Liraglutide Attenuates Diabetic Cardiomyopathy via the ILK/PI3K/AKT/PTEN Signaling Pathway in Rats with Streptozotocin-Induced Type 2 Diabetes Mellitus.

One of the possible candidates for the treatment of diabetic cardiomyopathy is liraglutide, a glucagon-like peptide-1 receptor (GLP1R) agonist. In this study, the impacts of liraglutide on the integrin-linked kinase (ILK)-related PI3K/AKT axis in rats with type 2 diabetes induced via streptozotocin were examined. Twenty-four Wistar albino rats were distributed in four different groups, and a high-fat diet and streptozotocin were used to induce type 2 in two groups. Rats in the untreated control groups were administered 0.9% NaCl solution over a 6-week period, and those in the treatment groups were administered 0.9% NaCl for 3 weeks, followed by subcutaneous injection of liraglutide (150 µg/kg) for an additional 3 weeks. In the liraglutide-treated diabetic group, the heart-to-body weight ratio was significantly reduced, levels of cardiac biomarkers, troponin I and creatine-kinase-MB, were improved; activities of antioxidant enzymes, glutathione peroxidase and superoxide dismutase, were increased; and levels of malondialdehyde were decreased. Western blotting and immunohistochemical studies revealed increased levels of ILK, P-PI3K, P-AKT, and BCL2, as well as those of caspase 3, BAX, and P-PTEN, indicating mitigation of cardiomyocyte apoptosis. Our results show that liraglutide, by targeting GLP1Rs, enhances the expression of proteins in the ILK/PI3K/AKT/PTEN pathway and thereby exerts its cardioprotective effects in rats with DCM.

Determination of dose- and time-dependent hepatotoxicity and apoptosis of Lanthanum oxide nanoparticles in female Swiss albino mice.

Nanosized lanthanum oxide particles (La2O3) are commonly utilized in various industries. The potential health risks associated with La2O3 nanoparticles, cytotoxic effects at varying doses and time intervals, and the mechanisms behind their induction of behavioral changes remain uncertain and necessitate further investigation. Therefore, this study examined in vivo hepatotoxicity, considering the quantity (60, 150, and 300 mg/kg) and time-dependent induction of reactive oxygen species (ROS) over one week or 21 days. The mice received intraperitoneal injections of three different concentrations in Milli-Q water. Throughout the experiments, no physical changes or weight loss were observed among the groups. However, after 21 days, only the highest concentration showed signs of anxiety in the activity cage (p < 0.05). Subsequently, all animals treated with La2O3 NPs exhibited a significant loss of learning and memory recall using the Active Avoidances test, after 21 days (p < 0.001). Markers for anti-reactive oxygen species (ROS) such as superoxide dismutase (SOD) were significantly upregulated in response to all concentrations of NPs after seven days compared to the control group. This was confirmed by a significant increase in glutathione peroxidase (Gpx1) and pro-apoptotic Caspase-3 expression at the lowest and highest doses. Additionally, both transcription and protein levels of the anti-apoptotic BCL-2 surpassed P53 protein in a dosage-dependent manner, indicating activation of the primary anti-apoptosis pathway. After 21 days, P53 levels exceeded BCL-2 protein levels, confirming a significant loss of BCL-2 mRNA, particularly at the 300 mg/kg concentration. Furthermore, a higher transcription level of Caspase-3, SOD, and Gpx1 was observed, with the highest values detected at the 300 mg/kg concentration, indicating the activation of cell death. Histopathological analysis of the liver illustrated apoptotic bodies resulting from La2O3 NP concentration. The investigation revealed multiple inflammatory foci, cytoplasmic degeneration, steatosis, and DNA fragmentation consistent with increased damage over time due to higher concentrations. Blood samples were also analyzed to determine liver enzymatic changes, including alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), and lipid profiles. The results showed significant differences among all La2O3 NP concentrations, with the most pronounced damage observed at the 300 mg/kg dose even after 21 days. Based on an animal model, this study suggests that La2O3 hepatotoxicity is likely caused by the size and shape of nanoparticles (NPs), following a dose and time-dependent mechanism that induces the production of reactive oxygen species and behavioral changes such as anxiety and memory loss.

Efficacy of ivermectin against colon cancer induced by dimethylhydrazine in male wistar rats.

Colon cancer (CC) is a common form of cancer worldwide. According to growing incidence of cancer and little information about the possible protective role of Ivermectin (IVM) on colon cancer, this study aimed to investigate the chemoprotective role of IVM against colon cancer induced by Dimethylhydrazine (DMH) in Male Wistar Rats. Based on LD50, three doses of IVM (0.25, 0.5, and 1 mg/kg) were applied before assayingthe antioxidant status, apoptotic markers, and microscopic analysis. Our result showed that glutathione (GSH) level was significantly increased in low dose of IVM-treated rats. Hight levels of oxidative stress and tissue damage consumed GSH and catalase (CAT), and dismutase (SOD) as indicated by significant drop in the treated groups. mRNA levels of Bax and caspase-3 were upregulated in rats treated with the high dose. Contrastingly, the expression of Bcl-2 was significantly downregulated with high dose. Changes in genes expression proved that IVM triggered apoptosis in treated groups compared to untreated control group. Microscopic analysis showed that rats treated with DMH exhibited high development of colorectal tumor. After induction of colorectal tumor, medium and high dose of DMH induced reduction in medullary carcinoma with great incidence of lymphoid nodules and desmoplastic reaction. In conclusion, this study demonstrates the potential of IVM as an anticancer drug against colon cancer in male Wistar rats.