Decrease in protein binding and its effect on toxicokinetics (TK) / toxicodynamics (TD) of diclofenac and propranolol in pregnant rats

Miida, Hiroaki; Noritake, Yumiko; Shimoda, Hitomi; Honda, Kumi; Matsuoka, Toshifumi; Sakurai, Katsunobu; Shirai, Michio; Manabe, Sunao; Takasaki, Wataru; Ueno, Koichi

doi:10.2131/jts.33.525

Cited by 6 publications

(6 citation statements)

References 13 publications

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“…The genus Cissus has been widely used in traditional herbal medicine for the treatment of hemorrhoids, gastric ulcers and bone healing. Miida et al (2008) after a single administration of diclofenac, on observed the area under plasma concentration-time curve (AUC) based on free diclofenac in pregnant rats was 3.9 times higher than that in non-pregnant rats. This difference is due to a lower concentration of serum albumin and a higher concentration of non-esterified fatty acid (NEFA) that inhibits drug binding to albumin, in pregnant rats.…”

Section: Physical Development Parametersmentioning

confidence: 99%

Neurotoxicological study about a medicinal plant of Cissus sulcicaulis Baker in pregnancy rats

Magalhães

Marcondes

Duarte

et al. 2020

BJD

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The Cissus sulcicaulis Baker species belongs to the Vitaceae family is popularly used for its anti-inflammatory activity. This study investigated for the first time the reproductive capacity of pregnant rats exposed daily to Cissus sulcicaulis Baker, the fetal organogenesis (prenatal assay), and the development of the pups (postnatal assay). Pregnant rats were exposed for the entire gestational period to a saline solution (control), Cissus sulcicaulis Baker (0.2 or 0.4 g/kg/day) and diclofenac potassium (positive control-1.0 mg/kg/day). Fertility and pregnant weight gain were monitored. Pups were monitored for body weight, offspring vitality, morphology, and physical and neurobehavioral development. Cissus sulcicaulis Baker at a dose of 0.4 g/kg/day promotes alterations in reproductive performance of pregnant rats (p<0;05); at doses of 0.2 and 0.4 g/kg/day promoted morphologic changes in the offspring parameters (p<0;05); and in the dosage of 0.2 mg/kg/day significantly promotes neurotoxicity effects in the offspring (p<0;05). In conclusion, these results indicate that the exposure of rats, during pregnancy period, to the Cissus sulcicaulis Baker proved not to be safe.

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Section: Physical Development Parametersmentioning

confidence: 99%

Neurotoxicological study about a medicinal plant of Cissus sulcicaulis Baker in pregnancy rats

Magalhães

Marcondes

Duarte

et al. 2020

BJD

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“…Hepatic metabolites of DIC are 4‐hydroxy DIC and other hydroxylated forms which are eliminated from the body through the urine (65%) and bile (35%) after glucuronidation and sulfation (Small, ; Vane & Botting, ). Nevertheless, DIC is associated with severe adverse effects in gastrointestinal, lung, hepatic, and renal tissues (Brater, ; Miida et al, ; Pourjafar & Derakhshanfar, ; Tomic et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…DIC is associated with severe adverse effects in gastrointestinal, lung, hepatic, and renal tissues (Brater, 2002;Miida et al, 2008;Pourjafar & Derakhshanfar, 2004;Tomic et al, 2008).…”

mentioning

confidence: 99%

Ameliorative effects ofN‐acetyl cysteine on diclofenac‐induced renal injury in male rats based on serum biochemical parameters, oxidative biomarkers, and histopathological study

