Pharmacokinetics and repeated dose 28-day oral toxicity studies of acetaminophen nanosuspension.

Wide availability and easy accessibility of acetaminophen oral dosage forms increase the risk of intentional poisoning or unintentional organ toxicity, leading to a wide range of liver failure, nephrotoxicity, and neurotoxicity. In this study, an attempt was made to improve oral bioavailability and reduce the toxicity of acetaminophen using nanosuspension technology. The acetaminophen nanosuspensions (APAP-NSs) were prepared by a nano-precipitation method using polyvinyl alcohol and hydroxypropylmethylcellulose as stabilizers. The mean diameter of APAP-NSs was 124 ± 3.8 nm. The dissolution profile of APAP-NSs was significantly point-to-point higher than the coarse drug in simulated gastrointestinal fluids. The in vivo study revealed 1.6- and 2.8-fold increases in the AUC0-inf and Cmax of the drug, respectively, in APAP-NSs-receiving animals compared to the control group. Moreover, no deaths and no abnormalities in clinical signs, body weights, and necropsy findings were detected in the dose groups up to 100 mg/kg of the 28-day repeated oral dose toxicity study in mice.

Ovarian toxicity of plant-derived edible oils: a 28 days hormonal and histopathological study in Wistar rat.

Initial evidence on the endocrine-disrupting effects of genetically modified (GM) food motivated us to evaluate the reproductive toxicity of GM and non-GM plant-derived edible oils in female Wistar rats. Sunflower (non-GM), maize (GM), and canola (GM) oils as popular resource dietary oils were purchased from the local market. After tracking the target sequence of CaMV 35S and Nos terminator in all selected batch numbers of edible oils by real-time PCR, oil samples were daily gavaged to 10 weeks Wistar rats for 28 days. Clinical factors, serum lipid levels, sex hormones, and gonadotropins as well as the histopathological changes were compared among groups by statistical analysis. Besides normal lipid profile, gonadotropin levels, and LH/FSH ratio at day 28, serum estradiol levels were raised in both GM (canola oil (p=0.04)) and non-GM (sunflower oil (p=0.008)) groups. In necropsy studies, ovarian atrophies were detected in canola (p<0.001) and sunflower groups (p<0.043) although uterine remained unchanged in all groups. In histopathological evaluations, all sections showed severe congestion and multiple follicular cysts in the sunflower oil group. Simple and secondary cysts in the maize group were the other type of ovarian toxicity in this short period of time. Remarkable estrogenic properties of GM and non-GM plant-derived edible oils with signs of ovarian atrophy, congestion, and cysts may contribute to phthalate or other xenoestrogenic contaminations; therefore, analytical studies of samples and further human populations studies are highly recommended.