Flumequine is a fluoroquinolone antibiotic with favorable bioavailability and acts as an inhibitor of topoisomerase II, with an IC50 value of 15μM[1,2]. Flumequine exerts its antibacterial effect by inhibiting bacterial DNA gyrase, thereby blocking DNA replication[3], and is commonly used in the treatment of intestinal infections in livestock and fish[4,5].
In vitro, treatment of B16F10 mouse melanoma cells with Flumequine (12.5, 25, 50μM) for 72h increased extracellular melanin content by 6.1 ± 1.6%, 9.4 ± 0.5%, and 11.6 ± 0.3%, respectively, and intracellular melanin content by 42.2 ± 3.6%, 58.1 ± 1.0%, and 59.1 ± 0.6%, respectively. Treatment with Flumequine (50μM) for 48h significantly upregulated the mRNA expression levels of microphthalmia-associated transcription factor (MITF) and tyrosinase in B16F10 cells[6].
In vivo, oral administration of Flumequine (750mg/kg; once daily) to pubertal male Wistar rats for six weeks significantly reduced serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). From day 7 of treatment onward, body weight gain was significantly slowed, and the relative weights of the brain, adrenal glands, thyroid gland, and testes were significantly increased[7]. In rainbow trout infected with red mouth disease, oral administration of Flumequine (12mg/kg/day) via medicated feed for 8 days resulted in a significant increase in the proportion of Flumequine-resistant Aeromonas spp. on the skin and in the gut contents of the fish at 24h post-treatment[8].
References:
[1] GIGUÈRE S, DOWLING P M. Fluoroquinolones[J]. Antimicrobial therapy in veterinary medicine, 2013: 295-314.
[2] KASHIDA Y, SASAKI Y F, OHSAWA K, et al. Mechanistic study on flumequine hepatocarcinogenicity focusing on DNA damage in mice[J]. Toxicological Sciences, 2002, 69(2): 317-321.
[3] ALDRED K J, KERNS R J, OSHEROFF N. Mechanism of quinolone action and resistance[J]. Biochemistry, 2014, 53(10): 1565-1574.
[4] RODRÍGUEZ J M, DIEZ M J, SIERRA M, et al. Distribution of flumequine in intestinal contents and colon tissue in pigs after its therapeutic use in the drinking water[J]. Animals, 2021, 11(6): 1514.
[5] TOURAKI M, NIOPAS I, LADOUKAKIS E, et al. Efficacy of flumequine administered by bath or through medicated nauplii of Artemia fransiscana (L.) in the treatment of vibriosis in sea bass larvae[J]. Aquaculture, 2010, 306(1-4): 146-152.
[6] KARUNARATHNE W A H M, MOLAGODA I M N, KIM M S, et al. Flumequine-mediated upregulation of p38 MAPK and JNK results in melanogenesis in B16F10 cells and zebrafish larvae[J]. Biomolecules, 2019, 9(10): 596.
[7] KANG J W, HOSSAIN M A, CHOI B, et al. Toxicological evaluation of flumequine in pubertal male rats after oral administration for six weeks[J]. Journal of Veterinary Research, 2018, 62(1): 87.
[8] NAVINER M, GORDON L, GIRAUD E, et al. Antimicrobial resistance of Aeromonas spp. isolated from the growth pond to the commercial product in a rainbow trout farm following a flumequine treatment[J]. Aquaculture, 2011, 315(3-4): 236-241.