The Reproductive Toxicity of Mequindox in a Two-Generation Study in Wistar Rats

Abstract

Mequindox (MEQ), belonging to quinoxaline-di-N-oxides (QdNOs), has been extensively used as a synthetic antibacterial agent. To evaluate the reproductive toxicity of MEQ, different concentrations of MEQ were administered to Wistar rats by feeding diets containing 0, 25, 55, 110, and 275 mg/kg, respectively. Each group consisting of 25 males and 25 females (F0) was treated with different concentrations of MEQ for 12-week period time, prior to mating and during mating, gestation, parturition and lactation. At weaning, 25 males and 25 females of F1 generation weanlings per group were randomly selected as parents for the F2 generation. Selected F1 weanlings were exposed to the same diet and treatment as their parents. The number of live litter and indexes of mating and fertility were significantly decreased in the F1 and F2 generation at 110 and 275 mg/kg groups. Significant decrease in pup vitality during lactation was observed in F1 litter at 275 mg/kg group, in F2 litter at 55, 110, and 275 mg/kg groups. A downward trend in the body weights was observed in F1 pups at 55, 110, and 275 mg/kg MEQ groups, and in F2 pups at 110 and 275 mg/kg MEQ groups. The changed levels of ALT, AST, CREA, BUN, UA, Na, and K were noted in the serum of rats. The histopathologic examination showed that MEQ induced toxicity in the liver, kidney, adrenal, uterus and testis. The no-observed-adverse-effect level (NOAEL) for reproduction toxicity of MEQ was 25 mg/kg diet. The malformations and severe maternal toxicity of MEQ caused adverse effects on the conceptus and embryo, which result in fetal malformations and fetal deaths. In summary, the present study showed that MEQ induced maternal, embryo and reproductive toxicities as well as teratogenicity in rats.

Baseline and time‐updated factors in preclinical development of anionic dendrimers as successful anti‐HIV‐1 vaginal microbicides

“…Reproduction toxicity studies analyze the morphology and motility of male sperm, parturition, the number of live and dead pups, and the sex of the puppies. The same procedure is repeated to obtain the offspring of the second generation (Ganiger et al, 2007;Q. Liu et al, 2018;Montagnini et al, 2018;Wang et al, 2019).…”

“…Reproduction toxicity studies analyze the morphology and motility of male sperm, parturition, the number of live and dead pups, and the sex of the puppies. The same procedure is repeated to obtain the offspring of the second generation (Ganiger et al, 2007; Q. Liu et al, 2018; Montagnini et al, 2018; Wang et al, 2019). Neurotoxicity studies evaluate neuropathological lesions and neurological dysfunctions (loss of memory, sensory defects, and learning and memory dysfunctions) after 28 or 90 days of administration (Ishtiaq et al, 2021; Xu et al, 2021).…”

Advances in Metabolism and Metabolic Toxicology of Quinoxaline 1,4-Di-N-oxides

“…44 Studies show that MEQ could induce reproductive toxicity and teratogenicity in rat maternal and embryonic populations. 45 Metabolites of MEQ exhibit toxicity that is more severe than that of the precursor. Five metabolites (M3, 3-hydroxymethyl 1-desoxymequindox; M6, bisdesoxymequindox; M7, 3-hydroxymethyl bisdesoxymequindox; M11, 2-isoethanol 4-desoxymequindox; and M14, 2-isoethanol bisdesoxymequindox) and one metabolite (M11) were observed in the rat liver and spleen, respectively.…”

A Novel Metabolite as a Hapten to Prepare Monoclonal Antibodies for Rapid Screening of Quinoxaline Drug Residues

“…Quinoxalines (Qx) are chemically synthesized antibacterial drugs that have a strong inhibitory effect on both gram-positive and gram-negative bacteria [ 1 , 2 ]. Due to the broad antimicrobial spectrum and obvious growth-promoting effects, Qx are used in excessive amounts by farmers as feed additives to obtain more economic benefits [ 3 ]. However, several studies have shown that Qx can cause toxic side effects such as trichothecation, photosensitivity, and adrenal cortical damage in livestock and poultry.…”