL-positive cells counts, elevation of serum lipids, and decreased GSH level, GPx mRNA expression, and activity. Pravastatin partially ameliorated CP-induced renal injury, based on suppression of the renal MDA and TG levels, decreased p53 expression, and apoptosis in CP-treated rats. These findings suggest that pravastatin has a partial protective effect against CP nephrotoxicity via antioxidant activity as well as attenuation of the p53 response, and lipid-lowering effects.

2017 ◽  
Vol 181 (5) ◽  
pp. 118-118 ◽  
Author(s):  
I. Wagner ◽  
K. J. Geh ◽  
M. Hubert ◽  
G. Winter ◽  
K. Weber ◽  
...  

Cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN) are a promising new immunotherapeutic treatment option for canine atopic dermatitis (AD). The aim of this uncontrolled pilot study was to evaluate clinical and immunological effects of gelatine nanoparticle (GNP)-bound CpG ODN (CpG GNP) on atopic dogs. Eighteen dogs with AD were treated for 8 weeks (group 1, n=8) or 18 weeks (group 2, n=10). Before inclusion and after 2 weeks, 4 weeks, 6 weeks (group 1+2), 8 weeks, 12 weeks and 16 weeks (group 2) 75 µg CpG ODN/dog (bound to 1.5 mg GNP) were injected subcutaneously. Pruritus was evaluated daily by the owner. Lesions were evaluated and serum concentrations and mRNA expressions of interferon-γ, tumour necrosis factor-α, transforming growth factor-β, interleukin (IL) 10 and IL-4 (only mRNA expression) were determined at inclusion and after 8 weeks (group 1+2) and 18 weeks (group 2). Lesions and pruritus improved significantly from baseline to week 8. Mean improvements from baseline to week 18 were 23 per cent and 44 per cent for lesions and pruritus, respectively, an improvement of ≥50 per cent was seen in six out of nine and three out of six dogs, respectively. IL-4 mRNA expression decreased significantly. The results of this study show a clinical improvement of canine AD with CpG GNP comparable to allergen immunotherapy. Controlled studies are needed to confirm these findings.


2012 ◽  
Vol 11 (2) ◽  
pp. 60
Author(s):  
Shereen K. K.

Forty, one-day-old male broiler chicks (Ross 308), were randomly distributed at one day of age to 2 experimental groups consisting of 10 birds with two replicates for 35 days. Group 1 fed control diet with no T-2 toxin (negative control),while group 2 fed T-2 toxin contaminated diet at a rate of 4 ppm. Scarifying birds done at the end of the experiment, bursa of Fabricius, spleen, liver, kidney and intestine, were sectioned for microscopical examination . Results showed that T-2 toxin, was hepatotoxic, nephrotoxic, toxic to lymphatic tissue, haemopoetic tissue, and gastrointestinal tissues. And these organs are considered to be the target organs for T-2 toxin which primarily affected during T-2 toxicosis.


2020 ◽  
Vol 3 (1) ◽  
pp. 1-3
Author(s):  
Vachan Mehta ◽  
Darshak Salat

Background: Cigarette smoking leads to increased serum level of total cholesterol, LDL cholesterol, Triglyceride levels and decreased level of anti atherogenic HDL cholesterol. Many studies have shown a dose-dependent relationship between smoking and lipoprotein profile. Hence this study was-taken up to know the lipoprotein pattern in healthy young smokers. Subjects and Methods: Total of hundered healthy smokers and fifty healthy non smokers were included in the study. All the smokers’ subjects were divided in two groups as per the severity of the habit of smoking. Group 1: all those who smoke upto 10 cigarette per day, Group 2: all those who smokemore than 10 cigarette per day. Results: In our study, the mean serum cholesterol of smokers is 205.9 26.1 and that of non-smokers is 165.4 15.2 which is statistically significant Mean HDL-cholesterol is 34.20 4.0 in smokers and 38.40 6.4 in non-smokers, which is statistically significant. Mean LDL-cholesterol is 155.8±29.30 in smokers and 136.70 ±14.45 in nonsmokers which is statistically significant. Mean Triglyceride level in smokers is 163.28±38.7  and in non-smokers it is 116.72±23.3 which is statistically significant. Conclusion: The mean serum lipid values were significantly higher in smokers except HDL-C which were significantly decreased, as compared to non smokers. There is a linear increase in the levels of serum lipids except HDL-C which shows decrease in the levels with the duration and severity of smoking.


Author(s):  
AA Rogozhina ◽  
AV Alessenko ◽  
IN Kurochkin ◽  
LO Minushkina ◽  
UA Gutner ◽  
...  

