The Toxicity of Aluminum Chloride on Kidney of Rats

Abstract

This study investigated the toxicity of aluminum chloride (AlCl₃) exposure in the rat kidney. Forty male Wistar rats (5 weeks old), weighing 110–120 g, were randomly divided into four groups: control group (CG, 0 g/L AlCl₃), low dose group (LG, 0.4 g/L AlCl₃), mid dose group (MG, 0.8 g/L AlCl₃), and high dose group (HG, 1.6 g/L AlCl₃). Rats were administered AlCl₃ in their drinking water for 120 days. A variety of measurements were taken including superoxide dismutase (SOD) and glutathione peroxidase (GSH-P_X) activities, malondialdehyde (MDA) concentration in the kidney and blood urea nitrogen (BUN), and cystatin C (Cys-C) concentrations in the serum. In addition, Al and β₂-microglobulin (β₂-MG) concentrations and the activity of N-acetyl-β-d-glucosaminidase (NAG) in the urine were determined. The results showed that in the AlCl₃-treated groups SOD and GSH-P_X activities were decreased, while NAG activity and Al, MDA, BUN, Cys-C, and β₂-MG concentrations were increased, compared with the CG. This study indicates that AlCl₃ exposure induces oxidative stress and suppresses kidney function.

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Effects of Corticosterone on Immune Functions of Cultured Rat Splenic Lymphocytes Exposed to Aluminum Trichloride

Abstract

Aluminum (Al) exposure is toxic to immune system. Studies have implicated that glucocorticoids (GCs) exert the dual regulation effect on the immune function depending on the concentration. However, it is unknown whether a dual effect of GCs exists in the AlCl₃-treated lymphocytes. Corticosterone (Cort) is one kind of GCs. To investigate the effect of different concentration Cort on AlCl₃-treated lymphocytes, rat splenic lymphocyte was isolated and cultured with 0.55 mmol/L AlCl₃, simultaneously administrated Cort at final concentration of 0 (control group, CG), 10⁻⁸ (low-level group, LG), and 10⁻⁶ (high-level group, HG) mol/L, respectively. Another group without AlCl₃ and Cort served as the blank group (BG). We found that low concentration Cort increased the T and B lymphocyte proliferation rate, proportions of CD4⁺ T lymphocyte subset, IgG, IL-2, and TNF-α contents, whereas high concentration Cort decreased those in AlCl₃-treated lymphocytes. In conclusion, the results of this study indicated that low concentration Cort relieves the immunotoxicity of AlCl₃ on the splenic lymphocytes, whereas high concentration Cort aggravates it.

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Effects of Dietary Zinc Pectin Oligosaccharides Chelate Supplementation on Growth Performance, Nutrient Digestibility and Tissue Zinc Concentrations of Broilers

Abstract

The experiment was conducted to investigate the effects of zinc pectin oligosaccharides (Zn-POS) chelate on growth performance, nutrient digestibility, and tissue zinc concentrations of Arbor Acre broilers aged from 1 to 42 days. A total of 576 1-day-old broilers were randomly assigned into 4 groups with 9 replicates per group and 16 chicks per replicate. Chicks were fed either a basal diet (control) or basal diet supplemented with Zn-POS at 300 (Zn-POS-300), 600 (Zn-POS-600), or 900 mg/kg (Zn-POS-900), respectively, for 42 days. A 3-day metabolism trial was conducted during the last week of the experiment feeding. The average daily gain and the average daily feed intake of Zn-POS-600 were significantly higher (P < 0.05) than those of either the control, Zn-POS-300, or Zn-POS-900. Zn-POS-600 had the highest apparent digestibility of dry matter, crude protein, and metabolic energy among all groups. The control group had the lowest apparent digestibility of dry matter (P < 0.05), whereas the apparent digestibility of dry matter in Zn-POS-600 was higher (P < 0.05) than that of Zn-POS-300. The apparent digestibility of crude protein in Zn-POS-600 or Zn-POS-900 was higher (P < 0.05) compared to Zn-POS-300 or the control. The apparent digestibility of metabolic energy in Zn-POS-600 or Zn-POS-900 was higher (P < 0.05) than that of Zn-POS-300. Zn-POS-600 had the highest liver zinc concentrations (P < 0.05), while Zn-POS-900 had the highest pancreatic zinc concentrations (P < 0.05). Our data suggest that the supplementation of 600 mg/kg Zn-POS is optimal in improving the average daily gain and the average daily feed intake, utilization of dietary dry matter and crude protein, and increasing tissue zinc concentrations in liver and pancreas of broilers.

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Phase I dose-escalation study of plitidepsin in combination with bevacizumab in patients with refractory solid tumors.

