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Renal Effects
Published in Lars Friberg, Tord Kjellström, Carl-Gustaf Elinder, Gunnar F. Nordberg, Cadmium and Health: A Toxicological and Epidemiological Appraisal, 2019
Metallothionein thus acts as a sequestering agent for cadmium in plasma. Various chelating agents have been investigated as to their ability to increase urinary excretion or reduce cadmium damage to several organs (Chapter 6, Section VII.B). Ethylene-diamine-tetraacetic acid (EDTA) and diethylene-triamine-pentaacetic acid (DTPA) have been reported to decrease the renal uptake of cadmium,61,70 whereas 2,3-dimercapto-propanol (BAL) increased the uptake of cadmium in the kidneys.150,248 The nephrotoxicity of cadmium was increased by combined BAL and cadmium exposure.46
The Effects of Tin Compounds on Cell Growth and Development*
Published in Nate F. Cardarelli, Tin as a Vital Nutrient:, 2019
John S. Thayer, R. B. Jonas, J. J. Cooney
Our observations and those of Blair et al.13 suggest that at least some sediment microorganisms use passive adsorption onto the cell envelope as a defense mechanism against poisoning by alkyltin compounds. This adsorption does not apparently involve active metabolism, and there is no evidence for tin-carbon bond cleavage. The increased toxicity of tin compounds in the presence of certain chelating agents is consistent with this mechanism.9 A chelating agent bonding to tin blocks a coordination site that might otherwise bind to some sequestering agent. This might ease passage across the cell membrane and also movement within the cell. In this context, it might be noted that complexes of diorganotin dihalides show antitumor activity,14 and that activity of five-coordinate triorganotin compounds on rat liver mitochondria differed markedly from activity of corresponding four-coordinate compounds.15
The Special Position of 99mTc in Nuclear Medicine
Published in Frank Helus, Lelio G. Colombetti, Radionuclides Production, 2019
Other workers42,43 have suggested that Al-contamination affects the quality of certain radiopharmaceuticals prepared from generator eluates and have recommended the use of a sequestering agent, such as EDTA, to overcome the problem of inconsistent quality. Craigin et al.44,45 found Al-contamination levels in generator eluates ranging from nil to 40 μg/mℓ but could prove no correlation between aluminum content and the clinical performance of batches of 99mTc-sulfur colloid made from the eluates. Chaudhuri 46,47 reported an altered biological distribution of 99mTc-disphosphonate prepared in the presence of 50 |xg aluminum ions. More recently Shukla et al.48 have suggested that the presence of as little as 4 μg/mℓ aluminum ions changes the pertechnetate species to a ‘pertechnetatoaluminum’ complex. These investigators provided evidence of altered chromatography and biodistribution of the pertechnetate species in the presence of aluminum ions.
Aflatoxin M1 in milk and dairy products: global occurrence and potential decontamination strategies
Published in Toxin Reviews, 2022
Khurram Muaz, Muhammad Riaz, Carlos Augusto Fernandes de Oliveira, Saeed Akhtar, Shinawar Waseem Ali, Habibullah Nadeem, Sungkwon Park, Balamuralikrishnan Balasubramanian
The addition of smectite in human nutrition was another initiative in order to decontaminate contaminants (Afriyie-Gyawu et al. 2008a). The efficacy of a specific smectite as a sequestering agent for aflatoxins was observed along with its safety for humans after ingestion (Wang et al. 2005, Afriyie-Gyawu et al. 2008b). The treatments for decontamination of AFM1 involving adsorption may fulfill few of the criterions required for the purpose as these are economical, eliminate the probability for formation of secondary toxic compounds and have been observed to bear high removal efficiencies. Clays were utilized for attenuation of AFM1 in bovine milk by Carraro et al. (2014) who showed bentonites to be highly efficient as the milk contaminated with AFM1 at levels of approximately up to 0.080µg/L was decontaminated to permissible levels with only minute changes in the nutritional profile of milk. Kaolin, however, was found to be less adsorptive than bentonite. High adsorbent capacities were observed by bentonites owing to higher cell surface areas available for AFM1 binding and surface hydrophobicity (Carraro et al. 2014). Additionally, Di Natale and his team observed activated carbons to have higher adsorbing capacities as compared to montmorillonitic bentonite and zeolite which might have been due to larger surface areas of activated carbon in comparison to bentonite (Di Natale et al. 2009). Some recent studies involving use of various adsorbents are shown in Table 4.
Effects of the total flavonoid extracts and the monomers of Daphne genkwa on CYP2C8 activity
Published in Xenobiotica, 2022
Qiaoyu Hou, Yanzhi Liu, Xueting Xing, Shuo Li, Jiaqi Li, Wen Qian, Changqing Yang, Hanhan Li
Studies have shown that the combination of drugs may change the absorption of drugs in the body, which may cause the increase or decrease of the concentration of drugs or their metabolites in blood, and then affect the efficacy (Nishimura 2005; He et al. 2014). Muzeeb et al. reported that the bile acid-sequestering agent cholestyramine had a dose-dependent decrease for both rosiglitazone in AUC and Cmax (Muzeeb et al. 2006). In our study, we found that the mean value of AUC(0-t) and AUC(0-∞) in the treatment group were significantly lower than that of the control group (Table 2). Moreover, the Tmax of the treatment group was significantly increased by 287%, and Cmax was significantly decreased by 66.6% compared with the control group (Table 2). These data indicated that TFDG can inhibit the absorption of rosiglitazone in rats. Sodhi, Benet, and Bowman have studied that changes in drug absorption can affect drug Vz/F, CLz/F, and MRTlast, which are not related to the metabolic elimination process (Benet et al. 2019; Sodhi and Benet 2020a, 2020b). Therefore, the changes in Vz/F, CLz/F, and MRTlast in the pharmacokinetic parameters of rosiglitazone cannot be used to judge the effect of TFDG on CYP2C8 activity in vivo. Meanwhile, TFDG also inhibited the absorption of tolbutamide (in Supplementary Table 1). However, the mechanism of TFDG inhibiting the absorption of rosiglitazone and tolbutamide was not clear, which needs to be further studied.
Targeting TLR4-dependent inflammation in post-hemorrhagic brain injury
Published in Expert Opinion on Therapeutic Targets, 2020
Jason K. Karimy, Benjamin C. Reeves, Kristopher T. Kahle
TLR4 has been implicated in animal models of SAH, ICH, and IVH. Moreover, the inflammatory markers downstream of TLR4 have been consistently reported in humans [26]. The data supporting TLR4 inflammation in multiple etiologies of hemorrhagic stroke make it a strong candidate for targeted therapies and could significantly benefit patients. Yet, despite the progress made in the field there remain many unanswered questions. While many studies demonstrate various components of blood to be TLR4 ligands, there seems to be little consensus on which blood-breakdown products are the most pathogenic in hemorrhagic stroke. Identification and consensus of these pathogenic molecules could provide a target to develop a locally administered sequestering agent to improve prognosis in cases where neurosurgery cannot be avoided. For example, in cases of PHH, neurosurgeons routinely place an extraventricular drain to relieve excess CSF accumulation. This surgery allows direct entry to the ventricular system and could be leveraged to deliver anti-inflammatory drugs to prevent shunt-dependence, delayed vasospasm and microthrombi formation. Until drug therapies can be administered systemically, direct bypass of the BBB, in cases where neurosurgical intervention is the only option, could provide a method to trial novel therapeutics and improve long-term patient outcomes.