Carvacrol mitigates vancomycin-induced nephrotoxicity via regulation of IkBα/p38MAPK and Keap1/Nrf2 signaling pathways: an experimental study with in silico evidence.

OBJECTIVE: Despite its evident renal toxicity, vancomycin is considered an effective glycopeptide antibiotic against life-threatening positive bacterial contagions. The current study aimed to investigate the potential protective effects of carvacrol as well as its underlying mechanism against vancomycin-induced nephrotoxicity. MATERIALS AND METHODS: The animals were randomly classified into four groups (8 rats per group). Group I, which served as a control group, received only vehicles. Group II received a single i.p. injection of 50 mg/kg of carvacrol for seven days. Group III received vancomycin (200 mg/kg, i.p.) as a singular daily dose for seven days. Carvacrol was administered to Group IV seven days prior to the daily vancomycin dose. RESULTS: The results revealed that carvacrol minimized vancomycin-induced renal injury as evidenced by lower serum cystatin C levels and kidney injury molecule-1 (KIM-1), in addition to a decline in renal damage caused by vancomycin as indicated in histopathological assessment. Furthermore, carvacrol significantly attenuated oxidative stress parameters and inflammatory mediators. Moreover, it downregulated Keap1, mitogen-activated protein kinase (p38MAPK), and nuclear factor kappa B (NF-κB) genes and proteins, along with controlling the NF-κB inhibitory protein (IkBα) and nuclear factor erythroid 2-related factor 2 (Nrf2) genes and proteins observed through streaming its genes. A molecular docking technique was also used to investigate the potential interactivity between carvacrol and proteins involved in regulating oxidative injury and inflammatory responses. CONCLUSIONS: The current study findings revealed that carvacrol administration before vancomycin could be a promising therapeutic approach for maceration of renal damage stimulated by vancomycin via controlling IkBα/MAPK and Keap1/Nrf2 signaling molecules.https://www.europeanreview.org/wp/wp-content/uploads/graphical-abstract-1.jpg.

Multiple targets of Nrf 2 inhibitor; trigonelline in combating urethane-induced lung cancer by caspase-executioner apoptosis, cGMP and limitation of cyclin D1 and Bcl2.

OBJECTIVE: Among other types of cancerous lesions, lung cancer is one of the prevalent causes of death. Trigonelline is a plant alkaloid, a significant constituent in coffee, and has shown health benefits in several disorders. The present study aims to investigate the potential therapeutic role of trigonelline in lung cancer. MATERIALS AND METHODS: Seventy-five BALB/C mice were assigned to five groups and treated for 150 days as follows (1): normal control group; (2) trigonelline only (50 mg/kg/ P.O) daily for the last thirty days; (3) urethane (1.5 g/kg B.w/i.p) at day one and sixty; (4) urethane and carboplatin (15 mg/kg i.p) for the last thirty days; and (5) urethane and trigonelline for the last thirty days. Tumor size was measured while blood and lung were collected for biochemical, western blotting analysis, and histological examinations. RESULTS: Urethane demonstrated significant changes in all biochemical and molecular parameters and histological examinations. In animals pretreated with urethane, trigonelline significantly reduced tumor size and restored Nrf2, NF-кB p65, Bcl-2, Cyclin D1, ICAM-1, and MMP-2, along with improving cGMP and active caspase three and refining histological architectures. CONCLUSIONS: Nrf2 signaling may be a promising therapeutic target for adenocarcinoma protection or management. Due to its multiple therapeutic effects on Nrf2, cyclin D1, NF-кB pathways, and the BAX/Bcl2 axis, trigonelline significantly induced cell cycle arrest and apoptosis.https://www.europeanreview.org/wp/wp-content/uploads/Graphical_Abstract-1.jpg.