Reproductive Toxicities Caused by Swainsonine from Locoweed in Mice

Abstract

Swainsonine is the primary toxin in locoweeds. It causes intention tremors, reproductive dysfunction, emaciation, and death. The objective of the present study was to evaluate the potential reproductive and developmental toxicities caused by swainsonine in mice. The treatment groups consisting of three generations of mice were given a range of concentrations of swainsonine by intraperitoneal injection (2.50 mg/kg body weight (BW), 1.20 mg/kg BW, 0.60 mg/kg BW, and 0 mg/kg BW). The 0 mg/kg BW group exhibited significantly fewer estrous cycles and an increased number of estrous ones compared to the 2.50 mg/kg BW, 1.20 mg/kg BW, and 0.60 mg/kg BW groups (P < 0.05). All three generations of mice treated with swainsonine had significantly higher spleen, liver, and kidney indices and significantly lower body weights compared to the 0 mg/kg BW group (P < 0.05). For the first and second generations of treatment group, the copulation indices and the numbers of live pups on postnatal days (PND) 0, 4, and 15 were significantly decreased compared to those of the 0 mg/kg BW group (P < 0.05). The fertility and gestation indices of the treatment group of the first generation were significantly increased compared to the 2.50 mg/kg BW, 1.20 mg/kg BW, and 0.60 mg/kg BW groups of the second generation (P < 0.05). Cumulatively, these results indicate that swainsonine may cause reproductive and developmental toxicities in mice in both parents and offspring.

Future perspectives of Therapeutic Claims of an Ethnopharmacological Drug Ipomoea carnea Jacq. - A Critical Review

“…(41) Severe reproductive and developmental toxicities are associated with swainsonine poisoning. (56) However, the plant extracts has not produced death up to dose level 2000 mg/kg and did not cause any toxic effect up to dose of 3000 mg/kg in mice in acute toxicity study. (37)…”

Swainsonine Induces Liver Inflammation in Mice via Disturbance of Gut Microbiota and Bile Acid Metabolism

“…In our swainsonine intervention experiments, after acclimating in the barrier animal facility for about 1 week, 32 male mice were stochastically divided into four groups: 8 mice treated with sterilized water (control group), 8 mice treated with 0.01 mg/mL swainsonine (low group), 8 mice treated with 0.05 mg/mL swainsonine (middle group), 8 mice treated with 0.25 mg/mL swainsonine (high group). We chose 0.01, 0.05, and 0.25 mg/mL swainsonine as low, middle, and high doses, which were converted into a range of concentrations of swainsonine by gavage mice based on body weight (0.1, 0.5, and 2.5 mg/kg body weight). , The above interventions were carried out by gavage every two days and sustained for 4 weeks. All mice received normal chow diet, and the body weight and food intake were determined per week.…”

“…As alkaloid-synthesizing herbaceous legumes, locoweeds including toxic Oxytropis and Astraglus species are collectively responsible for the majority of livestock poisoning losses and seriously threaten animal husbandry on grasslands in China and the United States . Locoweeds have an impact not only on the livestock industry but also on ecology because locoweeds such as Oxytropis ochrocephala have evolved in a variety of adaptations, including drought, cold, and salt tolerance; as a result, they have replaced other plants and become dominant in the rangeland plant communities. , Swainsonine is the main toxic component of locoweed plants, and its chemical structure is shown in Figure S1, which can bring about livestock poisoning such as locoism marked by nervous system disorder. , In addition, the depression, behavior alteration, loss of weight, and even death of livestock may be caused by the ingestion of swainsonine-containing plants, and economic losses have been estimated to be tens of millions of dollars annually …”

Plant toxins: alkaloids and their toxicities

“…Swainsonine (Figure 4) is an indolizidine alkaloid isolated from Swainsona plants [25]. The swainsonine can inhibit lysosomal hydroxylases such as α-mannosidase and Golgi α-mannosidase, hence leads to the cellular alteration that can be indicated by lysosomal storage disease due to excessive carbohydrate accumulation in lysosomes [53]. Most of the swainsonine poisoning cases are caused by locoweeds species such as Astragalus spp.…”

“…The structure of swainsonine [54] According to Chenchen et al [55], ingestion of locoweeds by cattle, sheep and horses can cause the neurological condition called locoism. Apart from that, the swainsonine toxicity may also cause intention tremors, depression, nervousness, proprioceptive deficits, aberrant behavior, emaciation, reproductive dysfunction and death [53,55]. There are cases of swainsonine poisoning on animals such as a horse where the animal shows a symptom of excitement, exaggerated fright reaction, trembling and mild ataxia [56].…”