Lipid-lowering drugs affect standard lipoproteins. However, we have no knowledge of changes in other plasma lipids upon treatment. The study was aimed to assess the dynamic changes in cholesterol, high- and low-density lipoproteins (HDL and LDL), triglycerides, and sphingolipids against the background of lipidlowering therapy in patients with premature coronary artery disease, atherosclerosis and hypercholesterolemia. A total of 18 patients were enrolled (the average age was 53 ± 6.7 years): in group 1, six patients received starting statin doses; group 2 included six patients, who failed to achieve LDL target levels against the background of treatment with starting statin doses, and received escalated statin doses; seven patients in group 3 failed to achieve LDL target levels against the background of treatment with maximum tolerated doses of statins and ezetimibe, and received alirocumab. Sphingolipid levels were assessed by mass spectrometry. In group 1, the decreased levels of ceramide Cer 14:1 (p = 0.046) and sphingomyelins SM 22:1, SM 22:0, SM 24:0 (p = 0.028) were observed. There were no significant changes in the levels of total cholesterol, LDL-C, HDL-C, and triglycerides. In group 2, the significantly decreased levels of total cholesterol (p = 0.028), LDL (p = 0.043), sphingomyelins SM 18:1, SM 24:1 and SM 26:1, and ceramide Cer 16:1 (p = 0.028) were observed. The level of Cer 22:1 significantly increased (p = 0.028). In group 3, total cholesterol decreased by 36.2%, and LDL-C (p = 0.018) decreased by 60.1% compared to baseline (ΔLDL-C = –2.67 ± 3.12); the elevated levels of ceramide Cer 22:1 (p = 0.028) were observed. It has been shown, that decreased sphingomyelin levels are associated with statin therapy and correlate with decreased levels of LDL-C. No significant dynamic changes in ceramides and ceramide risk against the background of statin therapy were observed, however, PCSK9 inhibitor added to therapy reduced the Cer 16:0/24:0 ratio.


Author(s):  
Zuhal Yetkin Ay ◽  
Burcu Bakır ◽  
Şerife Buket Bozkurt ◽  
Seyit Ali Kayis ◽  
Sema Sezgin Hakki

Abstract. This study examined the effect of curcumin on T-helper (Th17) and T-regulatory (Treg) cells regarding the mRNA of cytokines/mediators in the gingiva. Thirty-five male albino Wistar rats were divided into four groups: Group 1: periodontitis (n = 9); Group 2: periodontitis with curcumin treatment (n = 8); Group 3: periodontally healthy with curcumin treatment (n = 10); and Group 4: periodontally healthy (n = 8). Curcumin was administered via oral gavage (30 mg/kg/day) for a total of 15 days. The gingival tissues were investigated regarding mRNA expressions of Th17/Treg cytokines with qRT-PCR. The distributional properties of the data were evaluated using the Anderson-Darling normality test. Kruskal-Wallis and Mann-Whitney U tests were employed for multiple group comparisons. Partial least squares regression discriminant analysis (PLS-DA) was used to evaluate the degree of contribution of each mRNA to the separation of treatment groups. When the periodontitis groups were compared, curcumin treatment resulted in lower IL-1β (Group 2 median: 0.002, Group 1 median: 0.12) and IL-6 (Group 2 median: 0.031, Group 1 median: 0.078) and higher IL-17 (Group 2 median: 1.07, Group 1 median: 0.583) relative mRNA expression in Group 2 than in Group 1 (p < 0.001). Group 3 also had higher IL-10 relative expression (median: 0.067) than Groups 1 and 4 (median: 0.028, 0.007, respectively. p < 0.001). These results indicate that curcumin might be a promising agent for the prevention and/or treatment of periodontal diseases due to its decreasing effect on IL-1β and IL-6 mRNA expression.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T.V Fofanova ◽  
M.D Smirnova ◽  
F.T Ageev

