Key result
Low-dose gamma irradiation, especially combined with telmisartan, attenuated cyclophosphamide-induced cardiotoxicity in rats by modulating the NF-κB signaling pathway and pro-inflammatory cytokines.
Why the study?
Cyclophosphamide causes dose-limiting multi-organ toxicities, prompting interest in whether low-dose gamma radiation alone or combined with telmisartan protects against cyclophosphamide-induced cardiotoxicity.
Does low-dose gamma irradiation alone or combined with telmisartan prevent cyclophosphamide-induced cardiotoxicity in rats?
Does low-dose gamma irradiation alone or combined with telmisartan prevent cyclophosphamide-induced cardiotoxicity in rats?
Answers are grounded in this paper and cite their sources.
Low-dose gamma irradiation, particularly when combined with telmisartan, shows potential in mitigating cyclophosphamide-induced cardiotoxicity in a rat model.
PURPOSE: Cyclophosphamide (Cyp) is one of the most commonly used, wide spectrum chemotherapeutic agents. Cyp has multi-organ toxicities that are dose limiting, thus it's mostly used in chemotherapeutic combinations. Radiation is well known as a hazardous sort of energy, recent studies are interested in studying the beneficial therapeutic effects of low-dose gamma radiation. This study examined the protective effect of two different doses/dose-rates of irradiation either alone or combined with telmisartan against Cyp-induced cardiotoxicity. MATERIALS AND METHODS: Rats were divided into seven groups; (1): Control, (2): Cyp, (3-4): 0.05 Gy low dose rate (LDR) irradiation, 0.25 Gy high dose rate (HDR) irradiation, respectively, prior to Cyp dose, (5-7): telmisartan either alone or with 0.05 Gy LDR-irradiation or 0.25 Gy HDR-irradiation, respectively, prior to Cyp dose. The current investigation studied the effect of Cyp alone or combined with different treatment regimens on serum cTn-I and LDH, nuclear factor-κB (NF-κB) pathway (p65/IκB/IKK-α/IKK-ß) in the myocardium. Pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α were assessed in addition to histopathological examination of the heart. RESULTS: Low-dose irradiation attenuated cardiac enzymes, pro-inflammatory cytokines, NF-κB content, and histology, in both low and HDRs. Furthermore, the combination of low-dose irradiation with telmisartan (an angiotensin-II receptor type-1 blocker and a known cardio-protective drug) offered the best histological results. CONCLUSIONS: Low-dose irradiation-induced amelioration is partially but not completely through canonical activation of NF-κB, and may have another atypical pathway. While telmisartan probably ameliorates NF-κB totally through canonical pathway.
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Abd-ElRaouf et al. (2021) studied Cyclophosphamide-induced cardiotoxicity. Low-dose gamma irradiation alone or combined with telmisartan vs. Control and Cyclophosphamide alone was evaluated on Serum cTn-I, LDH, NF-κB pathway, pro-inflammatory cytokines, and histopathology. Low-dose gamma irradiation, especially combined with telmisartan, attenuated cyclophosphamide-induced cardiotoxicity in rats by modulating the NF-κB signaling pathway and pro-inflammatory cytokines.
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