Nouri

Heidarian

2019

J Food Biochem

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Diclofenac (DIC) can cause nephrotoxicity in humans. In this study, we evaluated the protective effects of N‐acetyl cysteine (NAC) on DIC‐induced nephrotoxicity. Rats were assigned to four groups. Group 1 was control group; group 2 administrated with DIC only; group 3 administrated with DIC plus NAC and group 4 was treated with DIC and silymarin. Then, the oxidative biomarkers in serum and kidney were evaluated. In group 2, DIC caused a remarkable elevation (p < 0.05) in the levels of serum uric acid, TNF‐α, creatinine, urea, GOT, and GPT, protein carbonyl, malondialdehyde (MDA), and renal TNF‐α gene expression, relative to control group. In treated groups with NAC and silymarin, a noticeable reduction (p < 0.05) was seen in mentioned levels of biochemical parameters. NAC showed that it could reduce the abnormality of biochemical parameters and histopathological changes which is induced by DIC. Practical applications N‐acetyl cysteine (NAC) has a potential to ameliorate renal histopathological changes and improving renal activity of antioxidant enzymes in nephrotoxicity by diclofenac. Also, NAC has a potential to reduce inflammatory gene expression in the diclofenac‐induced nephrotoxicity. Additionally, NAC can be considered as an antioxidant which reduces renal MDA and serum protein carbonyl due to nephrotoxicity by diclofenac.

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“…The model was validated by evaluating the impact of increased AGP levels on propranolol, a drug known to have high binding affinity to AGP. 4,7,10,26,28,31,49 Ultimately, establishing this model will provide heightened visibility of the protein binding characteristics of drugs and yield more informed data interpretation.…”

mentioning

confidence: 99%

Alpha-1 Acid Glycoprotein as a Biomarker for Subclinical Illness and Altered Drug Binding in Rats

et al. 2021

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Alpha-1 acid glycoprotein (AGP) is a significant drug binding acute phase protein that is present in rats. AGP levels areknown to increase during tissue injury, cancer and infection. Accordingly, when determining effective drug ranges and toxicity limits, consideration of drug binding to AGP is essential. However, AGP levels have not been well established during subclinical infections. The goal of this study was to establish a subclinical infection model in rats using AGP as a biomarker. This information could enhance health surveillance, aid in outlier identification, and provide more informed characterization of drug candidates. An initial study (n = 57) was conducted to evaluate AGP in response to various concentrations of Staphylococcus aureus (S. aureus) in Sprague–Dawley rats with or without implants of catheter material. A model validation study (n = 16) was then conducted using propranolol. Rats received vehicle control or S. aureus and when indicated, received oral propranolol (10 mg/kg). Health assessment and blood collection for measurement of plasma AGP or propranolol were performed over time (days). A dose response study showed that plasma AGP was elevated on day 2 in rats inoculated with S. aureus at 106, 107 or, 108 CFU regardless of implant status. Furthermore, AGP levels remained elevated on day 4 in rats inoculated with 107 or 108 CFUs of S. aureus. In contrast, significant increases in AGP were not detected in rats treated with vehicle or 103 CFU S. aureus. In the validation study, robust elevations in plasma AGP were detected on days 2 and 4 in S. aureus infected rats with or without propranolol. The AUC levels for propranolol on days 2 and 4 were 493 ± 44 h × ng/mL and 334 ± 54 h × ng/mL, respectively), whereas in noninfected rats that received only propranolol, levels were 38 ± 11 h × ng/mL and 76 ± 16.h × ng/mL, respectively. The high correlation between plasma propranolol and AGP demonstrated a direct impact of AGP on drug pharmacokinetics and pharmacodynamics. The results indicate that AGP is a reliable biomarker in this model of subclinical infection and should be considered for accurate data interpretation.

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Decrease in protein binding and its effect on toxicokinetics (TK) / toxicodynamics (TD) of diclofenac and propranolol in pregnant rats

Cited by 6 publications

References 13 publications

Neurotoxicological study about a medicinal plant of Cissus sulcicaulis Baker in pregnancy rats

Neurotoxicological study about a medicinal plant of Cissus sulcicaulis Baker in pregnancy rats

Ameliorative effects ofN‐acetyl cysteine on diclofenac‐induced renal injury in male rats based on serum biochemical parameters, oxidative biomarkers, and histopathological study

Alpha-1 Acid Glycoprotein as a Biomarker for Subclinical Illness and Altered Drug Binding in Rats

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