Key result
Agomelatine significantly reduced oxidative stress, inflammatory markers (MDA, NOx, IL-6, STAT3), and histological damage in methotrexate-induced lung and intestinal toxicity in rats.
Why the study?
Methotrexate is linked to multiple organ toxicity, and acute toxic symptoms can negatively affect patient commitment to treatment.
Does agomelatine prevent methotrexate-induced lung and intestinal toxicity in male Wister rats?
RCT (n=48)
randomized
Does agomelatine prevent methotrexate-induced lung and intestinal toxicity in male Wister rats?
Agomelatine demonstrates protective effects against methotrexate-induced lung and intestinal toxicity in a rat model.
Agomelatine attenuates methotrexate toxicity in rats; hypothesis-generating and should not change practice pending human data.
BACKGROUND: Methotrexate (MTX), an anticancer drug, has been linked to multiple organ toxicity. The drug-induced acute toxic symptoms can negatively affect the patient's commitment to the course of treatment. MATERIALS AND METHODS: This study aimed to investigate the mitigating action of agomelatine (Ago) against MTX-induced lung and intestinal toxicity. Forty eight male Wister rats were randomized into six experimental groups: Group 1: Control; Groups 2 and 3: received Ago L&H (20/40 mg/kg, respectively by gavage); Group 4: received MTX 10 mg/kg/day, i.p. on days 7-9; Group 5: received Ago L (20 mg/kg) + MTX; Group 6: received Ago H (40 mg/kg) +MTX. The duration of the study was 10 days. Lung/intestine oxidative markers were measured. Lung/intestinal tissues IL-6, STAT3, and HO-1 levels were evaluated by ELISA. Besides, lung/intestinal tissues were examined for Histological changes, collagen fibers detection using Massonꞌs trichome stain, and immunohistochemical study using HSP70 antibody. RESULTS: MDA, NOx, IL-6, and STAT3 levels were significantly higher in the MTX group's lungs and intestines, indicating lung and intestinal toxicity. There were substantial decreases in GSH, SOD tissue levels, and HSP 70 immunoexpression, as well as histological changes suggesting significant lung and intestinal injury. All of the above parameters improved significantly by using Ago. CONCLUSION: By reducing oxidative stress, inflammatory processes, and modulating the IL-6/STAT3 pathway, Ago has potent ameliorative effects against MTX-induced lung/intestinal toxicities.
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Kamel et al. (2021) conducted an RCT in Methotrexate-induced lung and intestinal toxicity (n=48). Agomelatine vs. Methotrexate alone and Control was evaluated on Lung/intestine oxidative markers, IL-6, STAT3, HO-1 levels, and histological changes. Agomelatine significantly reduced oxidative stress, inflammatory markers (MDA, NOx, IL-6, STAT3), and histological damage in methotrexate-induced lung and intestinal toxicity in rats.