This phase I trial evaluated the toxicity profile and maximum tolerated dose of the combination between the marine derived cyclodepsipeptide plitidepsin and bevacizumab in advanced cancer patients. Thirteen patients were enrolled and treated with plitidepsin at three dose levels (2.8 mg/m2, n=3; 3.8 mg/m2, n=4; and 4.8 mg/m2, n=6) with a fixed dose of bevacizumab (10 mg/kg). Both agents were administered intravenously at D1 and D15 of a 28-day cycle. All 13 patients were evaluable for safety and toxicity. Dose-limiting toxicities occurred in two out of six patients treated at the maximum dose tested (plitidepsin 4.8 mg/m2 and bevacizumab 10 mg/kg) and consisted of grade 3 fatigue, grade 3 myalgia, and two grade 2/3 alanine aminotransferase increases lasting for more than 7 days or leading to subsequent cycle delay greater than 2 weeks (n=1 each). The recommended dose for the combination of plitidepsin with bevacizumab was 3.8 mg/m2 for plitidepsin and 10 mg/kg for bevacizumab every 2 weeks. Most frequent treatment-related adverse events were nausea, vomiting, fatigue, epistaxis, and headache. Relevant hematological toxicity was minimal. Objective disease responses were not observed; however, stable disease (>3 months) was observed in four patients with colorectal cancer, renal cancer, and cervical cancer. Combining plitidepsin with bevacizumab combination is feasible. Stable disease was the best response obtained. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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A randomized double blinded placebo controlled trial of sildenafil for renoprotection prior to hilar clamping in patients undergoing robotic assisted laparoscopic partial nephrectomy

Objective

To perform a randomized control trial (RCT) assessing the effect of phosphodiesterase 5 inhibitor (PDE5i) used prior to hilar clamping during robot assisted partial nephrectomy (RAPN) for renoprotection.

Materials and Methods

We performed an institutional review board approved, placebo controlled, double blinded RCT evaluating a single 100 mg oral dose of sildenafil immediately prior to RAPN. Primary end point was accrual, participation and retention of patients with secondary endpoints assessing post-operative renal functional outcomes and safety. Exclusion criteria included history of coronary artery disease, solitary kidney, suspected benign pathology, PDE5i intolerance or pregnant females.

Results

Of 40 eligible consecutive patients undergoing RPN between 9/2013 and 12/2014, 30 (75%) were randomized to treatment and there was 100% participation and retention. The groups were well matched for all measured comorbidities. Intraoperative outcomes including warm ischemia time (median 15 vs. 16.5 min, P = 0.29) were similar. Change in eGFR demonstrated similar decrease between sildenafil versus placebo at 1 day (−8% vs. −10%, P = 0.53), 2 days (−9% vs. −9%, P = 0.77), and 1 month (−4% vs. −6%, P = 0.31) following RAPN. Intermediate follow up (median 183 days) demonstrated similar results (−8% vs. −1%, P = 0.16) between the two cohorts. Safety profiles were similar between the two cohorts without any adverse reactions to the sildenafil.

Conclusions

Successful retention of patients was achieved in this RCT. The secondary outcome of renoprotection was not identified. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Successful conservative management of diffuse cavernous hemangioma of the rectum

Abstract

Diffuse cavernous hemangioma of the rectum (DCHR) is a relatively rare disease. A 40-year-old man presented with long-standing lower abdominal discomfort and hematuria. At the time of hospitalization, his vital signs and hemoglobin level were normal. Colonoscopy showed markedly dilated blood vessels in the sigmoid mucosa, which was confirmed on magnetic resonance imaging and computed tomography as cavernous hemangioma. Without surgery, there have been no signs of progression of DCHR during a 3-year follow-up period.

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Alkaloid extracts from shea butter and breadfruit as potential inhibitors of monoamine oxidase, cholinesterases, and lipid peroxidation in rats’ brain homogenates: a comparative study

Abstract

Shea butter (Vitellaria paradoxa) and breadfruit (Treculia africana) are wild edible plants commonly consumed across the world. Unfortunately, these plants are currently going into extinction despite their potential biological properties. The actions of alkaloid extract from shea butter nut and breadfruit on some central nervous system biomarkers (monoamine oxidase (MAO), acetylcholinesterase (AChE), butyrylcholinesterase (BChE)) linked to some neurodegenerative diseases were investigated in this study. The radical scavenging and metal chelating abilities of the extract were also studied. Alkaloid extracts were obtained from shea butter and breadfruit via solvent extraction. The total alkaloid content of the extracts and their interactions on MAO, AChE, and BChE were determined. The ability of the extract to inhibit Fe²⁺-induced malondialdehyde (MDA) production in rats' brain homogenates including their radical scavenging and metal chelating abilities were also determined. Breadfruit (17.00 mg CE/g) had higher alkaloid content than shea butter (15.34 mg CE/g). Furthermore, a significant decrease in MAO, AChE, and BChE activities was exhibited by breadfruit compared to shea butter. However, shea butter had stronger antioxidant activity. The observed modulatory effects of the extracts on MAO, AChE, and BChE activities and their antioxidant properties give credence to the fact that they could be a novel multifunctional target for the treatment and management of some neurodegenerative diseases.

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