Vancomycin hydrochloride (VCM) is a glycopeptide antibiotic that is commonly used to eradicate methicillin-resistant gram-positive cocci, despite its nephrotoxic side effects. Elderly people are particularly susceptible to developing VCM-induced nephrotoxicity. However, the precise mechanism by which VCM induces nephrotoxicity in elderly people is not completely understood. Therefore, we investigated VCM-induced nephrotoxicity in mice of different ages. VCM was injected intraperitoneally into mice at 1, 3, 6, 12, and 24 months of age at a dosage of 400 mg/kg body weight for 3 and 14 days. Twenty-four hours after the last injection, we examined plasma creatinine levels and histopathological alterations in the kidneys. VCM administration increased plasma creatinine levels, and these values gradually increased to higher levels with aging. The histological examination revealed renal tubular degeneration, such as brush-border atrophy, apoptosis/necrosis of the tubular epithelium, and epithelial desquamation, that gradually became more severe with aging. Furthermore, immunohistochemical staining with anti-CD10 and anti-single-stranded DNA antibodies revealed damaged renal proximal tubules with marked dilatation, as well as numerous apoptotic cells, and these features increased in severity in 12- and 24-month-old mice receiving VCM. Based on these results, aged mice were highly susceptible to kidney damage induced by VCM administration. In addition, proximal tubular epithelial cells likely underwent apoptosis after the administration of VCM. This report is the first to document VCM-induced nephrotoxicity in mice of different ages. Thus, this mouse model could be useful for understanding the mechanisms of VCM-induced nephrotoxicity in the elderly.

Sweet potato is a crop that is widely consumed all over the world and is thought to contribute to health maintenance due to its abundant nutrients and phytochemicals. Previous studies on the functionality of sweet potatoes have focused on varieties that have colored pulp, such as purple and orange, which contain high levels of specific phytochemicals. Therefore, in the present study, we evaluated the anti-inflammatory effects of light-yellow-fleshed sweet potatoes, which have received little attention. After freeze-drying sweet potatoes harvested in 2020, extracts were prepared from the leaves, stems, roots, and tubers in 100% ethanol. Mouse macrophage-like cell line RAW264.7 cells were cultured with 10 µg/mL of the extracts and induced lipopolysaccharide (LPS)-stimulated inflammation. Of the extracts, the tuber extracts showed the highest suppression of LPS-induced interleukin-6 (IL-6) gene expression and production in RAW264.7, which was attributed to the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) oxidative stress response pathway. In addition, preparative high-performance liquid chromatography (HPLC) experiments suggested that hydrophobic components specific to the tuber were the main body of activity. In previous studies, it has been shown that the tubers and leaves of sweet potatoes with colored pulp exhibit anti-inflammatory effects due to their rich phytochemicals, and our results show that the tubers with light-yellow pulp also exhibit the effects. Furthermore, we were able to show a part of the mechanism, which may contribute to the fundamental understanding of the treatment and prevention of inflammation by food-derived components.

Peptidylarginine deiminases (PADs) are posttranslational modification enzymes that citrullinate (deiminate) protein arginine residues in a calcium-dependent manner, yielding citrulline residues. Enzymatic citrullination abolishes positive charges of native protein molecules, inevitably causing significant alterations in their structure and function. Previously, we reported the abnormal accumulation of citrullinated proteins and an increase of PAD2 content in hippocampi of patients with Alzheimer disease. In this study, we investigated PAD expression by using dibutyryl cAMP (dbcAMP) in human astrocytoma U-251MG cells. Under normal culture conditions, PAD2 and PAD3 mRNA expression is detectable with quantitative PCR in U-251MG cells. The addition of dbcAMP in a dose-dependent manner significantly increased this mRNA expression and protein levels. Moreover, PAD enzyme activity also increased significantly and dose-dependently. Furthermore, the expression of PAD2 and PAD3 mRNA was inhibited by the cAMP-dependent PKA inhibitor KT5720, suggesting that such expression of dbcAMP-induced PAD2 and PAD3 mRNA is mediated by the cAMP-PKA signaling pathway in U-251MG cells. This is the first report to document the PAD2 and PAD3 mRNA expression induced by dbcAMP and to attribute the induction of these genes to mediation by the cAMP-PKA signaling pathway in U-251MG cells. © 2016 Wiley Periodicals, Inc.

Superoxide dismutase 1 (SOD1) is an antioxidant enzyme that converts superoxide anion radicals into hydrogen peroxide and molecular oxygen. The senescence marker protein-30 (SMP30) is a gluconolactonase that functions as an antioxidant protein in mammals due to its involvement in ascorbic acid (AA) biosynthesis. SMP30 also participates in Ca(2+) efflux by activating the calmodulin-dependent Ca(2+)-pump. To reveal the role of oxidative stress in lipid metabolism defects occurring in non-alcoholic fatty liver disease pathogenesis, we generated SMP30/SOD1-double knockout (SMP30/SOD1-DKO) mice and investigated their survival curves, plasma and hepatic lipid profiles, amounts of hepatic oxidative stress, and hepatic protein levels expressed by genes related to lipid metabolism. While SMP30/SOD1-DKO pups had no growth retardation by 14 days of age, they did have low plasma and hepatic AA levels. Thereafter, 39% and 53% of male and female pups died by 15-24 and 89 days of age, respectively. Compared to wild type, SMP30-KO and SOD1-KO mice, by 14 days SMP30/SOD1-DKO mice exhibited: (1) higher plasma levels of triglyceride and aspartate aminotransferase; (2) severe accumulation of hepatic triglyceride and total cholesterol; (3) higher levels of superoxide anion radicals and thiobarbituric acid reactive substances in livers; and (4) decreased mRNA and protein levels of Apolipoprotein B (ApoB) in livers - ApoB is an essential component of VLDL secretion. These results suggest that high levels of oxidative stress due to concomitant deficiency of SMP30 and/or AA, and SOD1 cause abnormal plasma lipid metabolism, hepatic lipid accumulation and premature death resulting from impaired VLDL secretion.