Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism-Effects of Calcitriol Supplementation.

Vitamin D deficiency or insufficiency is prevalent in childhood cancer patients and survivors after chemotherapy; further studies are needed to investigate the underlying aetiology and effectiveness of vitamin D supplementation in preventing chemotherapy-induced bone loss. This study used a rat model of treatment with antimetabolite methotrexate to investigate whether methotrexate chemotherapy causes vitamin D deficiency and if vitamin D supplementation attenuates the resultant bone loss. Methotrexate treatment (five daily injections) decreased serum vitamin D levels (from 52 to <30 ng/mL), reduced body and bone lengthening and tibial trabecular bone volume, and altered intestinal vitamin D metabolism, which was associated with intestinal mucosal damage known to cause malabsorption of nutrients, including dietary vitamin D and calcium. During the early stage after chemotherapy, mRNA expression increased for vitamin D activation enzyme CYP27B1 and for calcium-binding protein TRPV6 in the intestine. During the intestinal healing stage, expression of vitamin D catabolism enzyme CYP24 increased, and that of TRPV6 was normalised. Furthermore, subcutaneous calcitriol supplementation diminished methotrexate-induced bone loss due to its effect suppressing methotrexate-induced increased bone resorption. Thus, in young rats, methotrexate chemotherapy causes vitamin D deficiency, growth impairments, bone loss, and altered intestinal vitamin D metabolism, which are associated with intestinal damage, and vitamin D supplementation inhibits methotrexate-induced bone loss.

Is Chemerin associated with gestational diabetes mellitus? An evidence-based clinical research from Chinese women.

The present study aimed to explore the association between gestational diabetes mellitus (GDM) and Chemerin, by analysing Chemerin level, clinical data and biochemical parameters among 46 GDM patients and 43 controls. It was found that the Chemerin levels from cord blood, peripheral blood, adipose tissue and placenta tissue were all significantly higher in the GDM group than those in the control group (p < .05 for all). Maternal insulin resistance (IR) index and serum inflammation parameters, including C-reactive protein and white blood cells, were also higher in GDM group (p < .05 for all). Moreover, maternal IR index and circulating insulin level were both positively correlated with maternal circulating Chemerin level (p < .05 for both). Our findings suggest that Chemerin, associated with IR and more expressed in GDM women, might participate in the pathogenesis of GDM. Impact Statement What is already known on this subject: Chemerin, a recently-discovered adipocytokine, has been widely-considered to be involved in metabolic diseases, and several studies have investigated it in gestational diabetes mellitus (GDM), but with no consensus about the level comparison between GDM and controls. What the results of this study add: The present case-control study found that the levels of Chemerin from cord blood, peripheral blood, adipose tissue and placenta tissue were all significantly higher in the GDM group. What the implications are of these findings for clinical practice and/or further research: Also, the circulating Chemerin level was positively correlated with insulin index, which we thought would add to the evidence that Chemerin does be associated with GDM, contributing to elucidating the pathogenesis of GDM.

Steamed root of Rehmannia glutinosa Libosch (Plantaginaceae) alleviates methotrexate-induced intestinal mucositis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Intestinal mucositis induced by chemotherapy is a severe clinical problem in cancer patients that currently lack effective interventions. In traditional Chinese medicine, chemotherapeutic toxicity is diagnosed as Qi and Yin deficiency, and steamed rehmannia root (SRR) is frequently prescribed to these patients. Whether SRR can prevent the adverse effects remains to be confirmed experimentally. The present study used a rat model to investigate potential efficacy and action mechanisms of SRR in attenuating the adverse effects caused by chemotherapy. MATERIALS AND METHODS: Intraperitoneal injection of a single dose of anti-metabolite methotrexate (MTX, 25mg/kg) was given to adult Wistar rats, which also received oral gavage of water or SRR (1.08g/kg twice daily 3 days before and 4 days after MTX treatment), or calcium folinate (CF, a clinically used MTX antidote as a comparison, at 1mg/kg twice daily 36h after MTX treatment), or SRR and CF in combination. Animals were sacrificed 4 days after MTX treatment. Complete blood cell counting was carried out. Jejunum was analyzed histologically for mucosal damage, immunohistochemically for proliferating cell nuclear antigen (PCNA), and biochemically for thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH), as well as for tumor necrosis factor alpha (TNF-α). RESULTS: MTX treatment led to weight loss, leucopenia, polycythemia, increase in large thrombocyte ratio, intestinal villus atrophy, crypt loss and reduction in PCNA positive crypt cells, increases in mucosal TBARS and TNF-α and decrease in GSH. All these alterations were inhibited by SRR administration except leucopenia, and the effects of CF or CF plus SRR supplementation were found to be inferior to those of SRR. CONCLUSIONS: SRR can alleviate MTX-induced gut mucositis, which may be achieved by inhibiting MTX-induced oxidative stress and inflammatory response. These findings support the application of SRR in chemotherapy but not the combined application of SRR and CF.