Isoniazid (INH) remains the core drug in tuberculosis management, but serious hepatotoxicity and potentially fatal liver injury continue to accompany INH consumption. Among numerous theories that have been established to explain INH-induced liver injury, an inflammatory stress theory has recently been widely used to explain the idiosyncrasy. Inflammatory stress usually sensitizes tissues to a drug's toxic consequences. Therefore, the present study was conducted to verify whether bacterial lipopolysaccharide (LPS)-induced inflammation may have a role in enhancing INH hepatotoxicity. While single INH or LPS administration showed no major toxicity signs, INH-LPS cotreatment intensified liver toxicity. Both blood biomarkers and histological evaluations clearly showed positive signs of severe liver damage accompanied by massive necrosis, inflammatory infiltration, and hepatic steatosis. Furthermore, elevated serum levels of bile acid associated with the repression of bile acid synthesis and transport regulatory parameters were observed. Moreover, the principal impact of cytochrome P450 2E1 (CYP2E1) on INH toxicity could be anticipated, as its protein expression showed enormous increases in INH-LPS-cotreated animals. Furthermore, the crucial role of CYP2E1 in the production of reactive oxygen species (ROS) was clearly obvious in the repression of hepatic antioxidant parameters. In summary, these results confirmed that this LPS-induced inflammation model might prove valuable in revealing the hepatotoxic mechanisms of INH and the crucial role played by CYP2E1 in the initiation and propagation of INH-induced liver damage, information which could be very useful to clinicians in understanding the pathogenesis of drug-induced liver injury.
Pristimerin, a natural triterpenoid isolated form Celastrus and Maytenus spp, has been shown to possess a variety of biological and pharmacological effects. Recently, pristimerin has attracted more attention, especially for its potential anticancer activities. The anticancer activities of pristimerin have been illustrated in various cancer cell lines and animal models. It has been found to inhibit in vitro and in vivo proliferation, survival, angiogenesis and metastasis of tumor cells. These activities have been attributed to its modulation of various molecular targets such as cyclins, apoptosis- related proteins, proteasome activity, reactive oxygen species, as well as NF-κB, AKT/mTOR and MAPK/ERK pathways. This mini-review discussed the cellular impact and animal studies of pristimerin treatment, with more attention on the various molecular targets of pristimerin.
1 February 2022 in Advances in Medical Education and Practice
Background: Academic stress is a common problem among medical students, and the COVID-19 health crisis lockdown further worsened it. High academic stress has a negative impact on students learning and overall performance. Objective: To assess perceived academic stress, causes, and coping strategies among undergraduate pharmacy students during the COVID-19 pandemic. Methods: A descriptive cross-sectional study was conducted among undergraduate pharmacy students at the University of Khartoum. Data were collected from randomly selected participants using three validated self-administered questionnaires; perceived stress scale, study habits inventory, and mental health inventory. Data were analyzed using SPSS software, and descriptive statistics and chi-square were employed. Results: The response rate in our study was 99.6% (251/252). About 87% of the participants were females. The majority of participants (92%) experience academic stress, with a mean score (24.99 ± 5.159), the level of academic stress ranging from low (4.3%), moderate (73.2%), to high (22.5%). Approximately 80% of the percipients reported academic stress during all exam times with a mean score (25.33 ± 4.976). The level of academic stress was significantly associated with participants’ gender (P-value: 0.042), and living conditions (P-value: 0.001). The most common factors that were significantly associated with academic stress were difficulty in remembering all that is studied (66.7%, P=0.006) and worrying about the exams (54.1%, P=0.011). Moreover, the most frequent strategies used to cope with academic stress were praying (84.4%) and maintaining some control over the situation (61.9%). Conclusion: The study revealed a high prevalence of academic stress among percipients. Academic counseling, monitoring of mental status, and implementation of stress reduction programs are highly recommended.