Abstract Background Long-term adherence to lipid-lowering treatment is a challenge. Purpose To develop a technical tool, an auto-call program, aimed to increase patient adherence to lipid-lowering therapy, and patient outcome in ambulatory care. Methods 919 ambulatory patients were studied, divided to three groups: with low or moderate risk of developing atherosclerosis complications (Group 1); with high or very high risk of atherosclerosis complications, but without coronary artery disease (CAD) symptoms (Group 2); patients with symptomatic CAD (Group 3). At baseline, patients were invited to participate in the auto-call program (call-reminder to take the medication); the duration of study was 1 year. 663 patients (71.3%) consented to auto-calls received, 256 patients (28.7%) declined auto-calls. These two groups were comparable according to age, gender, the presence of comorbidities, the level of baseline adherence to lipid-lowering therapy, and the level of anxiety and depression. Treatment adherence was evaluated using Morisky-Green Medication Adherence Scale. Results Group 1. After 1 year, the auto-call group showed a significantly higher degree of decrease in low-density lipoprotein cholesterol, LDL-C (p=0.001) and triglyceride, TG (p=0.002), and increase in high-density lipoprotein cholesterol, HDL-C (p=0.03) compared to the auto-call rejection group. Group 2. After 1 year, the auto-call group showed a significantly higher degree of decrease in total cholesterol, TC (p&lt;0.02) and LDL-C (p&lt;0.01), and increase in HDL-C (p=0.2) compared to the auto-call rejection group. Moreover, in the auto-call group, the baseline TC level was higher (6.4±1.5 mmol/l vs 6.0±1.4 mmol/l, p=0.03). Group 3. After 1 year, the auto-call group showed a significantly higher degree of decrease in TC (p&lt;0.005) and TG (p&lt;0.05). The degree of decline in LDL-C was higher in the auto-call group (−25.9 (−27.3; −17.0) vs −20.1 (−21.3; −0.2), however, non-significant. After 1 year, treatment adherence increased in the total cohort from 1.91 score (1.80; 2.02) to 2.6 score (2.52; 2.80), p&lt;0.000001. However, in Group 3, a significant increase in scores from 2.0 (1.9; 2.2) to 3.0 (2.6; 3.1) was observed only in the auto-call group (p&lt;0.00001). In Group 1 and Group 2, the increase in adherence did not depend on the presence or absence of auto-calls. It should be noted that adherence to therapy in patients of Group 3 was significantly higher at baseline (2.0 (1.9; 2.2) than in Group 1 (1.7 (1.6; 1.9), p&lt;0.005) and Group 2 (1.9 (1.7; 2.1), p&lt;0.05), respectively. Conclusions Utilizing a high-tech auto-call reminder tool in patients with hyperlipidemia and CAD was associated with increased adherence to lipid-lowering therapy, which, in turn, resulted in significant decrease in LDL-C compared to patients who declined to participate in the auto-call program. Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 888 (1) ◽  
pp. 012033
Author(s):  
M Z Sukiman ◽  
M H Chai ◽  
N S Sharifuddin ◽  
A Shamin ◽  
S M Z Ariffin ◽  
...  

Abstract Mastitis is a common disease in small ruminant industry. The present study aimed to determine the presence of protease activated receptor-2 (PAR2) mRNA expression in the mammary gland of mastitis challenged goats. 30 clinically healthy mix breed lactating goats were divided into three groups, consisting of Staphylococcus aureus (Group 1), methicillin-resistant S. aureus (Group 2) and sterile phosphate-buffered saline (Control) groups. The data regarding physical condition of udder and clinical parameters of goats were recorded while milk samples and mammary gland tissues were collected at 24 and 48 hours post infection. Somatic cell count (SCC) was measured by direct microscopic method. The presence of PAR2 mRNA in the mammary gland tissue samples was detected by real-time PCR. Goats from group 1 developed mild to moderate clinical signs while Group 2 exhibited moderate to severe clinical signs. SCC was higher in both challenged groups than control group. PAR2 mRNA expression was detected in all mammary gland samples from Group 1 and Group 2. The gene expression was significantly highly in mammary gland tissue with severe clinical signs. The finding of PAR2 expression in caprine mammary gland is novel and important, suggesting serine proteases involved the development of mastitis in goat.


2010 ◽  
Vol 22 (9) ◽  
pp. 41
Author(s):  
H. W. Bakos ◽  
N. O. Palmer ◽  
M. Lane

While the effects of obesity on male fertility are emerging, the direct effects on sperm function are less clear. The aim of this study was to determine the effects of diet-induced obesity on sperm capacitation, acrosome reaction, oocyte binding and fertilisation. C57/Bl6 male mice (n = 12) were randomly allocated to two groups; group 1 received a control diet (6% fat) while group 2 received a high fat diet (HFD, 22% fat) for up to 14 weeks. Mice were sacrificed and spermatozoa obtained. Capacitation and acrosome reaction were measured using Arachis hypogaea (peanut) agglutinin. Sperm binding to oocytes was assessed by co-incubation of sperm with superovulated cumulus-enclosed oocytes for 4 hrs. Fertilisation rates were expressed as the percentage of oocytes with 2 pronuclei from the total number inseminated 6 hrs post insemination. The percentage of non-capacitated sperm in males fed a high fat diet was significantly lower compared to males fed a control diet (12.3% vs 21.1%; P < 0.01). The percentage of acrosome reacted sperm did not differ between the groups. Following 4 hrs of co-incubation with cumulus-enclosed oocytes, the number of sperm bound to each oocyte was significantly lower in the HFD group compared to controls (41.14±2.5 vs 58.39±2.4; P < 0.01). Moreover, the percentage of fertilized oocytes was significantly lower in the HFD group compared to controls (25.9% vs 43.9; P < 0.01). This study demonstrates that males fed a HFD to induce obesity have impaired spermatozoa as evidenced by lower levels of capacitation and reduced ability to bind and fertilise an oocyte. These data therefore provide direct evidence that the metabolic health of the male can have a significant impact on sperm function parameters that are associated with infertility.


