Subacute exposure to dimethoate induces hepatotoxic and nephrotoxic effects on male rats: Ameliorative effects of ferulic acid

Dimethoate commonly used as environmental ares for control pests which is widely used throughout in the world and itcaused toxic effects on nontarget organisms especially mammalian. Ferulic acid is known to protective compound generally used in toxicology studies. Thus, inthis study, we investigatedthe protective role of ferulic acid against the possible toxic effects of low and high doses of dimethoate. Male rats were randomly divided into six groups: control; ferulic acid; low and high dose dimethoate; both ferulic acid and low dose dimethoate; both ferulic acid and high dose dimethoate. The dimethoate treatment to rats caused oxidative stress in liver and kidney tissue via increased malondialdehyde levels and changes in superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase activities. All dose dimethoate treatments also caused histopathological alterations and differences in activities in alanine aminotransferase, aspartate aminotransferase, total protein, albumin, lactate dehydrogenase, total cholesterol, urea, uric acid, and creatinine levels. The histopathological results verified the biochemical findings for both liver and kidney. Co-administration of ferulic acid with dimethoate improved antioxidative parameters and eased some biochemical parameters mentioned above. Ferulic acid was also seen to play a beneficial role in the histopathological effects of dimethoate for both liver and kidney

Associations between body mass index across adult life and hip shapes at age 60 to 64:Evidence from the 1946 British birth cohort

Funding: The NSHD is funded by the UK Medical Research Council. SGM, RC, RJH and DK are supported by the UK Medical Research Council (Programme codes: MC_UU_12019/1, MC_UU_12019/2 and MC_UU_12019/4). This project was funded by the UK Medical Research Council (Grant MR/L010399/1) which supported SGM, AVP and FRS. The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of this manuscript. Acknowledgements: We thank Dr. Michael Machin for his valuable assistance obtaining the images and the University of Aberdeen Data Management Team for programming support for ‘Shape’. The authors are grateful to NSHD study members who took part in the clinic data collection for their continuing support. We thank members of the NSHD scientific and data collection teams at the following centres: MRC Unit for Lifelong Health and Ageing; Wellcome Trust (WT) Clinical Research Facility (CRF) Manchester; WTCRF and Medical Physics at the Western General Hospital in Edinburgh; WTCRF and Department of Nuclear Medicine at University Hospital Birmingham; WTCRF and the Department of Nuclear Medicine at University College London Hospital; CRF and the Department of Medical Physics at the University Hospital of Wales; CRF and Twin Research Unit at St Thomas' Hospital London. Data used in this publication are available to bona fide researchers upon request to the NSHD Data Sharing Committee via a standard application procedure. Further details can be found at: http://www.nshd.mrc.ac.uk/data; doi: http://dx.doi.org/10.5522/NSHD/Q102; doi: http://dx.doi.org/10.5522/NSHD/Q102A.Peer reviewedPublisher PD

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Subacute exposure to dimethoate induces hepatotoxic and nephrotoxic effects on male rats: Ameliorative effects of ferulic acid

51-58Dimethoate commonly used as environmental ares for control pests which is widely used throughout in the world and itcaused toxic effects on nontarget organisms especially mammalian. Ferulic acid is known to protective compound generally used in toxicology studies. Thus, inthis study, we investigatedthe protective role of ferulic acid against the possible toxic effects of low and high doses of dimethoate. Male rats were randomly divided into six groups: control; ferulic acid; low and high dose dimethoate; both ferulic acid and low dose dimethoate; both ferulic acid and high dose dimethoate. The dimethoate treatment to rats caused oxidative stress in liver and kidney tissue via increased malondialdehyde levels and changes in superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase activities. All dose dimethoate treatments also caused histopathological alterations and differences in activities in alanine aminotransferase, aspartate aminotransferase, total protein, albumin, lactate dehydrogenase, total cholesterol, urea, uric acid, and creatinine levels. The histopathological results verified the biochemical findings for both liver and kidney. Co-administration of ferulic acid with dimethoate improved antioxidative parameters and eased some biochemical parameters mentioned above. Ferulic acid was also seen to play a beneficial role in the histopathological effects of dimethoate for both liver and kidney

Penicillin-induced oxidative stress: Effects on antioxidative response of midgut tissues in instars of Galleria mellonella

