Effect of dapagliflozin on rat liver ischemia-reperfusion injury
Volume 17, Issue 1, January 2026, Pages 47-55
Vahid Mahmoudi, Siamak Kazemi-Darabadi, Seyed Hosein Jarolmasjed, Monireh Khordadmehr
Abstract In recent years, liver transplantation has emerged as the standard therapy for several liver disorders. Throughout the procedure, the transplanted liver tissue is subjected to varying degrees of ischemia-reperfusion (IR) damage. Consequently, there has been a long-standing pursuit of substances that can alleviate the harm caused by IR. In our investigation, we employed dapagliflozin as a potential therapeutic agent. Eighteen Wistar rats were divided into three groups (n = 6), including treatment, IR, and control that did not undergo surgical intervention. Two days prior to surgery, the treatment group received dapagliflozin at a dosage of 10.00 mg kg-1 orally. During surgery, liver ischemia was induced for 1 hr, followed by a 24-hr reperfusion period. The IR group exhibited elevated levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, bilirubin, lactate dehydrogenase, and malondialdehyde compared to the control group. In contrast, the treatment group showed levels of these factors that were closer to those of the control group. While total protein, albumin, and total anti-oxidant capacity decreased in the IR group, this decline was less significant in the treatment group. Analysis of oxidative stress in liver tissue revealed that the treatment group had increased anti-oxidant capacity, and exhibited less oxidative stress compared to the IR group. Furthermore, dapagliflozin was found to reduce the degree of liver edema, necrosis, and vascular hyperemia following IR. Overall, dapagliflozin demonstrates the potential to lessen liver damage, enhance liver tissue regeneration, and mitigate the consequences associated with liver impairment.
Suppression of the malignancy of mammary tumor in mice model by inactivated preparation of Mycobacterium obuense
Volume 13, Issue 3, Summer 2022, Pages 393-401
Katayoon Nofouzi, Parsa Almasi, Ali Asghar Fakhri-Demeshgheieh, Monireh Khordadmehr, Behzad Baradaran, Milad Asadi, Parvin Sarbakhsh, Gholamreza Hamidian
Abstract Breast cancer (BC) is a significant cause of global mortality in women. This study was aimed to evaluate the immune-activation of malignant BC via the administration of attenuated Mycobacterium obuense. For this purpose, an in vivo model was developed with BALB/c mice. Mice were injected with 2.00 × 106 4T1 cells with breast tumor cell line. Forty-two mice were equally divided into control as well as low dose (0.20 mg 100 µL-1) and high dose (0.50 mg 100 µL-1) groups of M. obuense to investigate gene expression in the antitumor effects of M. obuense. In one group, paclitaxel was administrated as a choice drug in BC treatment. Antitumor manners were characterized by cytotoxicity against tumor target cells, size of the tumor and the expression of some BC metastatic genes together with pathology. The MTT assay demonstrated that different concentrations of both low and a high doses of bacteria did present no cytotoxicity effect on 4T1 cells. According to our findings, M. obuense significantly repressed tumor growth. M. obuense downregulated the expression of collagen type I alpha 1 (COLIA1), cFos, alkaline phosphatase (ALP), claudin 3 (cldn3), and conversely, activated transcription factor 4 (ATF4) and Twist related protein-1 (Twist1). All these alternations induced a decrease in the migratory and invasive capabilities of BC. The result of pathology was indicative of tumor regression in the paclitaxel and HK- M. obuense -recipient group. Thus, it seems most likely that M. obuense might impinge upon cell growth and metastatic behavior of malignant cells exerting anti-tumor activity in BC.
