Gadolinium Retention and Clearance in the Diabetic Brain after Administrations of Gadodiamide, Gadopentetate Dimeglumine, and Gadoterate Meglumine in a Rat Model.

PURPOSE: To evaluate gadolinium (Gd) retention and clearance in the brain of diabetic rats after administrations of gadodiamide, gadopentetate dimeglumine, and gadoterate meglumine. MATERIALS AND METHODS: Both diabetic rats (n = 52) and normal rats (n = 52) intravenously received 20 injections of 0.6 mmol Gd/kg gadodiamide, gadopentetate dimeglumine, gadoterate meglumine, or saline. Both diabetic rats and normal rats were divided into 2 subgroups of 24 and 28 rats for the 7-day and 42-day evaluations (i.e., they were sacrificed at 7 days (n = 6 per group) and 42 days (n = 7 per group)), respectively, after the last injection. For the 7-day subgroup, 6 rats were euthanized for inductively coupled plasma mass spectrometry (ICP-MS) analysis. For the 42-day subgroup, 6 rats underwent T1-weighted magnetic resonance imaging (MRI) and ICP-MS, and 1 rat was analyzed by transmission electron microscopy (TEM). RESULTS: The T1 enhancements in the deep cerebellar nuclei (DCNs) of diabetic rats were lower than those of normal rats in both linear Gd-based contrast agent (GBCA) groups (p < 0.05). The average Gd concentrations in the brains of diabetic rats were significantly lower than those of healthy rats in both the short-term groups and long-term groups (p < 0.05). The highest Gd retentions were in the olfactory bulb, DCN, and striatum with gadodiamide. Compared with the results obtained 7 days after the last injection, the residual Gd concentrations of the 42-day subgroups in the brains of diabetic rats showed no significant difference in both linear GBCA groups (p>0.05). CONCLUSIONS: Compared with normal rats, the diabetic status decreased the residual Gd concentrations in the brain after multiple administrations of gadodiamide, gadopentetate dimeglumine, and gadoterate meglumine. The clearable fraction of Gd in the brain was eliminated faster in diabetic rats than in normal rats.

17ß-Estradiol on the Expression of G-Protein Coupled Estrogen Receptor (GPER/GPR30) Mitophagy, and the PI3K/Akt Signaling Pathway in ATDC5 Chondrocytes In Vitro.

BACKGROUND Osteoarthritis is a progressive inflammatory joint disease resulting in damage to articular cartilage. G-protein coupled estrogen receptor (GPER/GPR30) activates cell signaling in response to 17ß-estradiol, which can be blocked by the GPR30 agonist, G15, an analog of G-1. The aims of this study were to investigate the effects of 17ß-estradiol on the expression of G-protein coupled estrogen receptor (GPER/GPR30) on mitophagy and the PI3K/Akt signaling pathway in ATDC5 chondrocytes in vitro. MATERIAL AND METHODS Cultured ATDC5 chondrocytes were treated with increasing concentrations of 17ß-estradiol with and without G15, p38 inhibitor (SB203580), JNK inhibitor (SP600125), PI3K inhibitor (LY294002, S1737), and mTOR inhibitor (S1842). Expression of GPER/GPR30 and components of the PI3K/Akt pathway in cultured ATDC5 chondrocytes were detected by immunofluorescence (IF) staining, Western blot, and real-time polymerase chain reaction (RT-PCR). Transmission electron microscopy (TEM) and IF were used to detect mitophagosomes. Expression of LC-3, LAMP2, TOM20, Hsp60, p-Akt, p-mTOR, p-p38, and p-JNK was investigated by Western blot. Proliferation and viability of the ATDC5 chondrocytes were determined using BrdU and MTT assays. RESULTS In 17ß-estradiol-treated ATDC5 chondrocytes, increased expression of GPER/GPR30 was found, but fewer mitophagosomes were observed, and decreased numbers of TOM20-positive granules were co-localized with decreased LAMP2 and increased expression levels of TOM20, Hsp60, p-Akt, and p-mTOR, and reduced expression of LC3-II, were found. In 17ß-estradiol-treated ATDC5 chondrocytes, the proliferation and viability of the 17ß-estradiol-treated ATDC5 chondrocytes were significantly elevated. CONCLUSIONS Treatment with 17ß-estradiol protected ATDC5 chondrocytes against mitophagy via the GPER/GPR30 and the PI3K/Akt signaling pathway.