Penicillin and other antibiotics are routinely incorporated in insect culture media. Although culturing insects in the presence of antibiotics is a decades-old practice, antibiotics can exert deleterious influences on insects. In this article, we test the hypothesis that one of the effects of dietary penicillin is to increase oxidative stress on insects. The effects of penicillin on midgut concentrations of the oxidative stress indicator malondialdehyde (MDA) and on midgut antioxidant enzyme (superoxide dismutase [SOD], catalase [CAT], glutathione S-transferase [GST], and glutathione peroxidase [GPx]) and transaminases (alanine aminotransferase and aspartate aminotransferase) activities in greater wax moth, Galleria mellonella (L.), were investigated. The insects were reared from first instars on artificial diets containing 0.001, 0.01, 0.1, or 1.0 g penicillin per 100 g of diets. MDA content was significantly increased in the midgut tissues of each larval instar reared in the presence of high penicillin concentrations. Activities of antioxidant and transaminase enzymes did not show a consistent pattern with respect to penicillin concentrations in diet or age of larvae. Despite the increased penicillin-induced oxidative stress in gut tissue, antioxidant and transaminase enzymes did not correlate with oxidative stress level or between each other in larvae of other age stages except for the seventh instar. We found a significant negative correlation of MDA content with SOD and GST activities in seventh instars. SOD activity was also negatively correlated with CAT activity in seventh instars. These results suggest that exposure to dietary penicillin resulted in impaired enzymatic antioxidant defense capacity and metabolic functions in wax moth larval midgut tissues and that the resulting oxidative stress impacts midgut digestive physiology. © 2007 Entomological Society of America

Galleria mellonella (L.) survivorship, development and protein content in response to dietary antibiotics

Antibiotics are routinely incorporated in insect culture media. Although culturing insects on diets containing antibiotics is a decades-old practice, the antibiotics can exert deleterious effects on the insects. Diets amended with penicillin, streptomycin, fluconazole or griseofulvin were evaluated as to their impact on survivorship, development, wet weight, and adult total protein content of Galleria mellonella (L.). Insects were reared from neonates to adults on artificial diets containing 0.001, 0.01, 0.1 or 1.0 g of the antibiotics (per 100 g diet). Dose- and stage-dependent variations in both biological and biochemical parameters occurred. Penicillin at high concentrations significantly increased the wet weight of the insect, whereas low dietary fluconazole, griseofulvin and streptomycin concentrations significantly increased wet weight and high concentrations decreased wet weight. Dietary antibiotic treatment resulted in significantly decreased survivorship and increased developmental time of larvae. The diet amended with 1.0 g of either penicillin or streptomycin decreased pupation and adult emergence by 50%. Larvae reared on the diets supplemented with the highest concentrations of fluconazole and griseofulvin produced as low as 20% of adults. The 0.1 g fluconazole treatment prolonged adult development by 8 d. High dietary griseofulvin concentrations markedly decreased total protein content of adults. Other antibiotics also resulted in decreased total protein content in adults depending on their types and concentrations. Slightly enhanced survivorship, shortened development and increased total protein content were observed with some sublethal doses of antibiotics. It appears that dietary antibiotic impact on insect biological parameters is exerted via their deteriorative effects on biochemical factors in relation to alterations in wet weight. Low concentrations of these antibiotics can be used in artificial rearing of G. mellonella

Exposure to streptomycin alters oxidative and antioxidative response in larval midgut tissues of Galleria mellonella

Although antibiotics have different molecular modes of actions, increasing evidence for their secondary effects suggests that they disturb cellular homeostasis by generating free radical intermediates that trigger lipid peroxidation, which leads to oxidative stress. Streptomycin is an antibiotic insecticide used to control pest insects and microbial diseases of agricultural crops. We investigated the biochemical basis for pro-oxidative effects of streptomycin in the midgut tissues of greater wax moth, Galleria mellonella (L.) seventh-instar larvae by measuring content of the oxidative stress indicator, malondialdehyde (MDA), and antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and glutathione peroxidase (GPx)] and transaminases [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] activities. The insects were reared from first-instar larvae on artificial diets containing 0.001, 0.01, 0.1 or 1.0 g streptomycin per 100 g of diets. The supplementation of streptomycin at high concentrations to the diets caused oxidative stress as evidenced by the elevation of MDA content, SOD and GPx activities, accompanied by the concurrent depletion of CAT and GST activities. The streptomycin-induced oxidative stress was also accompanied by decreases of transaminases activities in midgut tissues. We found a significant negative correlation of MDA contents with GST activities in the larval midgut tissues. These results suggest that exposure to dietary streptomycin resulted in oxidative stress which could impact midgut digestive physiology at the expense of impairment of antioxidant and transaminases enzymes in G. mellonella larvae. © 2009 Elsevier Inc. All rights reserved