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.
Flumequine是一种生物利用度良好的氟喹诺酮类抗生素，也是拓扑异构酶II的抑制剂，IC50值为15μM[1,2]。Flumequine通过抑制细菌DNA回旋酶以阻止DNA复制发挥作用[3]，通常用于家畜和鱼类肠道疾病的治疗和研究[4,5]。
在体外，Flumequine（12.5, 25, 50μM）处理小鼠黑色素瘤B16F10细胞72h，细胞外黑色素含量分别增加6.1 ± 1.6%、9.4 ± 0.5%和11.6 ± 0.3%，细胞内黑色素含量分别增加42.2 ± 3.6%、58.1 ± 1.0%和59.1 ± 0.6%。Flumequine（50μM）处理B16F10细胞48h，显著上调了小眼畸形相关转录因子（MITF）和酪氨酸酶的mRNA表达水平[6]。
在体内，Flumequine（750mg/kg; once daily）口服给予青春期雄性Wistar大鼠6周，血清白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）水平显著降低。且从给药第7天起，大鼠体重增长显著减缓，脑、肾上腺、甲状腺和睾丸的相对重量显著增加[7]。Flumequine（12mg/kg/day）通过药饲口服给予感染红嘴病的虹鳟鱼8天，治疗后24h，鱼皮肤和鱼肠道内容物中Flumequine耐药气单胞菌的比例显著升高[8]。