Propionic acid (PRA) is a metabolic end-product of enteric bacteria in the gut, and it is commonly used as a food preservative. Despite the necessity of PRA for immunity in the body, excessive exposure to this product may result in disruptive effects. The purpose of this study is to examine the hepatoprotective effects of acetyl-L-carnitine (A-CAR) and liposomal-coenzyme Q10 (L-CoQ10) against PRA-induced injury. Liver injury in rats was induced by oral administration of PRA, and A-CAR and L-CoQ10 were administered concurrently with PRA for 5 days. Oxidative stress, inflammatory, apoptotic, and fibrotic biomarkers were analyzed; the histology of liver tissue was assessed as well to further explore any pathological alterations. PRA caused significant increases in the levels of serum liver enzymes and hepatic oxidative stress, inflammatory, and apoptotic biomarker levels, along with histopathological alterations. Concurrent treatment with A-CAR and/or L-CoQ10 with PRA prevented tissue injury and decreased the levels of oxidative stress, proinflammatory cytokines, and apoptotic markers. Additionally, A-CAR and/or L-CoQ10 modulated the expression of high-mobility group box-1, cytokeratin-18, transforming growth factor-beta1, and SMAD3 in liver tissue. In conclusion, A-CAR and/or L-CoQ10 showed hepatoprotective efficacy by reducing oxidative stress, the inflammatory response, apoptosis, and fibrosis in liver tissue.
Apixaban and rivaroxaban require lead-in dosing for 7 and 21 days, respectively, when treating venous thromboembolism (VTE). However, no evidence exists to support subtracting parenteral anticoagulation days from total lead-in dosing. A multicenter study was conducted, including adult patients with acute VTE who received apixaban or rivaroxaban. The patients were grouped as follows. The recommended group received oral lead-in anticoagulant for the full recommended duration. The mixed group received lead-in therapy as parenteral with oral anticoagulant. The incidence of recurrent VTE (rVTE) and major bleeding (MB) within 90 days were the main outcomes. Of the 368 included patients, 47.8% received apixaban, and 52.2% received rivaroxaban. The recommended lead-in was used in 296 patients (80.4%), whereas 72 (19.6%) received the mixed-lead-in regimen. Five patients had rVTE events within 90 days; two occurred during hospitalization in the recommended group versus none in the mixed group (0.7% vs. 0.0%; p = 1.000). After discharge, two events occurred in the recommended group and one in the mixed group (0.7% vs. 1.4%; p = 0.481). In terms of MB, 24 events occurred in 21 patients within 90 days. During hospitalization, 11 events occurred in the recommended group and seven in the mixed group (3.7% vs. 9.7%; p = 0.060). After discharge, five more events occurred in the recommended group and one in the mixed group (1.4% vs. 1.7%; p = 1.000). The mixed-lead-in regimen is safe and effective in comparison with the recommended-lead-in regimen.
Background Although parenteral anticoagulation lead-in is not recommended with apixaban and rivaroxaban, parenteral anticoagulation is often used to replace apixaban or rivaroxaban lead-in doses for the initial phase treatment of VTE. Thus, our study compares the safety and effectiveness of lead-in parenteral anticoagulation to lead-in apixaban or rivaroxaban in patients who received apixaban or rivaroxaban for VTE treatment. Methods A multi-center retrospective cohort study included adult patients (aged ≥ 18 years) admitted to the hospital with acute VTE and treated with either apixaban or rivaroxaban. Patients were grouped depending on the lead-in anticoagulation received for initial VTE treatment into the “Direct oral anticoagulation (DOAC) lead-in” group if patients received an appropriate lead-in dose of apixaban and rivaroxaban and patients who received parenteral lead-in the “parenteral lead-in” group. Results A total of 389 patients were included; the DOAC lead-in group included 296 patients, whereas 93 patients were in the parenteral lead-in group. VTE recurrence (rVTE) during hospitalization and within 30 days was numerically higher in the parenteral lead-in group compared to the DOAC lead-in group (3.3% vs 0.6%; p =0.09 and 1.1% vs 0.7%; p =0.560), with a significantly higher number of patients with rVTE at 90 days (5.4% vs 1.4%; p =0.039). However, none of the patient’s characteristics were significantly associated with the incidence of rVTE. In addition, the major bleeding rate during hospitalization was significantly higher among the parenteral lead-in group than in the DOAC lead-in group (14.0% vs 3.7%; p <0.001). Conclusion Parenteral anticoagulation lead-in before starting maintenance of apixaban and rivaroxaban showed a significantly higher risk of bleeding and a trend toward higher VTE recurrence than the DOAC lead-in. This study adds to the evidence supporting the utilization of the DOAC lead-in regimen in treating patients with VTE. Still, larger studies with robust designs are needed to confirm these findings.
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