2020 ◽  
Vol 15 ◽  
Author(s):  
Naci Senkal ◽  
Ozum Atasoy ◽  
Emine Bilge Caparali ◽  
Mumin Alper Erdogan ◽  
Oytun Erbas

Background:: Colistin utilization has gradually increased worldwide with the arising of multidrug-resistant (MDR) gram-negative bacilli despite its nephrotoxicity. Lipid emulsion (LE) is widely used for the toxic overdose treatment of various drugs. Objective:: The aim of the present study is to evaluate the effect of lipid emulsion on improvement of renal damage in colistin-induced nephrotoxicity with experimental Sprague Dawley rat model. Methods:: Twenty-four male Sprague Dawley rats were initially assigned at random into 2 groups. Sixteen rats were given a single dose of 20 mg/kg colistin, eight rats received no medication (control group). Sixteen rats that were administered colistin sub-divided into 2 groups. Group 1/LE rats (n = 8) were given 20 ml/kg solution of lipid emulsion, and group 2/S rats (n = 8) were given 20 ml/kg/day (i.p.) of 0.9% NaCl saline; both were administered for 10 days. Then tubular injury was evaluated histopathologically. Serum levels of blood urea nitrogen (BUN), Kidney Injury Molecule-1 (KIM-1), and creatinine were measured. Besides, malondialdehyde (MDA) levels were determined in tissue samples for the assessment of lipid peroxidation. Results:: The mean percent of tubular epithelial cell injury and tubular dilatation was found significantly higher in group 2/S than control and group 1/LE (p < 0.0001 and < 0.001; respectively). KIM-1 and MDA levels were also statistically higher in group 2/S than control and group 1/LE. (p < 0.0001 and < 0.0001; respectively). Additionally, serum BUN and creatinine levels of group 2/S were significantly greater than control and group 1/LE (p < 0.0001 and < 0.0001; respectively). Conclusion:: In this present study, we determined that colistin-induced proximal tubular damage was decreased as histopathologically and serologically by the effect of lipid emulsion. Thus, our findings may guide to the future studies on the clinical use of colistin., particularly in MDR positive intensive care infections.


1993 ◽  
Vol 85 (5) ◽  
pp. 557-562 ◽  
Author(s):  
M. Yaqoob ◽  
A. W. Patrick ◽  
P. McClelland ◽  
A. Stevenson ◽  
H. Mason ◽  
...  

1. Diabetic nephropathy is a serious microvascular complication in patients with insulin-dependent diabetes mellitus, resulting in end-stage renal disease in 30–45% of such patients. Despite intensive investigation, the pathophysiology of diabetic renal disease has not been fully elucidated. However, several clinical and experimental studies have suggested that endothelial dysfunction and free-radical activity may be important factors. 2. Forty normotensive patients with insulin-dependent diabetes mellitus of between 10 and 20 years duration with persistent normoalbuminuria (albumin excretion <30 mg/day) and normal renal function were investigated for markers of endothelial dysfunction (plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity), free oxygen radical generation (erythrocytic superoxide dismutase and glutathione peroxidase) and oxidant injury (serum malondialdehyde). Glomerular proteinuria (albuminuria, transferrinuria), tubular proteinuria (retinol-binding protein) and tubular enzymuria (N-acetyl glucosaminidase and leucine aminopeptidase) were also measured. 3. Patients were divided into two groups. Group 1 comprised 21 patients with elevated markers of endothelial dysfunction, and group 2 comprised 19 patients with normal levels of plasma von Willebrand factor, soluble thrombomodulin and angiotensin-converting enzyme activity. Thirty-eight healthy subjects matched for age and sex acted as controls. 4. Groups 1 and 2 were similar in age, sex, body weight, duration of diabetes mellitus and recent glycaemic control. Serum cholesterol, serum creatinine and glomerular proteinuria were similar in the three groups. Group 1 patients had significantly increased oxidant injury, tubular enzymuria and proteinuria compared with group 2 patients and control subjects (P <0.01). Erythrocytic glutathione peroxidase was significantly lower in group 1 compared with the other groups (P <0.01) and erythrocytic superoxide dismutase was lower in both diabetic groups compared with normal control subjects (P <0.01). Serum malondialdehyde, tubular enzymuria and proteinuria were comparable in group 2 patients with control subjects. 5. We conclude that endothelial dysfunction, oxidant injury and renal tubular damage may precede microalbuminuria in diabetic nephropathy. These data support the hypothesis that endothelial dysfunction first affects the postglomerular microvessels. It is associated with oxidant injury and renal tubular damage, which may be factors in the initiation of diabetic nephropathy.


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