Empagliflozin significantly ameliorated 5-fluorouracil-induced cardiotoxicity in rats, reducing serum troponin I from 74.4 U/L to 25.8 U/L and decreasing inflammation, oxidative stress, and apoptosis.
Does empagliflozin prevent 5-fluorouracil-induced cardiotoxicity in a rat model?
Empagliflozin ameliorates 5-fluorouracil-induced cardiotoxicity in rats by modulating SGLT2 and downregulating the TNFα/TLR/NF-κB signaling pathway.
Absolute Event Rate: 25.8% vs 74.4%
p-value: p=<0.05
One of the commoly used chemotherapeutic agents is 5-Fluorouracil (5-FU). Unfortunately, the clinical administration of 5-FU is complicated with serious cardiotoxic effects and the safe use becomes an urgent task in cardio-oncology. Till now, there are no studies discussed the role of empagliflozin (EMP) against 5-FU cardiotoxicity. Thus, we investigated this effect and the involved mechanisms in 5-FU induced heart injury. Forty male rats of Wistar albino species were used and divided randomly into four groups. Group I is the control group, group II is EMP given group, group III is 5-FU cardiotoxic group and group IV is 5-FU plus EMP group. 5-FU (150 mg/kg) was administered as a single intraperitoneal (i.p.) dose on 1st day to induce cardiotoxicity with or without EMP (30 mg/kg/d) orally for 5 days. The dose of 5-FU is relevant to the human toxic dose. Our data showed that 5-FU given group caused cardiotoxicity with significant increase of serum cardiac enzymes, toll like receptors, enhancement of nuclear factor kappa B (NF-κB), interleukin1β (IL1β), IL6, myeloid-differentiation-factor 88 (MYD88), heart weight, malondialdehyde (MDA), tumor-necrosis-factor-alpha (TNFα), sodium glucose co-transporter 2 (SGLT2), P53 and caspase3 expression with clear histopathological features of cardiotoxicity. Moreover, there is a significant decrease in reduced glutathione (GSH) and total antioxidant capacity (TAC). Interestingly, co-administration of EMP could ameliorate 5-FU induced biochemical and histopathological changes. This effect may be due to modulation of SGLT2, decreasing inflammation, oxidative stress and apoptosis with downregulation of an essential inflammatory cascade that mediates 5-FU cardiotoxicity; TNFα/TLR/NF-κB. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00204-1.
Refaie et al. (Tue,) conducted a other in 5-fluorouracil (5-FU)-induced cardiotoxicity (n=40). Empagliflozin vs. 5-fluorouracil alone (150 mg/kg single i.p. dose) was evaluated on Serum Troponin I (U/L) (p=<0.05). Empagliflozin significantly ameliorated 5-fluorouracil-induced cardiotoxicity in rats, reducing serum troponin I from 74.4 U/L to 25.8 U/L and decreasing inflammation, oxidative stress, and apoptosis.